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Nakabayashi M, Tanabe J, Ogura Y, Ichinose M, Shibagaki Y, Kamijo-Ikemori A, Ono Y. Correlation of diabetic renal hypoperfusion with microvascular responses of the skeletal muscle: a rat model study using diffuse correlation spectroscopy. BIOMEDICAL OPTICS EXPRESS 2024; 15:3900-3913. [PMID: 38867789 PMCID: PMC11166419 DOI: 10.1364/boe.522385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 05/10/2024] [Accepted: 05/12/2024] [Indexed: 06/14/2024]
Abstract
Using diffuse correlation spectroscopy, we assessed the renal blood flow and thigh muscle microvascular responses in a rat model of type 2 diabetes. The blood flow index at the renal surface decreased significantly with arterial clamping, cardiac extirpation, and the progression of diabetic endothelial dysfunction. Renal blood flow measured in diabetic and nondiabetic rats also showed a significant correlation with the reactive hyperemic response of the thigh muscle. These results suggest shared microcirculatory dysfunction in the kidney and skeletal muscle and support endothelial responses in the skeletal muscle as a potential noninvasive biomarker of renal hypoperfusion.
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Affiliation(s)
- Mikie Nakabayashi
- Electrical Engineering Program, Graduate School of Science and Technology, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, Kanagawa 2148571, Japan
| | - Jun Tanabe
- Division of Nephrology and hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 2168511, Japan
| | - Yuji Ogura
- Department of Physiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 2168511, Japan
| | - Masashi Ichinose
- Human Integrative Physiology Laboratory, School of Business Administration, Meiji University, 1-1 Surugadai, Kanda, Chiyoda-ku Tokyo 1018301, Japan
| | - Yugo Shibagaki
- Division of Nephrology and hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 2168511, Japan
| | - Atsuko Kamijo-Ikemori
- Division of Nephrology and hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 2168511, Japan
- Department of Anatomy, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 2168511, Japan
| | - Yumie Ono
- Department of Electronics and Bioinformatics, School of Science and Technology, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, Kanagawa 2148571, Japan
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2
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Vasudevan V, Unni SN. Skin microcirculatory responses: A potential marker for early diabetic neuropathy assessment using a low-cost portable diffuse optical spectrometry device. JOURNAL OF BIOPHOTONICS 2024; 17:e202300335. [PMID: 38116917 DOI: 10.1002/jbio.202300335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 11/05/2023] [Accepted: 11/24/2023] [Indexed: 12/21/2023]
Abstract
Diffuse optical measurement is an evolving optical modality providing a fast and portable solution for microcirculation assessment. Diffuse optics in static and dynamic modalities are combined here in a system to assess hemodynamics in skin tissues of control and diabetic subjects. The in-house developed system consists of a laser source, fiber optic probe, a low-cost avalanche photodiode, a finite element model (FEM) derived static optical property estimator, and a software correlator for continuous flow monitoring through microvasculature. The studies demonstrated that the system quantifies the changes in blood flow rate in the immediate skin subsurface. The system is calibrated with in vitro flow models and a proof-of-concept was demonstrated on a limited number of subjects in a clinical environment. The flow changes in response to vasoconstrictive and vasodilative stimuli were analyzed and used to classify different stages of diabetes, including diabetic neuropathy.
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Affiliation(s)
- Vysakh Vasudevan
- Biophotonics Lab, Department of Applied Mechanics and Biomedical Engineering, IIT Madras, Chennai, India
| | - Sujatha Narayanan Unni
- Biophotonics Lab, Department of Applied Mechanics and Biomedical Engineering, IIT Madras, Chennai, India
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3
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Ageing modifies acute resting blood pressure responses to incremental consumption of dietary nitrate: a randomised, cross-over clinical trial. Br J Nutr 2023; 129:442-453. [PMID: 35508923 DOI: 10.1017/s0007114522001337] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Beetroot (BR) is a rich source of nitrate (NO3-) that has been shown to reduce blood pressure (BP). Yet, no studies have examined the vascular benefits of BR in whole-food form and whether the effects are modified by age. This study was a four-arm, randomised, open-label, cross-over design in twenty-four healthy adults (young n 12, age 27 ± 4 years, old n 12, age 64 ± 5 years). Participants consumed whole-cooked BR at portions of (NO3- content in brackets) 100 g (272 mg), 200 g (544 mg) and 300 g (816 mg) and a 200-ml solution containing 1000 mg of potassium nitrate (KNO3) on four separate occasions over a 4-week period (≥7-d washout period). BP, plasma NO3- and nitrite (NO2-) concentrations, and post-occlusion reactive hyperaemia via laser Doppler, were measured pre- and up to 5-h post-intervention. Data were analysed by repeated-measures ANOVA. Plasma NO2- concentrations were higher in the young v. old at baseline and post-intervention (P < 0·05). All NO3- interventions decreased systolic and diastolic BP in young participants (P < 0·05), whereas only KNO3 (at 240-300 min post-intake) significantly decreased systolic (-4·8 mmHg, -3·5 %, P = 0·024) and diastolic (-5·4 mmHg, -6·5 %, P = 0·007) BP in older participants. In conclusion, incremental doses of dietary NO3- reduced systolic and diastolic BP in healthy young adults whereas in the older group a significant decrease was only observed with the highest dose. The lower plasma NO2- concentrations in older participants suggest that there may be mechanistic differences in the production of NO from dietary NO3- in young and older populations.
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Lanting S, Way K, Sabag A, Sultana R, Gerofi J, Johnson N, Baker M, Keating S, Caterson I, Twigg S, Chuter V. The Efficacy of Exercise Training for Cutaneous Microvascular Reactivity in the Foot in People with Diabetes and Obesity: Secondary Analyses from a Randomized Controlled Trial. J Clin Med 2022; 11:jcm11175018. [PMID: 36078945 PMCID: PMC9456717 DOI: 10.3390/jcm11175018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 08/11/2022] [Accepted: 08/22/2022] [Indexed: 11/16/2022] Open
Abstract
It is unclear if cutaneous microvascular dysfunction associated with diabetes and obesity can be ameliorated with exercise. We investigated the effect of 12-weeks of exercise training on cutaneous microvascular reactivity in the foot. Thirty-three inactive adults with type 2 diabetes and obesity (55% male, 56.1 ± 7.9 years, BMI: 35.8 ± 5, diabetes duration: 7.9 ± 6.3 years) were randomly allocated to 12-weeks of either (i) moderate-intensity continuous training [50−60% peak oxygen consumption (VO2peak), 30−45 min, 3 d/week], (ii) low-volume high-intensity interval training (90% VO2peak, 1−4 min, 3 d/week) or (iii) sham exercise placebo. Post-occlusive reactive hyperaemia at the hallux was determined by laser-Doppler fluxmetry. Though time to peak flux post-occlusion almost halved following moderate intensity exercise, no outcome measure reached statistical significance (p > 0.05). These secondary findings from a randomised controlled trial are the first data reporting the effect of exercise interventions on cutaneous microvascular reactivity in the foot in people with diabetes. A period of 12 weeks of moderate-intensity or low-volume high-intensity exercise may not be enough to elicit functional improvements in foot microvascular reactivity in adults with type 2 diabetes and obesity. Larger, sufficiently powered, prospective studies are necessary to determine if additional weight loss and/or higher exercise volume is required.
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Affiliation(s)
- Sean Lanting
- Faculty of Health and Medicine, School of Health Sciences, University of Newcastle, Ourimbah, NSW 2258, Australia
- Correspondence:
| | - Kimberley Way
- Faculty of Health and Medicine, Discipline of Exercise and Sports Science, University of Sydney, Camperdown, NSW 2006, Australia
- The Boden Collaboration for Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Camperdown, NSW 2006, Australia
- The Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia
| | - Angelo Sabag
- Faculty of Health and Medicine, Discipline of Exercise and Sports Science, University of Sydney, Camperdown, NSW 2006, Australia
- The Boden Collaboration for Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Camperdown, NSW 2006, Australia
- The Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia
| | - Rachelle Sultana
- Faculty of Health and Medicine, Discipline of Exercise and Sports Science, University of Sydney, Camperdown, NSW 2006, Australia
- The Boden Collaboration for Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Camperdown, NSW 2006, Australia
- The Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia
| | - James Gerofi
- The Boden Collaboration for Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Camperdown, NSW 2006, Australia
- The Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia
| | - Nathan Johnson
- Faculty of Health and Medicine, Discipline of Exercise and Sports Science, University of Sydney, Camperdown, NSW 2006, Australia
- The Boden Collaboration for Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Camperdown, NSW 2006, Australia
- The Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia
| | - Michael Baker
- School of Exercise Science, Australian Catholic University, Strathfield, NSW 2135, Australia
| | - Shelley Keating
- Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, The University of Queensland, St Lucia, QLD 4072, Australia
| | - Ian Caterson
- The Boden Collaboration for Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Camperdown, NSW 2006, Australia
- The Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia
| | - Stephen Twigg
- The Charles Perkins Centre, University of Sydney, Camperdown, NSW 2006, Australia
- School of Medicine, University of Sydney, Camperdown, NSW 2006, Australia
| | - Vivienne Chuter
- School of Health Sciences, Western Sydney University, Campbelltown, NSW 2751, Australia
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Skin microvascular function, as assessed with laser speckle contrast imaging, is impaired in untreated essential and masked hypertension. Hypertens Res 2022; 45:445-454. [PMID: 34916663 DOI: 10.1038/s41440-021-00816-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 10/26/2021] [Accepted: 11/01/2021] [Indexed: 11/08/2022]
Abstract
Skin microcirculation has been proposed as a model of generalized microvascular function. Laser speckle contrast imaging (LSCI) is a novel, noninvasive method to assess skin microvascular function (SMF). To date, SMF data in hypertension are conflicting, and no study with LSCI exists. In addition, the application of LSCI in masked hypertension is scarce. We assessed SMF with LSCI coupled with postocclusive reactive hyperemia (PORH) in patients with newly diagnosed untreated essential hypertension (UHT) and masked hypertension (MH) compared to healthy normotensive (NT) individuals. We enrolled consecutive UHT and MH patients and NT individuals matched for age, sex, body mass index, and smoking status. All participants underwent SMF assessment by LSCI coupled with PORH (PeriCam PSI system, Perimed, Sweden). Correlation analyses were performed between SMF and common cardiovascular risk factors and BP parameters. In total, 70 UHT patients, 20 MH patients and 40 NT individuals were enrolled. UHT and MH patients exhibited significantly impaired SMF compared to NT individuals (UHT patients: base-to-peak flux (p < 0.001)), PORH amplitude (p < 0.001); MH patients: base-to-peak flux (p = 0.013), PORH amplitude (p = 0.022). MH patients did not differ compared to UHT patients. SMF was negatively associated with office, ambulatory and central BP. SMF was negatively associated with blood lipids and smoking. Hypertensive status was the single most important predictor of SMF. UHT and MH patients exhibit impaired SMF compared to NT individuals. MH patients did not differ compared to UHT patients. SMF is negatively associated with BP and cardiovascular risk factors. LSCI could be implemented as a useful tool to investigate SMF in hypertension.
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6
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Lanting SM, Chan TL, Casey SL, Peterson BJ, Chuter VH. Cutaneous microvascular reactivity in Charcot neuroarthropathy: a systematic review and meta-analysis. J Foot Ankle Res 2022; 15:17. [PMID: 35232466 PMCID: PMC8886937 DOI: 10.1186/s13047-022-00522-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 02/15/2022] [Indexed: 10/30/2024] Open
Abstract
Background To systematically evaluate the literature investigating the relationship between cutaneous microvascular reactivity in the foot of adults with diabetes-related Charcot neuroarthropathy compared to a non-Charcot adult control group. Methods A systematic search was conducted to June 2021 using the biomedical databases EBSCO Megafile Ultimate, Cochrane Library and EMBASE. Original research conducting comparative investigation of cutaneous microvascular reactivity in the foot of adults with diabetes and any pattern of acute or chronic Charcot neuroarthropathy and any non-Charcot adult control groups were included. A modified Critical Appraisal Skills Programme tool was used for quality appraisal. Cutaneous microvascular reactivity in diabetes-related Charcot neuroarthropathy data were synthesised and meta-analysis conducted where possible. Results The search strategy identified 1,684 articles, with seven eligible for inclusion. Included studies used various methodologies and equipment to assess cutaneous microvascular reactivity in 553 participants (162 with Charcot neuroarthropathy). Cutaneous microvascular reactivity in Charcot neuroarthropathy groups was impaired compared to uncomplicated diabetes groups. Meta-analysis investigating the difference in response to thermal hyperaemia demonstrated a significant difference in cutaneous microvascular reactivity between Charcot neuroarthropathy and peripheral neuropathy with a large, pooled effect size (SMD 1.46 95% CI: 0.89–2.02) and low heterogeneity (I2 = 4%, T2 = 0.01) indicating that the cutaneous microvascular response is more impaired in peripheral neuropathy than in Charcot neuroarthropathy. Conclusions Charcot neuroarthropathy is associated with greater cutaneous microvascular reactivity in the periphery relative to diabetes cohorts with diabetes-related peripheral neuropathy alone. It is unknown if this occurs prior to, or as a result of, Charcot neuroarthropathy.
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Affiliation(s)
- Sean Michael Lanting
- College of Health, Medicine and Wellbeing, School of Health Sciences, University of Newcastle, Ourimbah, NSW, Australia.
| | - Tsz Long Chan
- College of Health, Medicine and Wellbeing, School of Health Sciences, University of Newcastle, Ourimbah, NSW, Australia
| | - Sarah Louise Casey
- College of Health, Medicine and Wellbeing, School of Health Sciences, University of Newcastle, Ourimbah, NSW, Australia
| | - Benjamin John Peterson
- Department of Podiatry, School of Health, Medical and Applied Sciences, CQUniversity, Rockhampton, QLD, Australia
| | - Vivienne Helaine Chuter
- College of Health, Medicine and Wellbeing, School of Health Sciences, University of Newcastle, Ourimbah, NSW, Australia.,School of Health Sciences, Western Sydney University, Campbelltown, NSW, Australia
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7
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Bönhof GJ, Sipola G, Strom A, Herder C, Strassburger K, Knebel B, Reule C, Wollmann JC, Icks A, Al-Hasani H, Roden M, Kuss O, Ziegler D. BOND study: a randomised double-blind, placebo-controlled trial over 12 months to assess the effects of benfotiamine on morphometric, neurophysiological and clinical measures in patients with type 2 diabetes with symptomatic polyneuropathy. BMJ Open 2022; 12:e057142. [PMID: 35115359 PMCID: PMC8814806 DOI: 10.1136/bmjopen-2021-057142] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION Diabetic sensorimotor polyneuropathy (DSPN) affects approximately 30% of people with diabetes, while around half of cases are symptomatic. Currently, there are only few pathogenetically oriented pharmacotherapies for DSPN, one of which is benfotiamine, a prodrug of thiamine with a high bioavailability and favourable safety profile. While benfotiamine has shown positive effects in preclinical and short-term clinical studies, no long-term clinical trials are available to demonstrate disease-modifying effects on DSPN using a comprehensive set of disease-related endpoints. METHODS AND ANALYSIS The benfotiamine on morphometric, neurophysiological and clinical measures in patients with type 2 diabetes trial is a randomised double-blind, placebo-controlled parallel group monocentric phase II clinical trial to assess the effects of treatment with benfotiamine compared with placebo in participants with type 2 diabetes and mild to moderate symptomatic DSPN. Sixty participants will be 1:1 randomised to treatment with benfotiamine 300 mg or placebo two times a day over 12 months. The primary endpoint will be the change in corneal nerve fibre length assessed by corneal confocal microscopy (CCM) after 12 months of benfotiamine treatment compared with placebo. Secondary endpoints will include other CCM measures, skin biopsy and function indices, variables from somatic and autonomic nerve function tests, clinical examination and questionnaires, general health, health-related quality of life, cost, safety and blood tests. ETHICS AND DISSEMINATION The trial was approved by the competent authority and the local independent ethics committee. Trial results will be published in peer-reviewed journals, conference abstracts, and via online and print media. TRIAL REGISTRATION NUMBER DRKS00014832.
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Affiliation(s)
- Gidon J Bönhof
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany
| | - Gundega Sipola
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Alexander Strom
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, Munich-Neuherberg, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany
| | - Klaus Strassburger
- German Center for Diabetes Research, Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Birgit Knebel
- German Center for Diabetes Research, Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | | | | | - Andrea Icks
- Institute for Health Services Research and Health Economics, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- Institute for Health Services Research and Health Economics, Centre for Health and Society, Medical Faculty and University Hospital Düsseldorf at Heinrich-Heine-University, Düsseldorf, Germany
| | - Hadi Al-Hasani
- German Center for Diabetes Research, Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany
| | - Oliver Kuss
- Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- Centre for Health and Society, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany
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8
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Maruhashi T, Higashi Y. Clinical implication of impaired skin microvascular function in patients with hypertension. Hypertens Res 2021; 45:535-537. [PMID: 34955531 DOI: 10.1038/s41440-021-00838-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 12/03/2021] [Indexed: 11/09/2022]
Affiliation(s)
- Tatsuya Maruhashi
- Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
| | - Yukihito Higashi
- Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.,Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan
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9
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Fujii N, McGarr GW, Amano T, Nishiyasu T, Sigal RJ, Kenny GP. Type 2 diabetes impairs vascular responsiveness to nitric oxide, but not the venoarteriolar reflex or post-occlusive reactive hyperaemia in forearm skin. Exp Dermatol 2021; 30:1807-1813. [PMID: 34114706 DOI: 10.1111/exd.14408] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 04/21/2021] [Accepted: 06/01/2021] [Indexed: 11/28/2022]
Abstract
The venoarteriolar reflex (VAR) is a local mechanism by which vasoconstriction is mediated in response to venous congestion. This response may minimize tissue overperfusion, preventing capillary damage and oedema. Post-occlusive reactive hyperaemia (PORH) is used to assess microvascular function by performing a brief local arterial occlusion resulting in a subsequent rapid transient vasodilation. In the current study, we hypothesized that type 2 diabetes (T2D) attenuates VAR and PORH responses in forearm skin in vivo. In 11 healthy older adults (Control, 58 ± 8 years) and 13 older adults with controlled T2D (62 ± 10 years), cutaneous blood flow measured by laser-Doppler flowmetry was monitored following a 3-min venous occlusion of 45 mm Hg that elicited the VAR, followed by a 3-min recovery period and then a 5-min arterial occlusion of 240 mm Hg that induced PORH. Finally, sodium nitroprusside, a nitric oxide donor, was administered to induce maximum vasodilation. VAR and PORH variables were similar between groups. By contrast, maximal cutaneous blood flow induced by sodium nitroprusside was lower in the T2D group. Taken together, our observations indicate that T2D impairs vascular smooth muscle responsiveness to nitric oxide, but not VAR and PORH in forearm skin.
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Affiliation(s)
- Naoto Fujii
- Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba City, Japan
| | - Gregory W McGarr
- Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada
| | - Tatsuro Amano
- Laboratory for Exercise and Environmental Physiology, Faculty of Education, Niigata University, Niigata, Japan
| | - Takeshi Nishiyasu
- Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba City, Japan
| | - Ronald J Sigal
- Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada.,Departments of Medicine, Cardiac Sciences and Community Health Sciences, Faculties of Medicine and Kinesiology, University of Calgary, Canada
| | - Glen P Kenny
- Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada
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10
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De Lorenzo A, Estato V, Castro-Faria-Neto HC, Tibirica E. Obesity-Related Inflammation and Endothelial Dysfunction in COVID-19: Impact on Disease Severity. J Inflamm Res 2021; 14:2267-2276. [PMID: 34079332 PMCID: PMC8166352 DOI: 10.2147/jir.s282710] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 05/13/2021] [Indexed: 12/13/2022] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has put into evidence another pandemic – obesity. Currently, several studies have documented the association between obesity and COVID-19 severity. The mechanisms underlying the increased risk of complications and mortality in obese patients with COVID-19 are of diverse nature. Inflammation plays a central role in obesity. Metabolic alterations seen in obese patients are related to an inflammatory response, and several studies report elevated levels of circulating inflammatory cytokines in obese patients. Also, deregulated expression of adipokines, such as leptin and resistin, increase the expression of vascular adhesion molecule 1 and intercellular adhesion molecule 1 that contribute to increased vascular leukocyte adhesiveness and additional oxidative stress. Additionally, it is now recognized that the chronic impairment of systemic vascular endothelial function in patients with cardiovascular and metabolic disorders, including obesity, when intensified by the detrimental effects of SARS-CoV-2 over the endothelium, may explain their worse outcomes in COVID-19. In fact, vascular endothelial dysfunction may contribute to a unfavorable response of the endothelium to the infection by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic environment in obesity may also provide a link to the increased cardiovascular events in these patients.
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Affiliation(s)
| | - Vanessa Estato
- Laboratorio de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brail
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11
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Sørland K, Sandvik MK, Rekeland IG, Ribu L, Småstuen MC, Mella O, Fluge Ø. Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study. Front Med (Lausanne) 2021; 8:642710. [PMID: 33829023 PMCID: PMC8019750 DOI: 10.3389/fmed.2021.642710] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 02/23/2021] [Indexed: 12/13/2022] Open
Abstract
Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide. Methods: This substudy to the open-label phase II trial "Cyclophosphamide in ME/CFS" included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18-65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls (N = 66 and N = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls (N = 30). Results: Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5-13.1, n = 35) compared to healthy individuals (median FMD 7.7%, range 0.7-21, n = 66) (p = 0.005), as was PORH with patient score median 1,331 p.u. (range 343-4,334) vs. healthy individuals 1,886 p.u. (range 808-8,158) (p = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls. Conclusions: Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.
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Affiliation(s)
- Kari Sørland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway
| | | | - Ingrid Gurvin Rekeland
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Science, Institute of Medicine, University of Bergen, Bergen, Norway
| | - Lis Ribu
- Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway
| | | | - Olav Mella
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Science, Institute of Medicine, University of Bergen, Bergen, Norway
| | - Øystein Fluge
- Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Science, Institute of Medicine, University of Bergen, Bergen, Norway
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12
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Degree of adiposity and obesity severity is associated with cutaneous microvascular dysfunction in type 2 diabetes. Microvasc Res 2021; 136:104149. [PMID: 33647342 DOI: 10.1016/j.mvr.2021.104149] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/24/2021] [Accepted: 02/21/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUNDS AND AIMS Obesity and diabetes independently contribute to cutaneous microvascular dysfunction via pathological processes that are not fully understood. We sought to determine if obesity severity is associated with cutaneous microvascular dysfunction and measures of peripheral arterial disease in adults with type 2 diabetes in cross-sectional observational study design. METHODS AND RESULTS Primary outcomes were post-occlusive reactive hyperaemia as determined by laser-Doppler fluxmetry (peak flux post-occlusion, time to peak flux post-occlusion, peak as a percentage of baseline, and area under the curve [AuC] index post-occlusion to pre-occlusion). Secondary outcomes were ankle- and toe-brachial indices (ABI and TBI) and systolic toe pressure. Thirty-six participants (20 men, 16 women) with mean age 55 ± 8 years, BMI of 36 ± 5 kg/m2 and duration of diabetes 8 ± 6 years underwent measurements. After adjusting for age and duration of diabetes, SAT and total percentage body fat were able to explain 29% (p = 0.001) and 20% (p = 0.01) of variance of AuC index models, as well as 29% (p = 0.02) and 18% (p = 0.02) of peak as a percentage of baseline models, respectively. Though TBI demonstrated moderate, significant correlations with SAT (r:0.37, p = 0.04) and total percentage body fat (r:0.39, p = 0.03), these were not upheld by regression analyses. Neither ABI nor systolic toe pressure significantly correlated with any measure of adiposity or obesity. CONCLUSION These findings demonstrate impairment in cutaneous microvascular function related to adiposity and obesity severity in adults with type 2 diabetes, suggesting that obesity may pathologically effect cutaneous microvascular function in the absence of overt macrovascular disease, warranting further investigation.
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13
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Lindstedt S, Wlosinska M, Nilsson AC, Hlebowicz J, Fakhro M, Sheikh R. Successful improved peripheral tissue perfusion was seen in patients with atherosclerosis after 12 months of treatment with aged garlic extract. Int Wound J 2021; 18:681-691. [PMID: 33590955 PMCID: PMC8450802 DOI: 10.1111/iwj.13570] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 02/01/2021] [Indexed: 12/30/2022] Open
Abstract
Patients with arteriolosclerosis have impaired microvascular perfusion leading to impaired wound healing. Aged garlic extract has shown to have a positive impact on vascular elasticity. The present study aimed to assess the effect of long‐term treatment with AGE on peripheral tissue perfusion in patients with confirmed atherosclerosis. Ninety three patients with a CT‐scan confirmed coronary artery arteriolosclerosis were randomised in a double‐blind manner to placebo or 2400 mg AGE daily for 1 year. Peripheral tissue perfusion was evaluated at 0‐ and 12‐months using Laser Speckle Contrast Imaging. Measurement of post occlusive reactive hyperemia (PORH) and cutaneous vascular conductance (CVC) using acetylcholine iontophoresis (Ach) was conducted. After 12 months a significant increase of 21.6% (95% CI 3.2%‐40.0%, P < .05) was seen in the relative change of PORH in the AGE compared with the placebo group. The same response was seen for CVC and Ach with an increase of 21.4% (95% CI 3.4%‐39.4%, P < .05) in the AGE group compared with the placebo group. Aged garlic extract regenerated peripheral tissue perfusion and increase microcirculation in patients with arteriolosclerosis. Adequate peripheral tissue perfusion and tissue oxygen tension are important prerequisites for successful tissue repair. Restored microcirculation in patients could hypothetically facilitate wound healing.
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Affiliation(s)
- Sandra Lindstedt
- Department of Cardiothoracic Surgery and Transplantation, Clinical Science, Lund University, Skane University Hospital, Lund, Sweden
| | - Martiné Wlosinska
- Department of Cardiothoracic Surgery and Transplantation, Clinical Science, Lund University, Skane University Hospital, Lund, Sweden
| | - Ann-Christin Nilsson
- Department of Cardiothoracic Surgery and Transplantation, Clinical Science, Lund University, Skane University Hospital, Lund, Sweden
| | - Joanna Hlebowicz
- Department of Cardiology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden
| | - Mohammed Fakhro
- Department of Cardiothoracic Surgery and Transplantation, Clinical Science, Lund University, Skane University Hospital, Lund, Sweden
| | - Rafi Sheikh
- Department of Ophthalmology, Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden
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14
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Shirazi BR, Valentine RJ, Lang JA. Reproducibility and normalization of reactive hyperemia using laser speckle contrast imaging. PLoS One 2021; 16:e0244795. [PMID: 33412561 PMCID: PMC7790538 DOI: 10.1371/journal.pone.0244795] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 12/16/2020] [Indexed: 12/27/2022] Open
Abstract
Background Impaired perfusion indices signal potential microvascular dysfunction preceding atherosclerosis and other cardiometabolic pathologies. Post-occlusive reactive hyperemia (PORH), a vasodilatory response following a mechanically induced ischemia, is a transient increase in perfusion and can assess microvascular function. The greatest blood flow change corresponding to the first minute of hyperemia (represented by time-to-peak, hyperemic velocity, AUC within 1st min) has been shown to indicate microvascular dysfunction. However, the reproducibility of these temporal kinetic indices of the PORH response is unknown. Our aim was to examine the inter- and intra-day reproducibility and standardization of reactive hyperemia, with emphasis on the kinetic indices of PORH, using laser speckle contrast imaging (LSCI) technique. Methods and results Seventeen healthy adults (age = 24 ± 3 years) completed three PORH bouts over two lab visits. LSCI region of interest was a standardized 10 cm region on the dominant ventral forearm. A 5-min brachial artery occlusion period induced by inflating an arm cuff to 200 mmHg, preceded a 4-min hyperemic period. Inter- and intra-day reliability and reproducibility of cutaneous vascular conductance (LSCI flux / mean arterial pressure) were determined using intraclass correlation (ICC) and coefficient of variation (CV%). Maximal flow and area under the curve standardized to zero perfusion showed intra- and inter-day reliability (ICC > 0.70). Time to maximal flow (TMF) was not reproducible (inter-day CV = 18%). However, alternative kinetic indices such as 1-min AUC and overshoot rate-of-change (ORC), represented as a piecewise function (at 5s, 10s, 15s, and 20s into hyperemia), were reproducible (CV< 11%). Biological zero was a reliable normalization point. Conclusion PORH measured with LSCI is a reliable assessment of microvascular function. However, TMF or its derived hyperemic velocity are not recommended for longitudinal assessment. Piecewise ORC and 1-min AUC are reliable alternatives to assess the kinetic response of PORH.
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Affiliation(s)
| | - Rudy J. Valentine
- Department of Kinesiology, Iowa State University, Ames, Iowa, United States of America
| | - James A. Lang
- Department of Kinesiology, Iowa State University, Ames, Iowa, United States of America
- * E-mail:
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15
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Hoong CWS, Tan MLS, Kao SL, Khoo EYH. Effects of external counter-pulsation on endothelial function assessed by peripheral artery tonometry, levels of glycaemia and metabolic markers in individuals with type 2 diabetes mellitus. Diabetes Metab Syndr 2020; 14:2139-2145. [PMID: 33334725 DOI: 10.1016/j.dsx.2020.11.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 10/13/2020] [Accepted: 11/03/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND AIMS External counter-pulsation (ECP) generates sheer stress thereby improving endothelial function and anginal symptoms in coronary artery disease. Endothelial dysfunction is also involved in the pathogenesis of T2DM. The aim of this pilot study was to investigate the use of ECP at different doses in improving endothelial function and glycaemic markers in T2DM. METHODS This prospective study involved 46 subjects with T2DM randomly assigned to receive 35 sessions of ECP at different regimens (0.5 h versus 1 h) and duration (7 versus 12 weeks). Endothelial function was evaluated by reactive hyperaemia index (RHI) via peripheral arterial tonometry at the start, midpoint and end of study. Other secondary outcomes included fasting glucose, HOMA-IR, HbA1c, blood pressure, lipid profile, weight and vibration sense. RESULTS There was no change in RHI across all 3 regimens of ECP individually or collectively at the end of the study (ΔRHI +0.01%, p = 0.458). Glycaemic markers also remained unchanged at endpoint. Subgroup analysis showed an improvement in RHI (ΔRHI +20.6%, p = 0.0178) in subjects with more severe endothelial dysfunction at baseline. CONCLUSION ECP did not show a beneficial effect on endothelial function or glycemic control in this South-East Asian population with T2DM at any of the three regimens. This may partly be explained by less severe endothelial dysfunction and less insulin resistance in our population at baseline.
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Affiliation(s)
| | - Maudrene Luor Shyuan Tan
- Division of Endocrinology, University Medicine Cluster, National University Health System, Singapore, Singapore
| | - Shih Ling Kao
- Division of Endocrinology, University Medicine Cluster, National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Eric Yin Hao Khoo
- Division of Endocrinology, University Medicine Cluster, National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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16
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Okamoto T, Hatakeyama S, Ando M, Songee J, Imai A, Hamano I, Fujita N, Okamoto A, Yamamoto H, Yoneyama T, Yoneyama T, Hashimoto Y, Ohyama C. The impact of microalbuminuria on overactive bladders: Results from a community-based four-year longitudinal study in Japan. Neurourol Urodyn 2020; 39:1567-1575. [PMID: 32460389 DOI: 10.1002/nau.24405] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 05/14/2020] [Indexed: 11/05/2022]
Abstract
AIMS To investigate the longitudinal association of microalbuminuria with overactive bladder (OAB). METHODS This longitudinal study investigated 561 participants of the Iwaki Health Promotion Project in both 2015 and 2019 in Japan. Microalbuminuria and OAB symptoms were assessed using the urine albuminuria creatinine ratio (ACR) and the overactive bladder symptom score (OABSS), respectively. Urine ACR was defined as high if ≥9.3 mg/gCr. Differences in OABSS between 2015 and 2019 were evaluated as ∆OABSS. Participants were divided into two groups according to ΔOABSS: high (ΔOABSS > 1) and control (≤1). We used baseline data acquired in 2015, such as urine ACR, the Pittsburgh Sleep Quality Index (PSQI), and arterial stiffness expressed by brachial-ankle pulse wave velocity (baPWV). Predictive factors of a ΔOABSS > 1 were assessed by multivariable logistic regression analysis. RESULTS This study included 332 women and 229 men. Of those, 86 (34 males and 52 females) were classified into the ΔOABSS > 1 group. There were significant group differences in age, renal function, and hemoglobin A1c. Participants in the ΔOABSS > 1 had a higher prevalence of PSQI > 5, baPWV ≥ 1400 seconds/cm, and urine ACR ≥ 9.3 mg/gCr (49% vs 20%, P = .001) than those in the control group. Multivariable analysis revealed that PSQI > 5 (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.15-4.60; P = .002) and urine ACR ≥ 9.3 mg/gCr (OR, 1.93; 95% CI, 1.15-3.23; P = .013) were independent risk factors for ΔOABSS > 1. CONCLUSIONS Microalbuminuria may be an independent risk indicator for OAB symptom exacerbation.
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Affiliation(s)
- Teppei Okamoto
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Shingo Hatakeyama
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Masataka Ando
- Department of Diet and Health Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Jung Songee
- Department of Health and Beauty Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Atsushi Imai
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Itsuto Hamano
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Naoki Fujita
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Akiko Okamoto
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hayato Yamamoto
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Tohru Yoneyama
- Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Takahiro Yoneyama
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Yasuhiro Hashimoto
- Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Chikara Ohyama
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.,Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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17
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Rodriguez-Miguelez P, Looney J, Thomas J, Harshfield G, Pollock JS, Harris RA. Sirt1 during childhood is associated with microvascular function later in life. Am J Physiol Heart Circ Physiol 2020; 318:H1371-H1378. [PMID: 32330091 DOI: 10.1152/ajpheart.00024.2020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Microvascular dysfunction often precedes other age-related macrovascular conditions and predicts future cardiovascular risk. Sirtuin 1 (Sirt1) has recently emerged as a protein that protects the vasculature and reduces the risk of cardiovascular diseases. We tested the hypothesis that lower Sirt1 during childhood is associated with a reduced microvascular function during adulthood. Thirty-four adults (34 ± 3 yr) from the Augusta Heart Study returned to participate in the present clinical observational study. Sirt1 was assessed in samples collected during both adulthood and participants' childhood (16 ± 3 yr), and data were divided based on childhood Sirt1 concentrations: <3 ng/dL (LowCS; n = 16) and ≥3 ng/dL (HighCS; n = 18). MVF was evaluated in all of the adults using laser-Doppler flowmetry coupled with three vascular reactivity tests: 1) local thermal hyperemia (LTH), 2) post-occlusive reactive hyperemia (PORH), and 3) iontophoresis of acetylcholine (ACh). The hyperemic response to LTH was significantly (P ≤ 0.044) lower in the LowCS than in the HighCS group. Similarly, the LowCS also exhibited an ameliorated (P ≤ 0.045) response to the PORH test and lower (P ≤ 0.008) vasodilation in response to iontophoresis of ACh when compared with the HighCS. Positive relationships were identified between childhood Sirt1 and all MVF reactivity tests (r≥0.367, P ≤ 0.004). Novel observations suggest that lower Sirt1 during childhood is associated with premature microvascular dysfunction in adulthood. These findings provide evidence that Sirt1 may play a critical role in microvascular function and have therapeutic potential for the prevention of age-associated vascular dysfunction in humans.NEW & NOTEWORTHY With a longitudinal cohort, novel observations from the present study demonstrate that individuals who had lower Sirt1 early in life exhibit premature microvascular dysfunction during adulthood and may be at higher risk to develop CVD. These results provide experimental evidence that Sirt1 may play an important role in microvascular function with age and represent a potential therapeutic target to prevent premature vascular dysfunction.
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Affiliation(s)
- Paula Rodriguez-Miguelez
- Department of Kinesiology and Health Sciences, Virginia Commonwealth University, Richmond, Virginia.,Georgia Prevention Institute, Augusta University, Augusta, Georgia
| | - Jacob Looney
- Georgia Prevention Institute, Augusta University, Augusta, Georgia
| | - Jeffrey Thomas
- Georgia Prevention Institute, Augusta University, Augusta, Georgia
| | | | - Jennifer S Pollock
- Georgia Prevention Institute, Augusta University, Augusta, Georgia.,Cardio-Renal Physiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Ryan A Harris
- Georgia Prevention Institute, Augusta University, Augusta, Georgia.,Sport and Exercise Science Research Institute, University of Ulster, Jordanstown, United Kingdom
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18
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Tóth-Szűki V, Bari F, Domoki F. Stable laser-Doppler flow-motion patterns in the human cutaneous microcirculation: Implications for prospective geroscience studies. Physiol Int 2020; 107:134-144. [DOI: 10.1556/2060.2020.00013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 02/25/2020] [Indexed: 11/19/2022]
Abstract
AbstractMicrovascular function has been assessed by determining the rhythmic oscillations in blood flow induced by the vasomotion of resistance vessels. Although laser-Doppler flowmetry (LDF) allows simple, non-invasive evaluation of this flow-motion in the cutaneous microcirculation, the temporal and spatial reproducibility of such assessments remains unclear.In the present study, we investigated cutaneous flow-motion in three consecutive years in eight skin regions using LDF in six healthy young volunteers. The characteristic flow-motion frequency was determined using fast-Fourier transformation. Additionally, in two years a more traditional measure of microvascular reactivity, postocclusive reactive hyperemia (PORH) was evoked in the forearm after transient brachial artery occlusion (1–2–3 min) induced by cuff inflation.Well-defined flow-motion was found in six regions showing significant differences in frequency: the highest flow-motion frequency was found in the frontal and temporal regions (8.0 ± 1.1 and 8.5 ± 1.0 cycles/min, cpm, respectively, mean ± SD) followed by the scapular, infraclavicular and coxal regions (7.5 ± 1.3; 6.7 ± 1.1 and 6.5 ± 1.2 cpm, respectively). The lowest, stable flow-motion was found in the posterior femoral region (5.5 ± 1.0 cpm), whereas flow-motion was detectable only sporadically in the limbs. The region-dependent flow-motion frequencies were very stable within individuals either between the body sides, or among the three measurements, only the infraclavicular region showed a small difference (114 ± 17%∗, % of value in 1st year; ∗P < 0.05). However, PORH indices differed after 2–3 min occlusions significantly in consecutive years.We report that flow-motion frequencies determined from LDF signals show both region-specificity and excellent intra-individual temporal and spatial reproducibility suggesting their usefulness for non-invasive follow-up of microvascular reactivity.
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Affiliation(s)
- V. Tóth-Szűki
- 1Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - F. Bari
- 2Department of Medical Physics and Informatics, Faculty of Medicine, University of Szeged, Szeged, Hungary
| | - F. Domoki
- 1Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
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Fabregate-Fuente M, Arbeitman CR, Cymberknop LJ, Bara-Ledesma N, Arriazu-Galindo M, Martin-Fernandez L, Armentano RL, Saban-Ruiz J. Characterization of Microvascular Post Occlusive Hyperemia Using Laser Doppler Flowmetry Technique in Subjects With Cardiometabolic Disorders. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2020; 2019:514-517. [PMID: 31945950 DOI: 10.1109/embc.2019.8856623] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
INTRODUCTION Laser Doppler flowmetry (LDF) provides a noninvasive real-time quantification of relative changes in cutaneous perfusion. Assessment of the microvascular function can provide information on the development of various cardiometabolic disorders. In recent years, non-invasive measurements have gain attention, due to the potential complications associated to invasive procedures. OBJECTIVE To differentiate the microvascular function between subjects with cardiometabolic disorders and healthy controls. METHODS Evaluation through LDF during post-occlusive reactive hyperemia (PORH) in patients with or without history of cardiometabolic disorders. RESULTS Peak values of microvascular flow during post-occlusive reactive hyperemia and both upload and recovery slopes were lesser in the pathological group. CONCLUSION A novel approach to characterize LDF during PORH was useful to differentiate patients with cardiometabolic disorders from healthy subjects.
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20
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Williams J, Gilchrist M, Strain D, Fraser D, Shore A. The systemic microcirculation in dialysis populations. Microcirculation 2020; 27:e12613. [PMID: 32065681 DOI: 10.1111/micc.12613] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 02/08/2020] [Accepted: 02/14/2020] [Indexed: 12/17/2022]
Abstract
In a rapidly expanding population of patients with chronic kidney disease, including 2 million people requiring renal replacement therapy, cardiovascular mortality is 15 times greater than the general population. In addition to traditional cardiovascular risk factors, more poorly defined risks related to uremia and its treatments appear to contribute to this exaggerated risk. In this context, the microcirculation may play an important early role in cardiovascular disease associated with chronic kidney disease. Experimentally, the uremic environment and dialysis have been linked to multiple pathways causing microvascular dysfunction. Coronary microvascular dysfunction is reflected in remote and more easily studied vascular beds such as the skin. There is increasing evidence for a correlation between systemic microvascular dysfunction and adverse cardiovascular outcomes. Systemic microcirculatory changes have not been extensively investigated across the spectrum of chronic kidney disease. Recent advances in non-invasive techniques studying the microcirculation in vivo in man are increasing the data available particularly in patients on hemodialysis. Here, we review current knowledge of the systemic microcirculation in dialysis populations, explore whether non-invasive techniques to study its function could be used to detect early stage cardiovascular disease, address challenges faced in studying this patient cohort and identify potential future avenues for research.
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Affiliation(s)
- Jennifer Williams
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.,NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Foundation NHS Trust, Exeter, UK
| | - Mark Gilchrist
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.,NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Foundation NHS Trust, Exeter, UK
| | - David Strain
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.,NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Foundation NHS Trust, Exeter, UK
| | - Donald Fraser
- Wales Kidney Research Unit, Cardiff University, Cardiff, UK
| | - Angela Shore
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.,NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Foundation NHS Trust, Exeter, UK
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21
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Balasubramanian G, Vas P, Chockalingam N, Naemi R. A Synoptic Overview of Neurovascular Interactions in the Foot. Front Endocrinol (Lausanne) 2020; 11:308. [PMID: 32528410 PMCID: PMC7256167 DOI: 10.3389/fendo.2020.00308] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 04/22/2020] [Indexed: 12/13/2022] Open
Abstract
Diabetes is a worldwide public health concern as it is associated with various complications. One of the major complications of diabetes is diabetic foot syndrome that results in catastrophic events such as ulceration and amputation. Therefore, the main four strategies of diabetic foot care involve risk prediction, prevention, and early diagnosis and prompt intervention. The drivers of ulceration are multifactorial, and importantly, include microcirculatory changes in the diabetic skin. Cutaneous microcirculation on the foot is greatly influenced by the small fibers which mediate thermal sensation and pain perception in addition to sympathetic activities such as thermoregulation and vasodilation. The interdependence between the neurovascular elements means with the loss of small fiber functions, the corresponding microcirculatory responses may be compromised. Thus, it can be hypothesized that the impairment of the microcirculation may follow the order of the corresponding small fiber nerve dysfunction or vice versa. In this review, select neurovascular investigations that inform the cutaneous microcirculatory and small fiber nerve function in response to pain, cold, and heat and pressure stimuli are reviewed and discussed in this order of sensory loss: the loss of pain, cold, warmth, touch and deep pressure sensation. We also discuss the neurological and vascular characteristics of each of these neurovascular responses. This review highlights the influence of small fibers on cutaneous microcirculation and the need for prospective studies that can determine the course of microcirculatory impairment over time. This, in turn, may help clarify the exact role of microcirculatory changes in the pathway of ulceration. The insights from this review can be pertinent to understand key microcirculatory disturbances and given that the microcirculatory impairment develops at an early stage, relevant interventions can be implemented to possibly reverse or regress the course of the disease. Therefore, knowledge of the neurovascular interactions aids to map the disease progression for early diagnosis and prevention of adverse complications.
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Affiliation(s)
- Gayathri Balasubramanian
- Centre for Biomechanics and Rehabilitation Technologies, Science Centre, Staffordshire University, Stoke-on-Trent, United Kingdom
| | - Prashanth Vas
- King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Nachiappan Chockalingam
- Centre for Biomechanics and Rehabilitation Technologies, Science Centre, Staffordshire University, Stoke-on-Trent, United Kingdom
- Faculty of Health Sciences, University of Malta, Msida, Malta
| | - Roozbeh Naemi
- Centre for Biomechanics and Rehabilitation Technologies, Science Centre, Staffordshire University, Stoke-on-Trent, United Kingdom
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22
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Henni S, Hersant J, Loufrani L, Duval G, Humeau-Heurtier A, Riou J, Abraham P. Painless local pressure application to test microvascular reactivity to ischemia. Microvasc Res 2018; 122:13-21. [PMID: 30399363 DOI: 10.1016/j.mvr.2018.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 10/26/2018] [Accepted: 10/29/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND Forearm cutaneous blood flux (CBF) measurement with post-occlusive reactive hyperemia (PORH) is uncomfortable and may not be devoid of risks. We aimed to investigate post-compression reactive hyperemia (PCRH) with a custom-made indenter that was designed to be easily used routinely by inexperienced observers. METHODS Medical students evaluated PCRH with 1- to 4-min pressure applications of 16 to 34 kPa and PORH with 3-min forearm cuff occlusion using laser speckle contrast imaging in 15 healthy volunteers. Participants were asked to quantify their discomfort with a visual analogue scale (VAS) of 10 cm. Total ischemia (ISCH) was quantified by the product of CBF during ischemia and ischemia duration (min). We subtracted the CBF changes in the skin from a reference ipsilateral (PCRH) or contralateral (PORH) non-stimulated area. RESULTS The average VAS was 1.0 for PCRH vs. 6.0 for PORH (p < 0.001). A strong linear relationship between ISCH and peak PCRH (r2 = 0.915, p < 0.001) was noted. Peak PORH values (63.9 laser perfusion units (LPU)) were significantly lower than all values of the 3-min PCRH (72.6 LPU), including the one obtained with 16 kPa. CONCLUSION Inexperienced observers could test microvascular reactivity with PCRH without inducing the discomfort that is typically experienced with PORH. Further, PCRH elicits a higher peak response to ischemia compared with PORH. This extremely simple method could influence a broad spectrum of routine cutaneous microcirculation investigations, especially when a painful approach is particularly inadequate or if the patient is fragile. CLINICAL TRIAL REGISTRATION NCT02861924.
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Affiliation(s)
- Samir Henni
- Vascular Medicine, University Hospital of Angers, France; MitoVasc Institute, UMR CNRS 6015 - INSERM U 1083, Faculté de Médecine, Angers, France
| | - Jeanne Hersant
- Vascular Medicine, University Hospital of Angers, France; MitoVasc Institute, UMR CNRS 6015 - INSERM U 1083, Faculté de Médecine, Angers, France
| | - Laurent Loufrani
- MitoVasc Institute, UMR CNRS 6015 - INSERM U 1083, Faculté de Médecine, Angers, France
| | - Guillaume Duval
- Department of Gerontology, University Hospital of Angers, France
| | - Anne Humeau-Heurtier
- Université Angers, LARIS - Laboratoire Angevin de Recherche en Ingénierie des Systèmes, Angers, France
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- Vascular Medicine, University Hospital of Angers, France
| | - Jeremie Riou
- UMR Inserm 1066 - CNRS 6021, Faculté de Médecine, Angers, France
| | - Pierre Abraham
- MitoVasc Institute, UMR CNRS 6015 - INSERM U 1083, Faculté de Médecine, Angers, France; Sports Medicine, University Hospital of Angers, France.
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Davies T, Gilbert-Kawai E, Wythe S, Meale P, Mythen M, Levett D, Mitchell K, Grocott M, Clough G, Martin D. Sustained vasomotor control of skin microcirculation in Sherpas versus altitude-naive lowlanders: Experimental evidence from Xtreme Everest 2. Exp Physiol 2018; 103:1494-1504. [PMID: 30182473 DOI: 10.1113/ep087236] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 08/21/2018] [Indexed: 12/20/2022]
Abstract
NEW FINDINGS What is the central question of this study? Do Sherpa highlanders, when exposed to graded hypobaric hypoxia, exhibit enhanced vasomotor and neurovascular control to maintain microcirculatory flux, and thus tissue oxygenation, when compared with altitude-naive lowlanders? What is the main finding and its importance? Sherpas, when exposed to hypobaric hypoxia at high altitude, demonstrated superior preservation of their peripheral microcirculatory perfusion, a greater oxygen unloading rate and sustained microvascular reactivity with enhanced vasomotion, when compared with altitude-naive lowlanders. These differences have not been reported previously and may improve our understanding of the multifactorial responses to sustained environmental hypoxia. ABSTRACT Enhanced oxygen delivery, consequent to an increased microvascular perfusion, has been postulated to play a key role in the physiological adaptation of Tibetan highlanders to the hypobaric hypoxia encountered at high altitude. We tested the hypothesis that Sherpas, when exposed to graded hypobaric hypoxia, demonstrate enhanced vasomotor and neurovascular control to maintain microcirculatory flux, and thus tissue oxygenation, when compared with altitude-naive lowlanders. Eighty-three lowlanders [39 men and 44 women, 38.8 (13.1) years old; mean (SD)] and 61 Sherpas [28 men and 33 women, 27.9 (6.9) years old] were studied on ascent to Everest Base Camp over 11 days. Skin blood flux and tissue oxygen saturation were measured simultaneously using combined laser Doppler fluximetry and white light spectroscopy at baseline, 3500 and 5300 m. In both cohorts, ascent resulted in a decline in the sympathetically mediated microvascular constrictor response (P < 0.001), which was more marked in lowlanders than in Sherpas (P < 0.001). The microvascular dilator response evaluated by postocclusive reactive hyperaemia was significantly greater in Sherpas than in lowlanders at all sites (P < 0.002). Spectral analysis of the blood flux signals revealed enhanced myogenic (vasomotion) activity in Sherpas, which was unaffected by ascent to 5300 m. Although skin tissue oxygenation was lower in Sherpas than in lowlanders, the oxygen unloading rate was faster, and deoxyhaemoglobin levels higher, at all altitudes. Together, these data suggest that Sherpas, when exposed to hypobaric hypoxia, demonstrated superior preservation of peripheral microcirculatory perfusion compared with altitude-naive lowlanders. The physiological differences in local microvasculature vasomotor and neurovascular control may play a key role in Sherpa adaptation to high-altitude hypobaric hypoxia by sustaining local perfusion and tissue oxygenation.
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Affiliation(s)
- Thomas Davies
- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK
| | - Edward Gilbert-Kawai
- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK
| | - Stephen Wythe
- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK
| | - Paula Meale
- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK
| | - Monty Mythen
- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK
| | - Denny Levett
- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK.,Faculty of Medicine (CES) and Institute for Life Science, University of Southampton, Southampton, UK.,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.,Centre for Human Integrative Physiology, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Kay Mitchell
- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK
| | - Michael Grocott
- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK.,Faculty of Medicine (CES) and Institute for Life Science, University of Southampton, Southampton, UK.,NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.,Centre for Human Integrative Physiology, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Geraldine Clough
- Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Daniel Martin
- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK.,Critical Care Unit, Royal Free Hospital, London, UK
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- University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK
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24
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Ono Y, Esaki K, Takahashi Y, Nakabayashi M, Ichinose M, Lee K. Muscular blood flow responses as an early predictor of the severity of diabetic neuropathy at a later stage in streptozotocin-induced type I diabetic rats: a diffuse correlation spectroscopy study. BIOMEDICAL OPTICS EXPRESS 2018; 9:4539-4551. [PMID: 30615744 PMCID: PMC6157794 DOI: 10.1364/boe.9.004539] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Revised: 08/10/2018] [Accepted: 08/16/2018] [Indexed: 06/09/2023]
Abstract
We propose a novel application of diffuse correlation spectroscopy to evaluate microvascular malfunctions of muscle tissue affected by hyperglycemia and determine their correlation with the severity of diabetic neuropathy at a later stage. Microvascular responses of the thigh muscle and the mechanical pain threshold of the hind paw of streptozotocin-induced type I diabetic rats were continuously monitored once per week for 70 days. Significantly decreased baseline blood flow and reactive hyperemia responses were observed as early as 1 week after hyperglycemia induction. The reactive hyperemia response at 2 weeks of hyperglycemia was highly correlated with the mechanical pain threshold at 8 weeks, at which time a decreased pain threshold was statistically confirmed in hyperglycemic rats relative to controls.
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Affiliation(s)
- Yumie Ono
- Department of Electronics and Bioinformatics, School of Science and Technology, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, Kanagawa 2148571, Japan
| | - Kimiya Esaki
- Electrical Engineering Program, Graduate School of Science and Technology, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, Kanagawa 2148571, Japan
| | - Yuta Takahashi
- Electrical Engineering Program, Graduate School of Science and Technology, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, Kanagawa 2148571, Japan
| | - Mikie Nakabayashi
- Department of Electronics and Bioinformatics, School of Science and Technology, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, Kanagawa 2148571, Japan
- Electrical Engineering Program, Graduate School of Science and Technology, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, Kanagawa 2148571, Japan
| | - Masashi Ichinose
- Human Integrative Physiology Laboratory, School of Business Administration, Meiji University, 1-1 Surugadai, Kanda, Chiyoda-ku, Tokyo 1018301, Japan
| | - Kijoon Lee
- College of Transdisciplinary Studies, Daegu Gyeongbuk Institute of Science and Technology, 333 Techno Jungang-daero, Hyeonpung-myeon, Dalseong-gun, Daegu, South Korea
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25
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Gandecka A, Araszkiewicz A, Piłaciński S, Wierusz-Wysocka B, Zozulińska-Ziółkiewicz D. The relationship between sudomotor function and skin microvascular reactivity in individuals with type 1 diabetes of long duration. Microvasc Res 2018; 120:84-89. [PMID: 30044961 DOI: 10.1016/j.mvr.2018.07.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Revised: 06/10/2018] [Accepted: 07/19/2018] [Indexed: 01/19/2023]
Abstract
AIM The aim of this study was to assess the relationship between sudomotor function and microvascular perfusion in patients with type 1 diabetes (DM1). METHODS We evaluated 415 patients (206 women), with DM1, median age of 41 (IQR: 33-53) years, disease duration of 25 (IQR: 20-32) years. We assessed metabolic control of diabetes and the presence of peripheral and cardiac autonomic neuropathy. Sudomotor function was assessed using Sudoscan device by electrochemical skin conductance (ESC). Microvascular function was measured by laser-Doppler flowmetry with basal perfusion, the peak flow after occlusion (PORHpeak) and THmax which is the percentage change between basal perfusion and the peak flow during thermal hyperemia (TH). The accumulation of advanced glycation end products in the skin was assessed by skin autofluorescence (AF) measurement using AGE Reader. We subdivided patients based on the presence of diabetic peripheral neuropathy (DPN), cardiac autonomic neuropathy (CAN) and according to normal value of ESC. RESULTS Patients with abnormal ESC had higher skin AF [2.5 (2.1-2.9) vs 2.1 (1.9-2.5) AU, p < 0.001], lower eGFR [83 (72-96) vs 98 (86-108) ml/min/1.73 m2, p < 0.001], higher basal perfusion [25 (12-81) vs 14 (7-43) PU, p < 0.001], lower THmax [664 (137-1461) vs 1115 (346-1933) %, p = 0.002], higher PORHpeak [104 (59-167) vs 70 (48-135) PU, p < 0.001] as compared to subjects with normal ESC results. We found negative correlation between THmax and TG level (Rs = -0.14, p < 0.005), AF (Rs = -0.19, p = 0.001), vibration perception threshold - VPT (Rs = -0.24, p < 0.001) and positive correlation with HDL level (Rs = 0.14, p = 0.005), Feet ESC (Rs = 0.21, p < 0.001) and Hands ESC (Rs = 0.14, p = 0.004). We found positive correlation between PORHpeak and TG level (Rs = 0.14, p = 0.003), skin AF (Rs = 0.29, p < 0.001), VPT (0.27, p < 0.001) and negative correlation with eGFR (Rs = -0.2, p < 0.001), HDL (Rs = -0.12, p = 0.01), Feet ESC (Rs = -0.27, p < 0.001) and Hand ESC (Rs = -0.16, p = 0.002). CONCLUSION Impaired microvascular reactivity is associated with sudomotor dysfunction in patients with type 1 diabetes.
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26
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Birkhoff W, de Vries J, Dent G, Verma A, Kerkhoffs J, van Meurs A, de Kam M, Moerland M, Burggraaf J. Retinal microcirculation imaging in sickle cell disease patients. Microvasc Res 2018; 116:1-5. [DOI: 10.1016/j.mvr.2017.09.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 09/05/2017] [Accepted: 09/05/2017] [Indexed: 01/24/2023]
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Reproducibility and agreement of different non-invasive methods of endothelial function assessment. Microvasc Res 2018; 117:50-56. [PMID: 29338981 DOI: 10.1016/j.mvr.2018.01.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Revised: 01/09/2018] [Accepted: 01/09/2018] [Indexed: 11/21/2022]
Abstract
Flow-mediated dilatation (FMD) is an established, but investigator-demanding method, used to non-invasively determine nitric oxide (NO)-dependent endothelial function in humans. Local thermal hyperemia (LTH) or post-occlusive reactive hyperemia (PORH) of the skin measured with a laser Doppler flow imager may be a less demanding alternative of FMD. We investigated the reproducibility of the different measures of vascular function, their interrelationship and the NO-dependency of LTH. Measurements were performed twice in 27 healthy men (8 smokers), one week apart. Local application of NG-monomethyl-l-arginine (L-NMMA) by means of iontophoresis was used to determine the NO-dependency of LTH. Using L-NMMA, the peak and plateau responses of LTH were reduced by 31% (p < .001) and 65% (<0.001), respectively. For all measurements the coefficient of variation (CV) was higher in smokers than in non-smokers. For non-smokers the CV of FMD was 12%, of LTH peak response 17%, of LTH plateau response 12%, of PORH peak response 14% and of PORH area under the curve response 11%. FMD correlated weakly with the PORH peak and area under the curve response (r = 0.39 and 0.43, p < .05), whereas the LTH-plateau response correlated with the PORH peak response (r = 0.68, p < .01) in non-smokers, but FMD and LTH peak or plateau responses were unrelated. In conclusion, the LTH plateau response is for two-third NO-dependent, but unrelated to FMD. Furthermore, despite easy to perform the LTH responses are not more reproducible than FMD. Given the weak associations, the different methods of vascular function assessment are not interchangeable.
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28
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Casanova F, Adingupu DD, Adams F, Gooding KM, Looker HC, Aizawa K, Dove F, Elyas S, Belch JJF, Gates PE, Littleford RC, Gilchrist M, Colhoun HM, Shore AC, Khan F, Strain WD. The impact of cardiovascular co-morbidities and duration of diabetes on the association between microvascular function and glycaemic control. Cardiovasc Diabetol 2017; 16:114. [PMID: 28915818 PMCID: PMC5603035 DOI: 10.1186/s12933-017-0594-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 09/04/2017] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Good glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function. METHODS 743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging. RESULTS People with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p < 0.001). In regression models, cardiovascular risk factors accounted for attenuated ACh and SNP responses in CVD, whereas HbA1c accounted for the effects of T2DM. HbA1c was associated with ACh and SNP response after adjustment for cardiovascular risk factors (adjusted standardised beta (β) -0.096, p = <0.008 and -0.135, p < 0.001, respectively). Pre-existing CVD did not modify this association (β -0.099; p = 0.006 and -0.138; p < 0.001, respectively). Duration of diabetes accounted for the association between HbA1c and ACh (β -0.043; p = 0.3), but not between HbA1c and SNP (β -0.105; p = 0.02). CONCLUSIONS In those with T2DM and CVD, good glycaemic control is still associated with better microvascular function, whereas in those with prolonged disease this association is lost. This suggests duration of diabetes may be a better surrogate for "advanced disease" than concomitant CVD, although this requires prospective validation.
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Affiliation(s)
- F Casanova
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Rd, Exeter, EX2 5AX, UK
| | - D D Adingupu
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Rd, Exeter, EX2 5AX, UK
| | - F Adams
- Vascular and Inflammatory Diseases Research Unit, Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
| | - K M Gooding
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Rd, Exeter, EX2 5AX, UK
| | - H C Looker
- Vascular and Inflammatory Diseases Research Unit, Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
| | - K Aizawa
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Rd, Exeter, EX2 5AX, UK
| | - F Dove
- Vascular and Inflammatory Diseases Research Unit, Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
| | - S Elyas
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Rd, Exeter, EX2 5AX, UK
| | - J J F Belch
- Vascular and Inflammatory Diseases Research Unit, Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
| | - P E Gates
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Rd, Exeter, EX2 5AX, UK
| | - R C Littleford
- Vascular and Inflammatory Diseases Research Unit, Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
| | - M Gilchrist
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Rd, Exeter, EX2 5AX, UK
| | - H M Colhoun
- Vascular and Inflammatory Diseases Research Unit, Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
| | - A C Shore
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Rd, Exeter, EX2 5AX, UK
| | - F Khan
- Vascular and Inflammatory Diseases Research Unit, Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.
| | - W D Strain
- Diabetes and Vascular Medicine Research Centre, Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Barrack Rd, Exeter, EX2 5AX, UK.
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van der Heijden DJ, van Leeuwen MAH, Janssens GN, Lenzen MJ, van de Ven PM, Eringa EC, van Royen N. Body Mass Index Is Associated With Microvascular Endothelial Dysfunction in Patients With Treated Metabolic Risk Factors and Suspected Coronary Artery Disease. J Am Heart Assoc 2017; 6:e006082. [PMID: 28912211 PMCID: PMC5634274 DOI: 10.1161/jaha.117.006082] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Accepted: 06/21/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Obesity is key feature of the metabolic syndrome and is associated with high cardiovascular morbidity and mortality. Obesity is associated with macrovascular endothelial dysfunction, a determinant of outcome in patients with coronary artery disease. Here, we compared the influence of obesity on microvascular endothelial function to that of established cardiovascular risk factors such as diabetes mellitus, hypertension, hypercholesterolemia, and smoking in patients with suspected coronary artery disease. METHODS AND RESULTS Endothelial function was assessed during postocclusive reactive hyperemia of the brachial artery and downstream microvascular beds in 108 patients who were scheduled for coronary angiography. In all patients, microvascular vasodilation was assessed using peripheral arterial tonometry; laser Doppler flowmetry and digital thermal monitoring were performed. Body mass index was significantly associated with decreased endothelium-dependent vasodilatation measured with peripheral arterial tonometry (r=0.23, P=0.02), laser Doppler flowmetry (r=0.30, P<0.01), and digital thermal monitoring (r=0.30, P<0.01). In contrast, hypertension, hypercholesterolemia, and smoking had no influence on microvascular vasodilatation. Especially in diabetic patients, endothelial function was not significantly reduced (control versus diabetes mellitus, mean±SEM or median [interquartile range], peripheral arterial tonometry: 1.90±0.20 versus 1.67±0.20, P=0.19, laser Doppler flowmetry: 728% [interquartile range, 427-1110] versus 589% [interquartile range, 320-1067] P=0.28, and digital thermal monitoring: 6.6±1.0% versus 2.5±1.7%, P=0.08). In multivariate linear regression analysis, body mass index was the only risk factor that significantly attenuated endothelium-dependent vasodilatation using all 3 microvascular function tests. CONCLUSIONS Higher body mass index is associated with reduced endothelial function in patients with suspected coronary artery disease, even after adjustment for treated diabetes mellitus, hypertension, hypercholesterolemia, and smoking.
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Affiliation(s)
| | | | - Gladys N Janssens
- Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands
| | - Mattie J Lenzen
- Department of Cardiology, Erasmus MC Thoraxcenter, Rotterdam, the Netherlands
| | - Peter M van de Ven
- Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands
| | - Etto C Eringa
- Department of Physiology, VU University Medical Center and Institute for Cardiovascular Research, Amsterdam, the Netherlands
| | - Niels van Royen
- Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands
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30
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Lanting SM, Barwick AL, Twigg SM, Johnson NA, Baker MK, Chiu SK, Caterson ID, Chuter VH. Post-occlusive reactive hyperaemia of skin microvasculature and foot complications in type 2 diabetes. J Diabetes Complications 2017; 31:1305-1310. [PMID: 28545894 DOI: 10.1016/j.jdiacomp.2017.05.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Revised: 05/08/2017] [Accepted: 05/09/2017] [Indexed: 11/20/2022]
Abstract
AIMS Diabetes-related microvascular disease has been implicated in the development of foot ulceration and amputation. Assessment of microvascular function may be effective in identifying those at risk of diabetic foot complications. We investigated the relationship between active or previous foot complication and post-occlusive reactive hyperaemia (PORH) measured by laser-Doppler fluxmetry (LDF) in people with type 2 diabetes. METHODS PORH measures were obtained from the hallux apex in 105 people with type 2 diabetes. Associations were investigated between active or previous foot complication and PORH measures: time to peak (TtPeak) and peak as a percentage of baseline (P%BL). Multinomial logistic regression was used to determine the association of PORH with the likelihood of active foot ulcer or previous foot complication. RESULTS For each second increase in TtPeak, the likelihood of a participant having a history of foot complication is increased by 2% (OR=1.019, p=0.01). This association was not reflected in people with an active foot ulcer (OR=1.003, p=0.832). P%BL was not found to be significantly different between those with a current or previous foot complication and those without (p=0.404). CONCLUSIONS This investigation in a cohort with type 2 diabetes has demonstrated that longer TtPeak is associated with history of diabetic foot complications.
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Affiliation(s)
- Sean M Lanting
- School of Health Sciences, University of Newcastle, Australia.
| | | | - Stephen M Twigg
- Charles Perkins Centre, University of Sydney, Australia; Sydney Medical School, University of Sydney, Australia
| | - Nathan A Johnson
- Charles Perkins Centre, University of Sydney, Australia; Discipline of Exercise and Sport Science, University of Sydney, Australia
| | - Michael K Baker
- School of Exercise Science, Australian Catholic University, Australia
| | - Simon K Chiu
- School of Health Sciences, University of Newcastle, Australia
| | - Ian D Caterson
- Charles Perkins Centre, University of Sydney, Australia; Sydney Medical School, University of Sydney, Australia; School of Exercise Science, Australian Catholic University, Australia; Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Australia
| | - Vivienne H Chuter
- School of Health Sciences, University of Newcastle, Australia; Priority Research Centre for Physical activity and Nutrition, University of Newcastle
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Charwat-Resl S, Yarragudi R, Heimbach M, Leitner K, Leutner M, Gamper J, Giurgea GA, Mueller M, Koppensteiner R, Gschwandtner ME, Kautzky-Willer A, Schlager O. Microvascular function in women with former gestational diabetes: A cohort study. Diab Vasc Dis Res 2017; 14:214-220. [PMID: 28111976 DOI: 10.1177/1479164116683148] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE In the long term, diabetes mellitus is potentially associated with the occurrence of microvascular damage. This study sought to assess whether a history of prior gestational diabetes mellitus is associated with long-term effects on the women's microcirculation. METHODS Within the scope of a long-term follow-up of the 'Viennese Post-Gestational Diabetes Project', women with prior gestational diabetes mellitus as well as women with previous pregnancy but with no history of gestational diabetes mellitus (controls) were enrolled in this cross-sectional study. Microvascular function was assessed by post-occlusive reactive hyperaemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded and compared between both groups. RESULTS Microvascular function was assessed in 55 women with prior gestational diabetes mellitus (46.1 ± 4.6 years) and 32 women with previous pregnancy but without prior gestational diabetes mellitus (42.9 ± 5.3 years). The mean period of time between delivery and the assessment of microvascular function was 16.2 ± 5.2 years in women with prior gestational diabetes mellitus group and 14.2 ± 4.8 years in controls. Regarding microvascular function, baseline perfusion, biological zero, peak perfusion, time to peak and recovery time did not differ between women with prior gestational diabetes mellitus and controls (all p > 0.05). CONCLUSION In the long term, microvascular function appears not to be impaired in women with prior gestational diabetes mellitus.
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Affiliation(s)
- Silvia Charwat-Resl
- 1 Division of Angiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
- 2 Cardiology and Intensive Care Medicine, Department of Medicine II, Klinikum Wels-Grieskirchen, Wels, Austria
| | - Rajashri Yarragudi
- 3 Gender Medicine Unit, Division of Endocrinology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Moritz Heimbach
- 1 Division of Angiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
| | - Karoline Leitner
- 3 Gender Medicine Unit, Division of Endocrinology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Michael Leutner
- 3 Gender Medicine Unit, Division of Endocrinology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Jutta Gamper
- 4 Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - Georgiana-Aura Giurgea
- 1 Division of Angiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
| | - Markus Mueller
- 1 Division of Angiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
| | - Renate Koppensteiner
- 1 Division of Angiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
| | - Michael E Gschwandtner
- 1 Division of Angiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
| | - Alexandra Kautzky-Willer
- 3 Gender Medicine Unit, Division of Endocrinology, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Oliver Schlager
- 1 Division of Angiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
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Marche P, Dubois S, Abraham P, Parot-Schinkel E, Gascoin L, Humeau-Heurtier A, Ducluzeau PH, Mahe G. Neurovascular microcirculatory vasodilation mediated by C-fibers and Transient receptor potential vanilloid-type-1 channels (TRPV 1) is impaired in type 1 diabetes. Sci Rep 2017; 7:44322. [PMID: 28287157 PMCID: PMC5347083 DOI: 10.1038/srep44322] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 02/06/2017] [Indexed: 01/20/2023] Open
Abstract
Microvascular dysfunction may have an early onset in type 1 diabetes (T1D) and can precede major complications. Our objectives were to assess the endothelial-dependent (acetylcholine, ACh; and post-occlusive hyperemia, PORH), non-endothelial-dependent (sodium nitroprusside, SNP) and neurovascular-dependent (local heating, LH and current induced vasodilation, CIV) microcirculatory vasodilation in T1D patients compared with matched control subjects using a laser speckle contrast imager. Seventeen T1D patients - matched with 17 subjects according to age, gender, Body-Mass-Index, and smoking status - underwent macro- and microvascular investigations. The LH early peak assessed the transient receptor potential vanilloid type 1 channels (TRPV1) mediated vasodilation, whereas the plateau assessed the Nitirc-Oxyde (NO) and endothelium-derived hyperpolarizing factor (EDHF) pathways. PORH explored sensory nerves and (EDHF), while CIV assessed sensory nerves (C-fibers) and prostaglandin-mediated vasodilation. Using neurological investigations, we observed that C-fiber and A-delta fiber functions in T1D patients were similar to control subjects. PORH, CIV, LH peak and plateau vasodilations were significantly decreased in T1D patients compared to controls, whereas there was no difference between the two groups for ACh and SNP vasodilations. Neurovascular microcirculatory vasodilations (C-fibers and TRPV 1-mediated vasodilations) are impaired in TD1 patients whereas no abnormalities were found using clinical neurological investigations. Clinicaltrials: No. NCT02538120.
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Affiliation(s)
- P Marche
- Endocrinology Department, University Hospital of Angers, Angers, France
| | - S Dubois
- Endocrinology Department, University Hospital of Angers, Angers, France
| | - P Abraham
- Laboratory of Vascular Investigations, University Hospital of Angers, UMR CNRS6214/INSERM1083, LUNAM Université, Angers, France
| | - E Parot-Schinkel
- Methodology and Biostatistics Unit, University Hospital of Angers, Angers, France
| | - L Gascoin
- Laboratory of Vascular Investigations, University Hospital of Angers, UMR CNRS6214/INSERM1083, LUNAM Université, Angers, France
| | - A Humeau-Heurtier
- University of Angers, LARIS - Laboratoire Angevin de Recherche en Ingénierie des Systèmes, Angers, France
| | - P H Ducluzeau
- Endocrinology Department, University Hospital of Tours, Tours, France
| | - G Mahe
- INSERM Clinical Investigation Center (CIC 14 14), Rennes, France, Université de Rennes 1 and LUNAM University, Inserm 1083/CNRS 6214, Faculty of Medicine, Angers, France
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Çekiç EG, Başaran Ö, Filiz Başaran N, Elmas O, Doğan V, Mert GÖ, Mert KU, Altun I, Akın F, Biteker M. Cutaneous microvascular reactivity and aortic elasticity in coronary artery disease: Comparison of the laser Doppler flowmetry and echocardiography. Microvasc Res 2017; 109:19-25. [PMID: 27693512 DOI: 10.1016/j.mvr.2016.09.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 09/21/2016] [Accepted: 09/27/2016] [Indexed: 02/05/2023]
Affiliation(s)
- Edip Güvenç Çekiç
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Pharmacology, Turkey.
| | - Özcan Başaran
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Cardiology, Turkey
| | - Nesrin Filiz Başaran
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Pharmacology, Turkey
| | - Onur Elmas
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Physiology, Turkey
| | - Volkan Doğan
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Cardiology, Turkey
| | - Gurbet Özge Mert
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Cardiology, Turkey
| | - Kadir Uğur Mert
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Cardiology, Turkey
| | - Ibrahim Altun
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Cardiology, Turkey
| | - Fatih Akın
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Cardiology, Turkey
| | - Murat Biteker
- Mugla Sitki Kocman University, Faculty of Medicine, Department of Cardiology, Turkey
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Nakabayashi M, Ono Y. Detection of Blood Flow Speed in Shallow and Deep Tissues Using Diffuse Correlation Spectroscopy. ADVANCED BIOMEDICAL ENGINEERING 2017. [DOI: 10.14326/abe.6.53] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
| | - Yumie Ono
- Graduate School of Science and Technology, Meiji University
- Department of Electronics and Bioinformatics, School of Science and Technology, Meiji University
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Lanting SM, Johnson NA, Baker MK, Caterson ID, Chuter VH. The effect of exercise training on cutaneous microvascular reactivity: A systematic review and meta-analysis. J Sci Med Sport 2016; 20:170-177. [PMID: 27476375 DOI: 10.1016/j.jsams.2016.04.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 03/29/2016] [Accepted: 04/12/2016] [Indexed: 10/21/2022]
Abstract
OBJECTIVES This study aimed to review the efficacy of exercise training for improving cutaneous microvascular reactivity in response to local stimulus in human adults. DESIGN Systematic review with meta-analysis. METHODS A systematic search of Medline, Cinahl, AMED, Web of Science, Scopus, and Embase was conducted up to June 2015. Included studies were controlled trials assessing the effect of an exercise training intervention on cutaneous microvascular reactivity as instigated by local stimulus such as local heating, iontophoresis and post-occlusive reactive hyperaemia. Studies where the control was only measured at baseline or which included participants with vasospastic disorders were excluded. Two authors independently reviewed and selected relevant controlled trials and extracted data. Quality was assessed using the Downs and Black checklist. RESULTS Seven trials were included, with six showing a benefit of exercise training but only two reaching statistical significance with effect size ranging from -0.14 to 1.03. The meta-analysis revealed that aerobic exercise had a moderate statistically significant effect on improving cutaneous microvascular reactivity (effect size (ES)=0.43, 95% CI: 0.08-0.78, p=0.015). CONCLUSIONS Individual studies employing an exercise training intervention have tended to have small sample sizes and hence lacked sufficient power to detect clinically meaningful benefits to cutaneous microvascular reactivity. Pooled analysis revealed a clear benefit of exercise training on improving cutaneous microvascular reactivity in older and previously inactive adult cohorts. Exercise training may provide a cost-effective option for improving cutaneous microvascular reactivity in adults and may be of benefit to those with cardiovascular disease and metabolic disorders such as diabetes.
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Affiliation(s)
- Sean M Lanting
- School of Health Sciences, University of Newcastle, Australia.
| | - Nathan A Johnson
- Faculty of Health Sciences, University of Sydney, Australia; Charles Perkins Centre, University of Sydney, Australia
| | - Michael K Baker
- School of Exercise Science, Australian Catholic University, Australia
| | | | - Vivienne H Chuter
- School of Health Sciences, University of Newcastle, Australia; Priority Research Centre for Physical activity and Nutrition, University of Newcastle, Australia
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Barwick AL, Tessier JW, Janse de Jonge X, Ivers JR, Chuter VH. Peripheral sensory neuropathy is associated with altered postocclusive reactive hyperemia in the diabetic foot. BMJ Open Diabetes Res Care 2016; 4:e000235. [PMID: 27486520 PMCID: PMC4947724 DOI: 10.1136/bmjdrc-2016-000235] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 05/16/2016] [Accepted: 06/06/2016] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE This study examined whether the presence of peripheral sensory neuropathy or cardiac autonomic deficits is associated with postocclusive reactive hyperemia (reflective of microvascular function) in the diabetic foot. RESEARCH DESIGN AND METHODS 99 participants with type 2 diabetes were recruited into this cross-sectional study. The presence of peripheral sensory neuropathy was determined with standard clinical tests and cardiac autonomic function was assessed with heart rate variation testing. Postocclusive reactive hyperemia was measured with laser Doppler in the hallux. Multiple hierarchical regression was performed to examine relationships between neuropathy and the peak perfusion following occlusion and the time to reach this peak. RESULTS Peripheral sensory neuropathy predicted 22% of the variance in time to peak following occlusion (p<0.05), being associated with a slower time to peak but was not associated with the magnitude of the peak. Heart rate variation was not associated with the postocclusive reactive hyperemia response. CONCLUSIONS This study found an association between the presence of peripheral sensory neuropathy in people with diabetes and altered microvascular reactivity in the lower limb.
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Affiliation(s)
- Alex L Barwick
- Faculty of Health and Medicine , University of Newcastle , Ourimbah, New South Wales , Australia
| | - John W Tessier
- Faculty of Health and Medicine , University of Newcastle , Ourimbah, New South Wales , Australia
| | - Xanne Janse de Jonge
- Faculty of Science and Information Technology , University of Newcastle , Callaghan, New South Wales , Australia
| | - James R Ivers
- Faculty of Health and Medicine , University of Newcastle , Ourimbah, New South Wales , Australia
| | - Vivienne H Chuter
- Faculty of Health and Medicine , University of Newcastle , Ourimbah, New South Wales , Australia
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In diabetic Charcot neuroarthropathy impaired microvascular function is related to long lasting metabolic control and low grade inflammatory process. Microvasc Res 2015; 101:143-7. [DOI: 10.1016/j.mvr.2015.07.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2015] [Revised: 07/30/2015] [Accepted: 07/30/2015] [Indexed: 11/19/2022]
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Barwick A, Lanting S, Chuter V. Intra-tester and inter-tester reliability of post-occlusive reactive hyperaemia measurement at the hallux. Microvasc Res 2015; 99:67-71. [DOI: 10.1016/j.mvr.2015.03.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Revised: 03/06/2015] [Accepted: 03/07/2015] [Indexed: 11/29/2022]
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Adingupu DD, Thorn CE, Casanova F, Elyas S, Gooding K, Gilchrist M, Aizawa K, Gates PE, Shore AC, Strain DW. Blood Oxygen Saturation After Ischemia is Altered With Abnormal Microvascular Reperfusion. Microcirculation 2015; 22:294-305. [DOI: 10.1111/micc.12198] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Accepted: 02/28/2015] [Indexed: 11/30/2022]
Affiliation(s)
- Damilola D. Adingupu
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
| | - Clare E. Thorn
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
| | - Francesco Casanova
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
| | - Salim Elyas
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
| | - Kim Gooding
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
| | - Mark Gilchrist
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
| | - Kunihiko Aizawa
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
| | - Phillip E. Gates
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
| | - Angela C. Shore
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
| | - David W. Strain
- Vascular Medicine; Institute of Biomedical and Clinical Science and NIHR Exeter Clinical Research Facility; University of Exeter Medical School; Exeter UK
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Effect of bariatric surgery on microvascular dysfunction associated to metabolic syndrome: a 12-month prospective study. Int J Obes (Lond) 2014; 38:1410-5. [PMID: 24468701 DOI: 10.1038/ijo.2014.15] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2013] [Revised: 12/17/2013] [Accepted: 01/17/2014] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To prospectively evaluate the effect of weight loss after bariatric surgery on microvascular function in morbidly obese patients with and without metabolic syndrome (MetS). METHODS A cohort of morbidly obese patients with and without MetS was studied before surgery and after 12 months of surgery. Healthy lean controls were also examined. Microvascular function was assessed by postocclusive reactive hyperemia (PORH) at forearm skin evaluated by laser Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated from laser-Doppler skin blood flow and blood pressure. Regression analysis was performed to assess the contribution of different clinical, metabolic and biochemical parameters to microvascular function. RESULTS Before surgery, 62 obese patients, 39 with MetS and 23 without MetS, and 30 lean control subjects were analyzed. The absolute area under the hyperemic curve (AUC(H)) CVC of PORH was significantly decreased in obese patients compared with lean control subjects. One year after surgery, AUC(H) CVC significantly increased in patients free of MetS, including patients that had MetS before surgery. In contrast, AUC(H) CVC did not significantly change in patients in whom MetS persisted after surgery. Stepwise multivariate regression analysis showed that only changes in HDL cholesterol (HDL-C) and oxidized LDL (oxLDL) independently predicted improvement of AUC(H) after surgery. These two variables together accounted for 40.9% of the variability of change in AUC(H) CVC after surgery. CONCLUSIONS Bariatric surgery could significantly improve microvascular dysfunction in obese patients, but only in patients free of MetS after surgery. Improvement of microvascular dysfunction is strictly associated to postoperative increase in HDL-C levels and decrease in oxLDL levels.
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Wojtkiewicz S, Wojcik-Sosnowska E, Jasik M, Maniewski R, Karnafel W, Liebert A. Assessment of speed distribution of red blood cells in the microvascular network in healthy volunteers and type 1 diabetes using laser Doppler spectra decomposition. Physiol Meas 2014; 35:283-95. [PMID: 24434915 DOI: 10.1088/0967-3334/35/2/283] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
We applied a recently reported method of decomposition of laser Doppler power density spectra for in vivo monitoring of speed distributions of red blood cells (RBCs) in the microvascular network. The spectrum decomposition technique allows us to derive the distribution of RBC speed (in absolute units (mm s(-1))) versus RBC concentration (in arbitrary units). We carried out postocclusive reactive hyperaemia (PORH) test in 15 healthy volunteers and 21 diabetic patients in which the duration of type 1 diabetes was longer than 10 years. Measurements were carried out simultaneously with the use of a typical laser Doppler commercial instrument and speed resolved laser Doppler instrument utilizing the new technique based on decomposition of the laser Doppler spectra. We show that for the classical laser Doppler instrument, none of the PORH parameters revealed a statistical significance of difference between the groups analyzed. In contrast, the RBC speed distributions obtained from laser Doppler spectra during rest in the control group and type 1 diabetes are statistically significant. This result suggests that speed distribution measurements in the rest state (without any kind of stimulation test) allows for the assessment of microcirculation disorders. Measurements carried out in healthy subjects show that the first moment of speed distributions (mean speed of the distributions) is 2.32 ± 0.54 mm s(-1) and 2.57 ± 0.41 mm s(-1) for optodes located on the toe and finger of the hand, respectively. Respective values in type 1 diabetes were higher: 3.00 ± 0.36 mm s(-1) and 3.10 ± 0.48 mm s(-1).
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Affiliation(s)
- S Wojtkiewicz
- Nalecz Institute of Biocybernetics and Biomedical Engineering, Warsaw, Poland
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Gargiulo S, Gramanzini M, Liuzzi R, Greco A, Brunetti A, Vesce G. Effects of some anesthetic agents on skin microcirculation evaluated by laser Doppler perfusion imaging in mice. BMC Vet Res 2013; 9:255. [PMID: 24341447 PMCID: PMC3878498 DOI: 10.1186/1746-6148-9-255] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Accepted: 12/02/2013] [Indexed: 11/30/2022] Open
Abstract
Background Anesthetic agents alter microcirculation, influencing tissue oxygenation and delivery of vital substrates. Laser Doppler perfusion imaging is a widespread technique in the field of microvascular research that can evaluate noninvasively and in real time the effects of environmental conditions, physical manipulations, diseases and treatments on peripheral perfusion. This study aims to evaluate laser Doppler perfusion imaging as a means to detect changes in skin microcirculation induced by some popular anesthetic agents in a murine model. Twenty-four age- and gender-matched healthy CD1 mice were examined by laser Doppler perfusion imaging. The skin microcirculatory response was measured at the level of plantar surfaces during isoflurane anesthesia with or without subsequent dexmedetomidine or acepromazine. At the end of the procedure, dexmedetomidine was reversed by atipamezole administration. Results In all mice, skin blood flow under isoflurane anesthesia did not show significant differences over time (P = 0.1). The serial perfusion pattern and values following acepromazine or dexmedetomidine administration differed significantly (P < 0.05). Conclusions We standardized a reliable laser Doppler perfusion imaging protocol to non-invasively assess changes in skin microcirculation induced by anesthesia in mice, considering the advantages and drawbacks of this technique and its translational value.
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Affiliation(s)
- Sara Gargiulo
- Institute of Biostructures and Bioimages of the National Council of Research, Via T, De Amicis 95, Naples 80145, Italy.
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Tomešová J, Gruberova J, Lacigova S, Cechurova D, Jankovec Z, Rusavy Z. Differences in skin microcirculation on the upper and lower extremities in patients with diabetes mellitus: relationship of diabetic neuropathy and skin microcirculation. Diabetes Technol Ther 2013; 15:968-75. [PMID: 23964895 DOI: 10.1089/dia.2013.0083] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION During recent years, the role of microcirculation has received increasing attention especially for its potential pathogenic role in the development of diabetes complications, particularly diabetic foot syndrome. The aim of this study was to evaluate the differences in the skin microcirculatory reactivity on the upper and lower extremities (UE and LE, respectively) in the patient with type 2 diabetes mellitus (T2DM). We also evaluated the changes in the skin microcirculation independently of the individual test for peripheral diabetic neuropathy (DN) diagnosis (Semmes-Weinstein monofilaments, Bio-Thesiometer [Bio-Medical Instrument Co., Newbury, OH], and Neuropad(®) [TRIGOcare International GmbH, Wiehl, Germany]). PATIENTS AND METHODS Fifty-two patients with T2DM were enrolled. Microvascular reactivity was measured by laser Doppler iontophoresis, using 1% acetylcholine chloride (ACH) and 1% sodium nitroprusside. RESULTS Significant reduction of perfusion was found in LE compared with UE when using ACH. In patients with DN skin microvascular reactivity on LE and UE was reduced, compared with patients without DN. Impaired skin microvascular reactivity to ACH (dominant on LE) was demonstrated in all patients who were positive in at least one of the tests for the presence of DN. CONCLUSIONS Reactivity of the skin microcirculation is worse on the foot than on the hand. This study confirmed a close relationship of DN and impaired skin microcirculation. It seems that autonomous neuropathy (assessed using the Neuropad) precedes the manifestation of somatosensory neuropathy.
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Affiliation(s)
- Jitka Tomešová
- The Faculty of Medicine in Pilsen, Charles University in Prague , Pilsen, Czech Republic
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Babos L, Járai Z, Nemcsik J. Evaluation of microvascular reactivity with laser Doppler flowmetry in chronic kidney disease. World J Nephrol 2013; 2:77-83. [PMID: 24255889 PMCID: PMC3832914 DOI: 10.5527/wjn.v2.i3.77] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Revised: 07/31/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular diseases are the major causes of mortality in patients with chronic kidney disease (CKD). The complex process of accelerated athero- and arteriosclerosis in CKD is associated with this phenomenon, where endothelial dysfunction (ED) is one of the initial steps. Hence, the early diagnosis of ED can potentially lead to early interventions which could result in a better outcome for these patients. Several methodologies have been developed for the diagnosis of ED. Laser Doppler flowmetry (LDF) enables us to study the microcirculation continuously in a non-invasive manner. In our review we would like to focus on different tests developed for LDF, like postocclusive reactive hyperaemia, local heating, iontophoresis, microdialysis or analysis of flowmotion. We would also like to summarize the available data in CKD with these methodologies to enlighten their perspectives in the clinical use on this patient population.
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Roustit M, Cracowski JL. Assessment of endothelial and neurovascular function in human skin microcirculation. Trends Pharmacol Sci 2013; 34:373-84. [DOI: 10.1016/j.tips.2013.05.007] [Citation(s) in RCA: 177] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Revised: 05/03/2013] [Accepted: 05/17/2013] [Indexed: 10/26/2022]
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Schlager O, Widhalm K, Hammer A, Giurgea A, Margeta C, Fritsch M, Zehetmayer S, Koppensteiner R, Gschwandtner ME, Willfort-Ehringer A. Familial hypercholesterolemia affects microvascular autoregulation in children. Metabolism 2013; 62:820-7. [PMID: 23357531 DOI: 10.1016/j.metabol.2012.12.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2012] [Revised: 12/03/2012] [Accepted: 12/22/2012] [Indexed: 10/27/2022]
Abstract
OBJECTIVE Familial hypercholesterolemia (FH) impairs macrovascular endothelial function in childhood and causes an increase of cardiovascular risk in later life. Whether microvascular function is affected in children with FH is unknown. The aim of this study was to investigate the impact of FH on microvascular autoregulation in children by post occlusive reactive hyperemia (PORH). METHODS PORH of the skin was assessed using laser Doppler fluxmetry. Baseline perfusion, biological zero, defined as no-flow laser Doppler signal during suprasystolic occlusion, peak perfusion after release of suprasystolic occlusion, as well as time to peak perfusion and recovery time, defined as time until baseline perfusion is resumed, were measured in 16 children, who were diagnosed with FH according to current guidelines, and in 91 healthy controls. RESULTS In children with FH, peak perfusion was higher (FH: 1.60±0.68 vs. controls: 1.26±0.50 AU [arbitrary units], p=0.02), recovery time was longer (110±42.61 vs. 83.18±35.08 s, p=0.01) and biological zero was lower than in controls (0.12±0.04 vs. 0.18±0.05 AU, p<0.001). Baseline perfusion and time to peak were not different between children with FH and controls (baseline perfusion: 0.43±0.21 vs. 0.38±0.15 AU, p=0.18; time to peak: 15.44±12.25 vs. 18.18±17.79 s, p=0.56). CONCLUSION For the first time the present study reveals an impact of FH on microvascular autoregulation in children: the differences of PORH between children with FH and controls indicate an affected autoregulation of microvascular blood flow in FH, which has its onset in childhood.
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Affiliation(s)
- Oliver Schlager
- Department of Medicine II, Division of Angiology, Medical University of Vienna, Austria
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Khan F, Choong WL, Du Q, Jovanović A. Real-time RT-PCR threshold cycles value for Kir6.1 from the blood correlates with parameters of vascular function: a potential for the vascular function biomarker? Biomarkers 2013; 18:221-9. [PMID: 23480296 DOI: 10.3109/1354750x.2013.770553] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Abstract We examined the presence of KATP channel subunits, Kir6.1 and SUR2B, mRNAs in the blood and vascular function in healthy volunteers (41 males, 34 females). Real-time reverse transcriptase (RT)-PCR threshold cycles (Ct) was used as an indicator of mRNA levels. Baseline skin perfusion and the post-occlusion reactive hyperemia response exhibited a significant positive correlation with Ct for Kir6.1. There was no correlation between Kir6.1 Ct and brachial artery flow-mediated dilatation. Gender had no influence on relationships between blood Kir6.1 Ct and vascular function. We conclude that blood Kir6.1 mRNA levels could be potentially used as a biomarker of the vascular function.
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Affiliation(s)
- Faisel Khan
- Medical Research Institute, Division of Cardiovascular and Diabetic Medicine, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK
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Humeau-Heurtier A, Mahé G, Durand S, Henrion D, Abraham P. Laser speckle contrast imaging: Multifractal analysis of data recorded in healthy subjects. Med Phys 2012; 39:5849-56. [DOI: 10.1118/1.4748506] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
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Schlager O, Hammer A, Willfort-Ehringer A, Fritsch M, Rami-Merhar B, Schober E, Nagl K, Giurgea A, Margeta C, Zehetmayer S, Schernthaner GH, Koppensteiner R, Gschwandtner ME. Microvascular autoregulation in children and adolescents with type 1 diabetes mellitus. Diabetologia 2012; 55:1633-40. [PMID: 22366881 DOI: 10.1007/s00125-012-2502-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Accepted: 01/16/2012] [Indexed: 12/31/2022]
Abstract
AIMS/HYPOTHESIS Deterioration of microvascular function may have an early onset in individuals with type 1 diabetes mellitus. We hypothesised that microvascular autoregulation is impaired in children with type 1 diabetes and can be detected non-invasively by postocclusive reactive hyperaemia (PORH). METHODS Microvascular autoregulation was assessed in 58 children with type 1 diabetes and 58 age- and sex-matched healthy controls by PORH using laser Doppler fluxmetry. Baseline perfusion, biological zero (defined as a 'no flow' laser Doppler signal during suprasystolic occlusion), peak perfusion following occlusion, time to peak and recovery time (time until baseline perfusion is resumed) were recorded and compared between the groups. RESULTS Peak perfusion was higher in children with type 1 diabetes than in healthy controls (1.7 ± 0.93 AU [arbitrary units] vs 1.29 ± 0.46 AU; p = 0.004), and biological zero was lower in children with type 1 diabetes vs controls (0.14 ± 0.04 AU vs 0.19 ± 0.04 AU; p < 0.0001). No differences were seen between the groups in baseline perfusion, time to peak during PORH and recovery time following PORH. CONCLUSIONS/INTERPRETATION PORH reveals impaired microvascular autoregulation in children with type 1 diabetes. The higher peak perfusion might reflect a decline in the vasoconstrictive ability of arteriolar smooth muscle cells upstream of capillary beds in children with type 1 diabetes.
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Affiliation(s)
- O Schlager
- Department of Medicine II, Division of Angiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
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Montero D, Walther G, Perez-Martin A, Roche E, Vinet A. Endothelial dysfunction, inflammation, and oxidative stress in obese children and adolescents: markers and effect of lifestyle intervention. Obes Rev 2012; 13:441-55. [PMID: 22133012 DOI: 10.1111/j.1467-789x.2011.00956.x] [Citation(s) in RCA: 110] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
With an increasing prevalence, pediatric obesity is often a prelude to adulthood obesity, and represents a major public health issue. Comorbidities are very common and severe in obese adults, justifying the search for earlier markers or risk factors for cardiovascular diseases in obese children. Endothelial dysfunction has been found to be present in the early stages of atherosclerosis, and can be non-invasively assessed with widely accepted and well-standardized techniques at the macrocirculation level. Endothelial dysfunction at the microcirculation level is less documented in obese children. Obesity in children has been repeatedly and independently correlated to endothelial dysfunction, inflammation and oxidative stress markers, although the relationship between these factors remains to be investigated. However, this would not only allow substantial improvements in risk stratification, but also provide essential data regarding the evolution of endothelial dysfunction in childhood obesity, especially during puberty when pro-inflammatory and pro-oxidative changes, with relative insulin resistance, occur. Therapeutic strategies such as lifestyle interventions in early childhood obesity appear all the more necessary, optimally including both exercise and diet because of their known effects on inflammatory and oxidative stress markers, potentially reversing endothelial dysfunction.
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Affiliation(s)
- D Montero
- Pharm-Ecology Cardiovascular Laboratory, Faculty of Sciences, Avignon, France
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