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Kotan R, Peto K, Deak A, Szentkereszty Z, Nemeth N. Hemorheological and Microcirculatory Relations of Acute Pancreatitis. Metabolites 2022; 13:metabo13010004. [PMID: 36676930 PMCID: PMC9863893 DOI: 10.3390/metabo13010004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 12/04/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Acute pancreatitis still means a serious challenge in clinical practice. Its pathomechanism is complex and has yet to be fully elucidated. Rheological properties of blood play an important role in tissue perfusion and show non-specific changes in acute pancreatitis. An increase in blood and plasma viscosity, impairment of red blood cell deformability, and enhanced red blood cell aggregation caused by metabolic, inflammatory, free radical-related changes and mechanical stress contribute to the deterioration of the blood flow in the large vessels and also in the microcirculation. Revealing the significance of these changes in acute pancreatitis may better explain the pathogenesis and optimize the therapy. In this review, we give an overview of the role of impaired microcirculation by changes in hemorheological properties in acute pancreatitis.
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Affiliation(s)
- Robert Kotan
- Endocrine Surgery Unit, Linköping University Hospital, Universitetssjukhuset, 581 85 Linköping, Sweden
| | - Katalin Peto
- Department of Operative Techniques and Surgical Research, Faculty of Medicine, University of Debrecen, Moricz Zsigmond ut 22, H-4032 Debrecen, Hungary
| | - Adam Deak
- Department of Operative Techniques and Surgical Research, Faculty of Medicine, University of Debrecen, Moricz Zsigmond ut 22, H-4032 Debrecen, Hungary
| | - Zsolt Szentkereszty
- Department of Surgery, Faculty of Medicine, University of Debrecen, Moricz Zsigmond ut 22, H-4032 Debrecen, Hungary
| | - Norbert Nemeth
- Department of Operative Techniques and Surgical Research, Faculty of Medicine, University of Debrecen, Moricz Zsigmond ut 22, H-4032 Debrecen, Hungary
- Correspondence: ; Tel./Fax: +36-52-416-915
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Abstract
It has been 30 years since the first member of the protease-activated receptor (PAR) family was discovered. This was followed by the discovery of three other receptors, including PAR2. PAR2 is a G protein-coupled receptor activated by trypsin site-specific proteolysis. The process starts with serine proteases acting between arginine and serine, creating an N-terminus that functions as a tethered ligand that binds, after a conformational change, to the second extracellular loop of the receptor, leading to activation of G-proteins. The physiological and pathological functions of this ubiquitous receptor are still elusive. This review focuses on PAR2 activation and its distribution under physiological and pathological conditions, with a particular focus on the pancreas, a significant producer of trypsin, which is the prototype activator of the receptor. The role in acute or chronic pancreatitis, pancreatic cancer, and diabetes mellitus will be highlighted.
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Affiliation(s)
- Petr SUHAJ
- Department of Pathology and Molecular Medicine, Thomayer University Hospital, Prague, Czech Republic,Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Tomas OLEJAR
- Department of Pathology and Molecular Medicine, Thomayer University Hospital, Prague, Czech Republic,Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Radoslav MATEJ
- Department of Pathology and Molecular Medicine, Thomayer University Hospital, Prague, Czech Republic,Department of Pathology, University Hospital Kralovske Vinohrady, Prague, Czech Republic,Third Faculty of Medicine, Charles University, Prague, Czech Republic
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Simons-Linares CR, Imam Z, Chahal P. Viral-Attributed Acute Pancreatitis: A Systematic Review. Dig Dis Sci 2021; 66:2162-2172. [PMID: 32789532 DOI: 10.1007/s10620-020-06531-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 07/31/2020] [Indexed: 01/18/2023]
Abstract
Infectious etiologies are rare cause of acute pancreatitis (AP). We sought to investigate the frequency of viral-attributed AP (VIAP) and describe its natural course and clinical features. Comprehensive review of PubMed and EMBASE in English until December 31, 2019, was performed. AP diagnosis and severity were defined per the Revised Atlanta Classification. Viral infections were diagnosed by serology and/or histology. A diagnosis of viral infection, with a concurrent AP diagnosis, a temporal resolution of both entities, and the attempt to exclude the most common etiologies of AP defined VIAP. Two independent reviewers reviewed eligible publications. Bias risk was assessed with the Murad tool. A total of 209 cases identified in 128 publications met inclusion criteria. Mean age was 38.9 ± 1.28 years. Male-to-female ratio was 2.2:1, and 28% of patients were immunocompromised. Viral hepatitis (A, B, C, D and E) was the most common virus and accounted for 34.4% of cases, followed by coxsackie and echoviruses (14.8%), hemorrhagic fever viruses (12.4%), CMV (12.0%), VZV (10.5%), mumps and measles (3.8%), primary HIV infection (3.8%), HSV (1.9%), EBV (1.9%), and the remainder of cases (2.9%) attributed to adenovirus, influenza H1N1, and multiple viruses. Severity of AP was: 43.1% mild, 11.7% moderately severe, 32.4% severe. Death occurred in 42 (20.1%) patients. A significant portion of VIAP patients were immunocompromised (28.0%) and accounted for 71.4% of mortality cases. Mortality was higher than that reported for AP from other etiologies in the literature.
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Affiliation(s)
- C Roberto Simons-Linares
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
| | - Zaid Imam
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA
| | - Prabhleen Chahal
- Gastroenterology and Hepatology Department, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
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Imam Z, Simons-Linares CR, Chahal P. Infectious causes of acute pancreatitis: A systematic review. Pancreatology 2020; 20:1312-1322. [PMID: 32938554 DOI: 10.1016/j.pan.2020.08.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 08/21/2020] [Accepted: 08/24/2020] [Indexed: 01/18/2023]
Abstract
BACKGROUND Infectious etiologies of acute pancreatitis (AP) are rare and include viruses, bacteria, mycobacteria, parasites, and fungi. We aimed to conduct a comprehensive review on infectious etiologies of AP analyzing the frequency, clinical features, and outcomes of individuals presenting with this condition. METHODS Eligible articles reporting on AP attributed to infectious etiologies were included. A comprehensive literature search of PubMed from time of inception and until September 6,2019 was performed using all relevant MeSH (medical subject heading) keywords. Articles were assessed for eligibility and independently reviewed by two reviewers for clinical features of AP, local complications, and mortality. Methodological quality of included studies was evaluated using the Murad tool. RESULTS A total of 212 articles were included, of which 168 (79.2%) were at high risk of bias. 320 cases of AP were identified. Viruses were the leading etiology of infection attributed AP (65.3%) followed by helminths (19.1%), and bacteria (12.5%). Protozoa, mycobacteria, and fungi accounted for the remaining 3.1% of cases. Mean age was 40.5 ± 18.4 years and M:F ratio was 1.94:1. Mortality occurred in 50 patients. Mortality rate was higher in the virus attributed AP patients than AP from other infectious etiologies (21.8% vs. 7.0%, p < 0.0005). INTERPRETATION Literature quality on infection attributed AP is limited. Virus attributed AP appears to carry a higher mortality than other etiologies of infection attributed AP.
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Affiliation(s)
- Zaid Imam
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA
| | - C Roberto Simons-Linares
- Department of Gastroenterology, Hepatology, and Nutrition; Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
| | - Prabhleen Chahal
- Department of Gastroenterology, Hepatology, and Nutrition; Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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Jansson L, Carlsson PO. Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans. Compr Physiol 2019; 9:799-837. [PMID: 30892693 DOI: 10.1002/cphy.c160050] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The pancreatic islets are more richly vascularized than the exocrine pancreas, and possess a 5- to 10-fold higher basal and stimulated blood flow, which is separately regulated. This is reflected in the vascular anatomy of the pancreas where islets have separate arterioles. There is also an insulo-acinar portal system, where numerous venules connect each islet to the acinar capillaries. Both islets and acini possess strong metabolic regulation of their blood perfusion. Of particular importance, especially in the islets, is adenosine and ATP/ADP. Basal and stimulated blood flow is modified by local endothelial mediators, the nervous system as well as gastrointestinal hormones. Normally the responses to the nervous system, especially the parasympathetic and sympathetic nerves, are fairly similar in endocrine and exocrine parts. The islets seem to be more sensitive to the effects of endothelial mediators, especially nitric oxide, which is a permissive factor to maintain the high basal islet blood flow. The gastrointestinal hormones with pancreatic effects mainly influence the exocrine pancreatic blood flow, whereas islets are less affected. A notable exception is incretin hormones and adipokines, which preferentially affect islet vasculature. Islet hormones can influence both exocrine and endocrine blood vessels, and these complex effects are discussed. Secondary changes in pancreatic and islet blood flow occur during several conditions. To what extent changes in blood perfusion may affect the pathogenesis of pancreatic diseases is discussed. Both type 2 diabetes mellitus and acute pancreatitis are conditions where we think there is evidence that blood flow may contribute to disease manifestations. © 2019 American Physiological Society. Compr Physiol 9:799-837, 2019.
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Affiliation(s)
- Leif Jansson
- Uppsala University, Department of Medical Cell Biology, Uppsala, Sweden
| | - Per-Ola Carlsson
- Uppsala University, Department of Medical Cell Biology, Uppsala, Sweden.,Uppsala University, Department of Medical Sciences, Uppsala, Sweden
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Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:5264592. [PMID: 29686719 PMCID: PMC5857302 DOI: 10.1155/2018/5264592] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 11/29/2017] [Accepted: 12/20/2017] [Indexed: 12/11/2022]
Abstract
Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis.
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Chrysikos DT, Sergentanis TN, Zagouri F, Psaltopoulou T, Flessas I, Agrogiannis G, Alexakis N, Bramis I, Patsouri EE, Patsouris ES, Korontzi M, Katsarou A, Zografos GC, Papalois AE. The effect of U-74389G on pancreas ischemia–reperfusion injury in a swine model. J Surg Res 2014; 187:450-7. [DOI: 10.1016/j.jss.2013.11.1082] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Revised: 10/22/2013] [Accepted: 11/11/2013] [Indexed: 12/18/2022]
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Löhr JM, Haas S. Can a polymorphism in the thalassemia gene and a heterozygote CFTR mutation cause acute pancreatitis? World J Clin Cases 2014; 2:62-66. [PMID: 24653987 PMCID: PMC3955802 DOI: 10.12998/wjcc.v2.i3.62] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 12/10/2013] [Accepted: 01/15/2014] [Indexed: 02/05/2023] Open
Abstract
The case of a 32-year-old black woman of African descent who suffered from repeated episodes of acute pancreatitis, initially triggered when flying on airplanes, is reported. She did not drink alcohol or smoke. Genetic analysis was negative for cationic trypsinogen, serine protease inhibitor Kazal type 1 and chymotrypsin C. However, hemoglobin F was elevated. Sequencing of the thalassemia gene revealed a novel alteration in the 5' region indicative of a functional abnormality of the molecule. Sequencing the cystic fibrosis transmembrane conductance regulator (CFTR) gene revealed a heterozygote sequence variant. The combination of a hemoglobin gene mutation known for thalassemia in conjunction with the hitherto undescribed CFTR mutation is suggested to pave the road for initial and repetitive pancreatitis attacks. This will be discussed.
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Apostolidis D, Ntinas A, Kardassis D, Koulouris N, Thomareis O, Karayannopoulou G, Vrochides D. Nimesulide may be more efficient than allopurinol in protecting pancreas from acute ischemia/reperfusion injury in an animal model. Vasc Endovascular Surg 2012; 46:654-63. [PMID: 23129584 DOI: 10.1177/1538574412465478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To determine the influence of allopurinol and nimesulide in the protection of the pancreas from acute ischemia-reperfusion (I/R) injury. MATERIALS AND METHODS A total of 30 rabbits were divided into 3 groups, group A: acute I/R only; group B: allopurinol (30 mg/kg) was administered intravenously 10 minutes before ischemia; group C: nimesulide (50 mg/kg) was given intraperitoneally 20 minutes before ischemia. Neopterin and superoxide dismutase (SOD) levels were examined. Pancreatic biopsies were obtained for electron microscopy study. RESULTS The mean neopterin concentrations in group A are 3.56 ± 3.41, 7.74 ± 3.59, and 8.94 ± 2.86 ng/mL, respectively, in the stabilization, ischemia, and reperfusion phases; group B: 3.40 ± 3.03, 7.45 ± 8.89, and 10.64 ± 7.47 ng/mL; and group C: 3.41 ± 2.71, 5.67 ± 2.76, and 4.34 ± 2.87 ng/mL. The mean SOD concentrations in group A are 4.25 ± 1.79, 4.48 ± 1.60, and 5.57 ± 1.15 ng/mL; group B: 4.32 ± 0.81, 5.08 ± 1.10, and 4.45 ± 1.31 ng/mL; and group C: 4.10 ± 0.99, 5.23 ± 1.60, and 3.72 ± 1.30 ng/mL. Histopathology showed the least deterioration in group C. CONCLUSION Nimesulide is more efficient than allopurinol in protecting pancreas from acute I/R injury.
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Curcumin attenuates airway hyperreactivity induced by ischemia-reperfusion of the pancreas in rats. Transplant Proc 2010; 42:744-7. [PMID: 20430162 DOI: 10.1016/j.transproceed.2010.03.017] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Ischemia-reperfusion (I/R) of the rat pancreas induces acute pancreatitis with a systemic inflammatory response. Activated inflammatory cells are sequestered in the lung, and the consequent respiratory burst may increase airway reactivity. In this study, we characterized the effect of the antioxidant curcumin on airway hyperreactivity induced by pancreatic I/R. METHODS Ischemia of the pancreas was induced by clamping the gastroduodenal and the splenic artery for 2 hours followed by reperfusion for 6 hours. The pulmonary function data of Penh, a measurement of airway resistance, were used to show the airway responses to a methacholine challenge. The blood concentration of oxygen radicals, nitric oxide, and tumor necrosis factor-alpha (TNFalpha) were measured after pancreatic I/R. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFalpha in lung tissues were measured after pancreatic I/R. Pretreatment with curcumin (20 mg/kg) was administered by intraperitoneal injection 2 hours before pancreatic I/R. RESULTS The protocol resulted in significant elevations of the blood concentrations of amylase, hydroxyl radical, nitric oxide, TNFalpha, and white cells among the I/R group. iNOS and TNFalpha mRNA expressions also significantly increased in lung tissues. Pulmonary function data showed that pancreatic I/R induced significant increases in responses to methacholine challenge: Penh increased significantly in the I/R group when compared with the sham group. Pretreatment with curcumin significantly attenuated the inflammatory, oxidative, and nitrosative responses and lung tissue iNOS and TNFalpha expressions. Curcumin also attenuated airway reactivity to methacholine challenge. CONCLUSIONS I/R of the pancreas induced systemic inflammatory responses with respiratory burst, nitrosative stress, and hyperresponses in the airways. Curcumin, which has antioxidant and anti-inflammatory effects, significantly attenuated the inflammatory responses and airway hyperreactivity induced by pancreatic I/R.
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Chen P, Hu B, Tan Q, Liu L, Li D, Jiang C, Wu H, Li J, Tang C. Role of neurocrine somatostatin on sphincter of Oddi contractility and intestinal ischemia reperfusion-induced acute pancreatitis in macaques. Neurogastroenterol Motil 2010; 22:935-e240. [PMID: 20497509 DOI: 10.1111/j.1365-2982.2010.01506.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Intestinal ischemia-reperfusion (IIR) is implicated in the pathogenesis of severe acute pancreatitis (SAP). This study investigates the impact of neurocrine somatostatin (SST) on the contraction of sphincter of Oddi (SO) during IIR. METHODS Intestinal ischemia-reperfusion model in macaques was induced by occluding the superior mesenteric artery. Pancreatitis was confirmed by pancreatic histology and serum levels of amylase and lipase. SST and its receptors (SSTRs) in SO were visualized by immunohistochemistry. Effects of SST on the contraction of the isolated SO were recorded in vitro. KEY RESULTS Inflammatory scores of the pancreas and serum levels of amylase or lipase in the macaques that underwent IIR were significantly higher than those in the control group. The frequency and amplitude of phasic contraction of the circular muscle in SO was increased by SST in a concentration-dependent manner. Compared with the control group, SST innervation or SSTR2 expression in SO of macaques treated with IIR was increased 5.2 fold or 5.6 fold respectively. Prophylactic infusion of SST before IIR significantly reduced SST immunoreactive fibers in SO as compared to those in the IIR group and remarkably alleviated the pathophysiologic changes due to IIR. CONCLUSIONS & INFERENCES Increased SST innervation in SO during the early phase of IIR associated with the contraction of circular muscle of SO, which might be one of the promoting factors associated with the development of SAP. Prevention of IIR or intervention of SO contraction after occurrence of acute pancreatitis might be beneficial for preventing SAP.
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Affiliation(s)
- P Chen
- Department of Gastroenterology, West China Hospital, Chengdu, China
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Abstract
Reactive oxygen and reactive nitrogen species (ROS/RNS) have been implicated in the pathogenesis of acute and chronic pancreatitis. Clinical and basic science studies have indicated that ROS/RNS formation processes are intimately linked to the development of the inflammatory disorders. The detrimental effects of highly reactive ROS/RNS are mediated by their direct actions on biomolecules (lipids, proteins, and nucleic acids) and activation of proinflammatory signal cascades, which subsequently lead to activation of immune responses. The present article summarizes the possible sources of ROS/RNS formation and the detailed signaling cascades implicated in the pathogenesis of pancreatic inflammation, as observed in acute and chronic pancreatitis. A therapeutic ROS/RNS-scavenging strategy has been advocated for decades; however, clinical studies examining such approaches have been inconsistent in their results. Emerging evidence indicates that pancreatitis-inducing ROS/RNS generation may be attenuated by targeting ROS/RNS-generating enzymes and upstream mediators.
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Affiliation(s)
- Po Sing Leung
- Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
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Lo HA, Sun LN, Chen CF, Wang D, Zhang HP. Ischemia-Reperfusion of the Pancreas Induced Hyperresponsiveness of the Airways in Rats. Transplant Proc 2009; 41:63-6. [DOI: 10.1016/j.transproceed.2008.08.156] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2008] [Accepted: 08/06/2008] [Indexed: 12/12/2022]
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Gardner TB, Vege SS, Pearson RK, Chari ST. Fluid resuscitation in acute pancreatitis. Clin Gastroenterol Hepatol 2008; 6:1070-6. [PMID: 18619920 DOI: 10.1016/j.cgh.2008.05.005] [Citation(s) in RCA: 109] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2008] [Accepted: 05/04/2008] [Indexed: 02/07/2023]
Abstract
Acute pancreatitis is a common inflammatory disorder of the pancreas resulting in considerable morbidity and a mortality rate of approximately 5%. Although there are no pharmacologic treatments known to improve important outcomes, aggressive intravenous fluid resuscitation generally is recommended in all patients. However, few human investigations have been performed and several important questions have not been answered. For example, what is the optimal resuscitative fluid? Is there a role for colloid solutions? To what clinical marker should resuscitation be targeted? When is the best time to start such fluids and in which group of patients? This review describes the microcirculation of the pancreas and the pathophysiologic alterations caused by acute pancreatitis. Previous animal experiments are described, as are the limited human studies specifically addressing fluid resuscitation. Finally, current recommendations and goals for further investigation are highlighted. It is our hope that this review will stimulate interest in this often overlooked subject and lead to carefully designed human clinical trials using varying fluid solutions and rates, with an emphasis on patient monitoring and safety, in the near future.
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Affiliation(s)
- Timothy B Gardner
- Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA
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Chen C, Chen H, Wang D, Li J, Fong Y. Restrictive Ventilatory Insufficiency and Lung Injury Induced by Ischemia/Reperfusion of the Pancreas in Rats. Transplant Proc 2008; 40:2185-7. [DOI: 10.1016/j.transproceed.2008.07.093] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Comert B, Isik AT, Aydin S, Bozoglu E, Unal B, Deveci S, Mas N, Cinar E, Mas MR. Combination of allopurinol and hyperbaric oxygen therapy: a new treatment in experimental acute necrotizing pancreatitis? World J Gastroenterol 2007; 13:6203-6207. [PMID: 18069760 PMCID: PMC4171230 DOI: 10.3748/wjg.v13.i46.6203] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2007] [Revised: 09/16/2007] [Accepted: 10/28/2007] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the individual and combined effects of allopurinol and hyperbaric oxygen (HBO) therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation (BT) in the experimental rat acute pancreatitis (AP). METHODS Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls (sham, Group I). AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group II received saline, Group III allopurinol, Group IV allopurinol plus HBO and Group V HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS Serum amylase levels were lower in Groups III, IV and V compared to Group II (974 +/- 110, 384 +/- 40, 851 +/- 56, and 1664 +/- 234 U/L, respectively, P < 0.05, for all). Combining the two treatment options revealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations (13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P < 0.01). Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups III, IV and V compared to Group II (54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P < 0.05 for all). CONCLUSION The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.
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Eckerwall G, Olin H, Andersson B, Andersson R. Fluid resuscitation and nutritional support during severe acute pancreatitis in the past: what have we learned and how can we do better? Clin Nutr 2006; 25:497-504. [PMID: 16337067 DOI: 10.1016/j.clnu.2005.10.012] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2005] [Accepted: 10/25/2005] [Indexed: 01/22/2023]
Abstract
BACKGROUND/AIMS Severe acute pancreatitis is associated with microcirculatory impairment, increased gut permeability and metabolic changes. The aim of the present study was to evaluate initial fluid resuscitation and nutritional support versus outcome in patients with severe acute pancreatitis. METHODS All cases of acute pancreatitis admitted 1994-2003 were analyzed retrospectively. The inclusion criteria of severe acute pancreatitis were organ failure and/or local complications according to the Atlanta classification system. Mortality was used as outcome measure. RESULTS Ninty-nine patients were included in the study. The hospital mortality was 17%. Hypovolemia at arrival was found in 13% (13/99) and correlated with increased hospital mortality (P=0.009). During the first three days in average 11000+/-4100 ml of fluids and 1470+/-820 calories were administered. Total parental nutrition was given to 73% (69/95) and enteral nutrition served as a complement in 29% (28/95) of the patients. Hyperglycemia was seen in 61% (55/90) of the patients and insulin was administered to 53% (29/55) at an average glucose level of 19+/-3 mmol/l. The intake of oral food was reintroduced in average 15+/-9 days after admission and was interrupted in 17% (13/75) because of pain relapse. CONCLUSION A nutritional treatment regime in severe acute pancreatitis including a moderate and hypocaloric initial fluid resuscitation, parental nutrition as the preferred route for nutritional support and a non-strict glucose control, with an associated mortality of 17%, indicates several modes of improving outcome.
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Affiliation(s)
- Gunilla Eckerwall
- Department of Surgery, Lund University Hospital, S-221 85 Lund, Sweden
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Perez A, Ito H, Farivar RS, Cohn LH, Byrne JG, Rawn JD, Aranki SF, Zinner MJ, Tilney NL, Brooks DC, Ashley SW, Banks PA, Whang EE. Risk factors and outcomes of pancreatitis after open heart surgery. Am J Surg 2005; 190:401-5. [PMID: 16105526 DOI: 10.1016/j.amjsurg.2005.03.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2004] [Revised: 01/10/2005] [Indexed: 10/25/2022]
Abstract
BACKGROUND We sought to analyze the risk factors and natural history associated with post-cardiac surgery acute pancreatitis. METHODS Retrospective analysis of all patients having undergone cardiac surgery at our hospital between January 1, 1992, and October 1, 2001. RESULTS A total of 10,249 cardiac operations were performed. Thirty-nine (0.4%) patients developed postoperative pancreatitis. There was a higher incidence during the period spanning 1992 through 1996 than 1997 through 2001 (0.6% versus 0.2%, P< .05). Patients with pancreatitis had longer postoperative length of stay (51+/-5 days versus 10+/-1 days, P<.05) and a greater in-hospital mortality rate (28% versus 4%, P<.05) than patients who did not develop pancreatitis. A history of alcohol abuse, cardiac surgery performed during 1992 to 1996, increased cardiopulmonary bypass time, and increased cross-clamp time were independent risk factors for the development of pancreatitis. Multiple-organ failure was an independent predictor for death among patients with pancreatitis. CONCLUSIONS Although the frequency of post-cardiac surgery pancreatitis is diminishing, it is still associated with significant mortality.
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Affiliation(s)
- Alexander Perez
- Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Harvard Medical School, Boston, MA 02115, USA
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Abstract
Melatonin was thought to originate primarily from the pineal gland and to be secreted during the night, but recent studies revealed that gastrointestinal (GI) tract presents another, many times larger, source of melatonin that contributes significantly to the circulating concentration of this indole. Melatonin may exert a direct effect on GI tissues but its major influence on GI organs seems to occur indirectly, via the brain-gut axis including peripheral receptors, sensory afferent (vagal or sympathetic) pathways and central nervous system (CNS) acting on these organs via autonomic efferents and neuromediators. This article reviews and updates our experience with the fascinating molecule, as related to GI organs, with special focus on secretory activity of the stomach and pancreas and the maintenance of their tissue integrity. In addition to being released into the circulation, melatonin is also discharged into the gut lumen and this appears to be implicated in the postprandial stimulation of pancreatic enzyme secretion, mediated by melatonin-induced release of cholecystokinin, acting through entero-gastro-pancreatic reflexes. Although exerting certain differences in the mechanism of action on gastric and pancreatic secretory activities, melatonin derived from its precursor L-tryptophan, exhibits similar highly protective actions against the damage of both the stomach and the pancreas and accelerates the healing of chronic gastric ulcerations by stimulating the microcirculation and cooperating with arachidonate metabolites such as prostaglandins, with nitric oxide released from vascular endothelium, and/or sensory nerves and with their neuropeptides such as calcitonin gene related peptide. The beneficial effects of melatonin results in gastro- and pancreato-protection, prevents various forms of gastritis and pancreatitis through the activation of specific MT2-receptors and scavenges reactive oxygen species (ROS). Melatonin counteracts the increase in the ROS-induced lipid peroxidation and preserves, at least in part, the activity of key anti-oxidizing enzymes such as superoxide dismutase. It is proposed that melatonin should be considered as the agent exerting an important role in prevention of gastric and pancreatic damage and in accelerating healing of gastric ulcers.
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Affiliation(s)
- Jolanta Jaworek
- Department of Physiology, Jagiellonian University College of Medicine, Cracow, Poland
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Kuśnierz-Cabala B, Naskalski JW, Kedra B, Panek J. Comparison of sensitivity and specificity of serum poly-C avid ribonuclease activity and C-reactive protein concentration in detection of mild and severe acute pancreatitis. Clin Chem Lab Med 2005; 42:549-55. [PMID: 15202793 DOI: 10.1515/cclm.2004.093] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The aim of this study was to compare diagnostic performance of C-reactive protein (CRP) and poly-C avid ribonuclease (P-RNase) levels in the prediction of a severe clinical course of acute pancreatitis (AP). The study included 36 patients with mild and 20 with severe AP. CRP concentration was measured by an immunonephelometric method and P-RNase activity by the rate of polycytidylate hydrolysis at pH 7.8. At the time of admission, both P-RNase and CRP levels were significantly increased in all patients when compared to healthy subjects (29.2 vs. 18.7 U/l and 91.1 vs. 2.89 mg/l; p < 0.001). Up to days 3 and 4 a further increase in P-RNase was observed. On the other hand, the increase in CRP continued only through days 2 and 3 (p < 0.001). Severe acute pancreatitis (SAP) and mild acute pancreatitis (MAP) differed significantly with respect to P-RNase levels on all days studied; whereas CRP levels differed significantly on days 2-5 but did not differ at admission. Receiver operating characteristic (ROC) curve function analysis yielded the best sensitivity of SAP detection for P-RNase, equaling 72.2%, at the cut-off point value 65.3 U/l on day 3 after admission. The sensitivity of CRP for detection of SAP was 85.0% at 125.7 mg/l on the 2nd day after admission. Both parameters studied were significantly associated with the severity of the AP clinical course; however, on days 1 and 2 post-admission, P-RNase was more specific for detection of SAP than CRP (94.4% vs. 77.1% on the 1st day and 94.4% vs. 55.5% on the 2nd day). In conclusion, P-RNase has shown an excellent performance for early differentiation of acute necrotizing pancreatitis.
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Affiliation(s)
- Beata Kuśnierz-Cabala
- Department of Clinical Biochemistry, Collegium Medicum Jagiellonian University, Krakow, Poland.
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22
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Jaworek J, Konturek SJ, Tomaszewska R, Leja-Szpak A, Bonior J, Nawrot K, Palonek M, Stachura J, Pawlik WW. The circadian rhythm of melatonin modulates the severity of caerulein-induced pancreatitis in the rat. J Pineal Res 2004; 37:161-70. [PMID: 15357660 DOI: 10.1111/j.1600-079x.2004.00153.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Melatonin, an antioxidant, protects the pancreas against acute inflammation but, although this indole is released mainly at night, no study has been undertaken to determine circadian changes of plasma melatonin levels and the severity of acute pancreatitis. The aims of this study were: (a) to compare the severity of caerulein-induced pancreatitis (CIP) produced in the rat during the day and at the night, and (b) to assess the changes of plasma melatonin level and the activity of an antioxidative enzyme; superoxide dismutase (SOD), in the pancreas subjected to CIP during the day time and at night without or with administration of exogenous melatonin or its precursor; l-tryptophan. Rats were kept in 12 hr light/dark cycle. CIP was induced by subcutaneous infusion of caerulein (5 microg/kg/hr for 5 hr). Melatonin (5 or 25 mg/kg) or l-tryptophan (50 or 250 mg/kg) was given intraperitoneally 30 min prior to the start of CIP. CIP induced during the day time was confirmed by histological examination and manifested by pancreatic edema, and rises of amylase and lipase plasma activities (by 400 and 500%, respectively), whereas pancreatic SOD, pancreatic blood flow (PBF) and oxygen consumption by pancreatic tissue (VO(2)) were decreased by 70, 40 and 45%, respectively, as compared with the appropriate controls. All morphological and biochemical parameters of CIP induced at night were significantly less severe, compared with those recorded during the light phase. Plasma melatonin immunoreactivity was significantly higher during the night, than during the day, especially following administration of melatonin or its precursor, which reversed all manifestations of CIP. In conclusion, a circadian rhythm modulates the severity of CIP with a decrease of pancreatitis severity during the night compared with that at the day time and this may be due to the increased plasma level of melatonin and higher activity of SOD in the pancreas.
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Affiliation(s)
- Jolanta Jaworek
- Department of Medical Physiology, Faculty of Health Care, Medical Faculty, Jagiellonian University CM, 31-531 Krakow, Poland.
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23
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Hać S, Dobosz M, Kaczor J, Rzepko R. Influence of molecule CD 11b blockade on the course of acute ceruleine pancreatitis in rats. Exp Mol Pathol 2004; 77:57-65. [PMID: 15215051 DOI: 10.1016/j.yexmp.2003.12.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2003] [Indexed: 02/07/2023]
Abstract
Polymorphonuclear cells (PMN) activation is an essential step in acute pancreatitis (AP). We investigated the activation status of PMN, oxidative stress and pancreatic damage in early stage of experimental ceruleine pancreatitis in rats. The PMN action was modulated by monoclonal antibody CD 11b administration. The circulating WBC and polymorphonuclear cells count was reduced after AP induction. Chemiluminescence of whole blood PMN was remarkably reduced in AP group and increased after MoAb CD 11b administration. The CD 11b blockade significantly reduced the WBC infiltration and malondialdehyde (MDA) concentration within pancreatic gland. These data suggest that activated PMN are an important factor in early AP pathogenesis. Neutrophil aggregation within pancreatic gland modulated by monoclonal antibody CD11b contribute to the extent of injury during the early stage of ceruleine experimental pancreatitis in rats.
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Affiliation(s)
- Stanisław Hać
- Department of General Gastroenterological and Endocrine Surgery, Medical University of Gdañsk, Gdansk, Poland.
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24
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Abstract
AIM: To investigate the effects of rhubarb on severe acute pancreatitis (SAP) in rats.
METHODS: Severe acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 μg/kg body weight) plus 5-h restraint water-immersion stress. Rhubarb (75-150 mg/kg) was orally fed before the first cerulein injection. The degree of pancreatic edema, serum amylase level, local pancreatic blood flow (PBF), and histological alterations were investigated. The effects of rhubarb on pancreatic exocrine secretion in this model were evaluated by comparing with those of somatostatin.
RESULTS: In the Cerulein + Stress group, severe edema and diffuse hemorrhage in the pancreas were observed, the pancreatic wet weight (11.60 ± 0.61 g/Kg) and serum amylase (458 490 ± 43 100 U/L) were markedly increased (P < 0.01 vs control). In the rhubarb (150 mg/kg) treated rats, necrosis and polymorphonuclear neutrophil (PMN) infiltration in the pancreas were significantly reduced (P < 0.01), and a marked decrease (50%) in serum amylase levels was also observed (P < 0.01). PBF dropped to 38% (93 ± 5 mL/min per 100 g) of the control in the Cerulein + Stress group and partly recovered in the Cerulein + Stress + Rhubarb 150 mg group (135 ± 12 mL/min per 100 g) (P < 0.01). The pancreatic exocrine function was impaired in the SAP rats. The amylase levels of pancreatic juice were reduced in the rats treated with rhubarb or somatostatin, comparing with that of untreated SAP group. The bicarbonate concentration of pancreatic juice was markedly elevated only in the rhubarb-treated group (P < 0.01).
CONCLUSION: Rhubarb can exert protective effects on SAP, probably by inhibiting the inflammation of pancreas, improving pancreatic microcirculation, and altering exocrine secretion.
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Affiliation(s)
- Yu-Qing Zhao
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China
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25
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Vollmar B, Menger MD. Microcirculatory dysfunction in acute pancreatitis. A new concept of pathogenesis involving vasomotion-associated arteriolar constriction and dilation. Pancreatology 2004; 3:181-90. [PMID: 12817573 DOI: 10.1159/000070727] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Brigitte Vollmar
- Department of Experimental Surgery, University of Rostock, Germany.
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26
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Varadarajulu S, Noone T, Hawes RH, Cotton PB. Pancreatic duct stent insertion for functional smoldering pancreatitis. Gastrointest Endosc 2003; 58:438-41. [PMID: 14528225 DOI: 10.1067/s0016-5107(03)00025-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Some patients with smoldering pancreatitis in the absence of necrosis, pseudocyst, and ductal disruption experience unremitting abdominal pain caused by persistent pancreatic inflammation. Experience with the use of pancreatic duct stents in this patient population was reviewed. PATIENTS AND METHODS Data for 11 patients with smoldering pancreatitis who underwent ERCP with pancreatic duct stent placement were reviewed retrospectively. All patients had severe, daily pain that worsened with ingestion of food, had required narcotic analgesics for control of pain, had lost weight, and had persistently elevated serum levels of pancreatic enzymes as well as pancreatic inflammatory changes on CT (without necrosis or pseudocyst). Six patients were being treated with parenteral nutrition. OBSERVATIONS The mean duration of symptoms from the onset of pancreatitis until pancreatic duct stent insertion was 74 days (range 14-151 days). Stents were placed for a mean of 7 weeks (range 2-19 weeks). Pancreatic stent placement provided permanent pain relief in 10 (91%) patients within a mean of 9 days (range 3-20 days); one patient had persistent symptoms requiring celiac plexus blockade after 5 months. Parenteral nutrition and treatment with narcotic agents were discontinued for 10 patients within a mean of 15 days (range 7-39 days) after pancreatic duct insertion. CONCLUSIONS Smoldering pancreatitis may result from functional obstruction, possibly caused by edema or spasm, of the papillary orifice. Insertion of a stent into the pancreatic duct alleviates pain, enables early resumption of oral intake of food, and facilitates pancreatic duct drainage. It also may help to prevent complications arising from persistent pancreatic inflammation.
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Affiliation(s)
- Shyam Varadarajulu
- Digestive Disease Center, Medical University of South Carolina, Charleston, South Carolina, USA
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27
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Abstract
OBJECTIVE The pathophysiology of acute pancreatitis represents a diverse mix of congenital, hereditary, and acquired problems associated with or causing acute pancreatic inflammation. Acute pancreatitis is characterized by acinar cell injury that may involve regional and systemic inflammatory responses. The systemic manifestations of acute pancreatitis are responsible for the majority of pancreatitis-associated morbidity and are due to the actions of specific inflammatory cytokines. This report summarizes this pancreatic injury, the role of cytokines in the pathogenesis of acute pancreatitis, and the pancreatic healing response that follows. DESIGN A comprehensive literature review of experimental pancreatitis as well as reports of cytokine involvement and healing response during clinical pancreatitis was performed. RESULTS Histamine release, bradykinin generation, and cytokine release play a significant role during acute pancreatic inflammation. Following an experimental insult, there is rapid expression of tumor necrosis factor-alpha, interleukin-6, interleukin-1, and chemokines by pancreatic acinar cells and/or transmigrated leukocytes. Preventing the action of these mediators has a profound beneficial effect in experimental animals. Pancreatic fibrosis is a central histologic response after pancreatitis. Transient collagen deposition with acinar necrosis occurs in acute pancreatitis; in chronic pancreatitis, permanent and disorganized pancreatic fibrosis and parenchymal cell atrophy occur. CONCLUSIONS Inflammatory mediators are responsible for the systemic manifestations of acute pancreatitis and the associated distant organ dysfunction. After the acute injury, regeneration or pancreatic repair is characterized by decreased release of proinflammatory mediators and decreased infiltrating inflammatory cells. Differentiation and proliferation of pancreatic myofibroblasts or "stellate" cells may be responsible for increased extracellular matrix production. The predictable nature in which the inflammation and fibrosis are produced may stimulate novel approaches to disease treatment.
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Affiliation(s)
- David J Bentrem
- Department of Surgery, Northwestern University Feinberg School of Medicine, and Surgical Service, VA Chicago Health Care System, Illinois, USA
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28
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Kusnierz-Cabala B, Kedra B, Sierzega M. Current concepts on diagnosis and treatment of acute pancreatitis. Adv Clin Chem 2003; 37:47-81. [PMID: 12619705 DOI: 10.1016/s0065-2423(03)37006-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- B Kusnierz-Cabala
- Department of Clinical Biochemistry, Collegium, Medicum Jagiellonian University, Krakow, Poland
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29
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Keck T, Werner J, Schneider L, Gebhard MM, Klar E. Characterization of ischemia/reperfusion injury after pancreas transplantation and reduction by application of monoclonal antibodies against ICAM-1 in the rat. Surgery 2003; 134:63-71. [PMID: 12874584 DOI: 10.1067/msy.2003.187] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND Reperfusion injury contributes to early organ malfunction after transplantation. The aim of this study was to characterize the ischemia-reperfusion injury after pancreas transplantation and to evaluate the effect of monoclonal antibody therapy against ICAM-1. METHODS Twenty-five heterotopic pancreas transplantations were performed in syngenic rats in a no-touch technique. Microcirculation and leukocyte-endothelial interaction in the grafts were evaluated by intravital microscopy at 1 hour (I), 6 hours (II), 12 hours (III), and 24 hours (IV) after reperfusion, and 12 hours after reperfusion (V) in the therapeutic group. In (V) antibodies against ICAM-1 were applied as bolus at reperfusion and continuously for 6 hours. Next to intravital microscopy, histologic scores, myeloperoxidase levels, and ICAM-1 expression were determined. RESULTS Microcirculation was significantly reduced in capillaries and postcapillary venules in the time course after reperfusion (capillary: 0.96 +/- 0.08 mm/s [I] to 0.45 +/- 0.07 mm/s [IV] [P <.01]) and was improved significantly by therapy with ICAM-1 antibodies (0.98 +/- 0.06 mm/s, (P <.01). Leukocyte-endothelial interaction significantly increased 6 hours after reperfusion (II) (P <.01). These changes were paralleled by an increased endothelial expression of ICAM-1 in immunohistochemistry. Histologic evaluation showed increased inflammation at 12 hours after reperfusion (P <.01), which could be diminished by the administration of ICAM-1 antibodies (P <.05). CONCLUSION Increased endothelial expression of ICAM-1 after pancreas transplantation is positively correlated with microcirculatory impairment. Important steps of pancreatic inflammation take place approximately 6 hours after reperfusion. Prophylactic application of monoclonal antibodies against ICAM-1 reduces reperfusion injury and successfully prevents the occurrence of graft pancreatitis.
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Affiliation(s)
- Tobias Keck
- Department of General and Digestive Surgery, University of Freiburg, Germany
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30
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Goldenberg NM, Wang P, Glueck CJ. An observational study of severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride-lowering therapy when estrogens are given to women with and without familial hypertriglyceridemia. Clin Chim Acta 2003; 332:11-9. [PMID: 12763274 DOI: 10.1016/s0009-8981(03)00129-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND We assessed severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride-lowering therapy when estrogens were given to 56 women with and without familial hypertriglyceridemia. The 56 women had been consecutively referred to our center over a 3-year period because of triglycerides >400 mg/dl despite diet-drug treatment and/or a history of hypertriglyceridemic acute pancreatitis (AP). Of the 56 women, 17 had received estrogen replacement therapy (ERT), hormone replacement (HRT, n=6), or selective estrogen receptor modulators (SERM, n=1). METHODS After study at entry, in 56 women (median age, 52 years), 36 with familial hypertriglyceridemia, to lower triglycerides, estrogens and SERMs (hormone treatment, HT) were stopped; a very low fat diet (<15% of calories), gemfibrozil (1.2-1.5 mg/day), and omega-3-fatty acid (4-12 g/day) were started, with restudy 2-4 weeks later. RESULTS Of the 56 women, 24 (43%) were taking HT at entry, with median fasting triglycerides 1270 mg/dl in the HT group and 1087 mg/dl in the no-HT group. Seventeen women (30%) had a history of AP, nine of whom (53%) were/had been on HT at the development of AP. Significant positive correlates of triglycerides at entry in a stepwise regression model were hemoglobin A(1C) (partial r(2)=10.7%, p<0.05) and an interaction between estrogen use and familial hypertriglyceridemia (partial r(2)=15%, p=0.017). After 2-4 weeks on therapy, median triglycerides in the previous-HT group fell from 1270 to 284 mg/dl (p<0.0001) and in the no-HT group from 1087 to 326 mg/dl (p<0.0001). CONCLUSIONS Before starting HT, to avoid HT induced hypertriglyceridemic AP and exacerbation of overt or covert familial hypertriglyceridemia, triglycerides must be measured. HT is contraindicated in women with preexisting hypertriglyceridemia (triglycerides> or =500 mg/dl). Triglyceride-lowering diets and drugs often fail in the presence of HT and/or poorly controlled diabetes mellitus, but commonly succeed when HT is stopped and diabetes mellitus is tightly controlled.
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Affiliation(s)
- Naila M Goldenberg
- Cholesterol Center, Alliance Hospitals, ABC Building, 3200 Burnet Avenue, Cincinnati, OH 45229, USA
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31
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De La Torre Prados M, García AlcÁntara A, Soler García A, Fernández García I, Luque Fernández M, Merino Vega J. Pancreatitis aguda y base experimental en la respuesta fisiopatológica local y sistémica. Med Intensiva 2003. [DOI: 10.1016/s0210-5691(03)79875-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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32
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Abstract
Pancreatic microcirculatory disturbance plays an important role in the pathogenesis of acute pancreatitis, and it involves a series of changes including vasoconstriction, ischaemia, increased vascular permeability, impairment of nutritive tissue perfusion, ischaemia/reperfusion, leukocyte adherence, hemorrheological changes and impaired lymphatic drainage. Ischaemia possibly acts as an initiating factor of pancreatic microcirculatory injury in acute pancreatitis, or as an aggravating/continuing mechanism. The end-artery feature of the intralobular arterioles suggests that the pancreatic microcirculation is highly susceptible to ischaemia. Various vasoactive mediators, as bradykinin, platelet activating factor, endothelin and nitric oxide participate in the development of microcirculatory failure.
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Affiliation(s)
- Zong-Guang Zhou
- Department of Hepato-bilio-pancreatic Surgery & Institute of Microcirculation, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
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33
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Hantson P, Mahieu P. Pancreatic injury following acute methanol poisoning. JOURNAL OF TOXICOLOGY. CLINICAL TOXICOLOGY 2000; 38:297-303. [PMID: 10866330 DOI: 10.1081/clt-100100935] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
BACKGROUND Methanol ingestion is a cause of potentially life-threatening poisoning with numerous systemic manifestations. Clinicians may overlook the possibility of acute pancreatitis in this setting. The objective of this paper is to document the incidence of this complication in a series of 22 patients and to discuss the respective role of methanol and ethanol in its pathogenesis. CASE REPORT A 54-year-old woman developed acute necrotizing pancreatitis following acute methanol poisoning. She was treated by hemodialysis, ethanol infusion, and folinic acid, but, despite maximal supportive therapy, she died from multiple organ failure 54 hours after the ingestion. CASE SERIES In a series of 22 consecutive patients admitted with a diagnosis of acute methanol poisoning, we found evidence of pancreatic damage in 11 patients. The abnormalities were present from admission and before ethanol therapy in 7 cases and developed after ethanol therapy in 4 cases. Seven patients had a history of chronic ethanol abuse, but no patient had previously suffered from acute or chronic pancreatitis. Three patients presented moderate-to-severe acute pancreatitis according to clinical and radiological criteria and required aggressive supportive therapy including peritoneal dialysis. One patient died from the direct consequences of acute necrotizing pancreatitis and 2 fully recovered from this event. Three patients evolved to brain death; autopsy revealed hemorrhagic lesions in the pancreas in only 1 case. CONCLUSIONS Clinical, biological, and radiographic signs of acute pancreatic injury may be more common than previously realized. Acute methanol poisoning appears to produce pancreatic injury, although antidotal treatment with ethanol or prior chronic ethanol abuse may be contributing factors. Because ethanol treatment may complicate the pancreatic injury, fomepizole (4-methylpyrazole) may be the preferable antidote in acute methanol poisoning.
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Affiliation(s)
- P Hantson
- Department of Intensive Care, Cliniques Universitaires St.-Luc, Brussels, Belgium.
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34
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Gaisano HY. A hypothesis: SNARE-ing the mechanisms of regulated exocytosis and pathologic membrane fusions in the pancreatic acinar cell. Pancreas 2000; 20:217-26. [PMID: 10766446 DOI: 10.1097/00006676-200004000-00001] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
The pancreatic acinar cell has been a classic model to study regulated exocytosis occurring at the apical plasma membrane. The acinar cell is also an excellent model with which to study pathologic membrane fusion events, including aberrant zymogen granule fusion with the lysosome and basolateral exocytosis, which are the earliest cellular events of acute pancreatitis. However, despite much effort, little is known about the precise mechanisms that mediate these physiologic and pathologic membrane fusion events until recently. Over the past 5 years, there has been a major advance in the fundamental understanding of vesicle fusion based on the SNARE hypothesis. A basic tenet of the SNARE hypothesis is that the minimal machinery for membrane fusion is a cognate set of v- and t-SNAREs on opposing membranes. A corollary to this hypothesis is that these SNARE proteins are prevented from spontaneous assembly by clamping proteins. Here, the recent developments in the identification of cognate v- and t-SNAREs and clamping proteins are reviewed, which are strategically located to mediate these physiologic exocytic and pathologic fusion events in the pancreatic acinar cell.
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Affiliation(s)
- H Y Gaisano
- Department of Medicine and Physiology, University of Toronto, and University Health Network, Ontario, Canada.
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35
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Raper SE. Acute Pancreatitis Secondary to Dehydration: Case Report and Review of the Literature. Am Surg 1999. [DOI: 10.1177/000313489906501117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Recent reports have documented the potentially catastrophic consequences of dehydration induced by vigorous exercise in otherwise healthy individuals. A case of acute pancreatitis secondary to exercise-induced dehydration is presented, and the literature of dehydration-induced syndromes, both research and clinical, is reviewed. The goal of this case report is to heighten awareness of dehydration as a potential cause of acute pancreatitis.
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Affiliation(s)
- Steven E. Raper
- Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania
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36
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Sun Z, Wang X, Lasson A, Börjesson A, Leveau P, Haraldsen P, Andersson R. Roles of platelet-activating factor, interleukin-1beta and interleukin-6 in intestinal barrier dysfunction induced by mesenteric arterial ischemia and reperfusion. J Surg Res 1999; 87:90-100. [PMID: 10527709 DOI: 10.1006/jsre.1999.5746] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Platelet-activating factor (PAF), cytokines, proteases, and other factors are probably involved in the development of gut barrier dysfunction following intestinal ischemia and reperfusion (I/R), although the act underlying pathophysiological mechanisms has not yet been fully clarified. The aim of the present study was to clarify the relationship of intestinal barrier integrity to systemic levels of interleukin-1beta, interleukin-6, and protease inhibitor levels and local leukocyte accumulation in a rat model of intestinal ischemia for 40 min followed by 3 or 12 h reperfusion, with or without treatment with a PAF inhibitor. METHODS Myeloperoxidase (MPO) content in the small intestinal mucosa, serum levels of interleukin-1beta and -6, and plasma protease inhibitors, and intestinal endothelial and epithelial permeability were assessed, with or without treatment with the PAF antagonist lexipafant. RESULTS Intestinal I/R resulted in intestinal barrier dysfunction with pronounced plasma leakage to the intestinal lumen, the leakage being aggravated following a longer reperfusion period. Proteolytic plasma activity was evident by low levels of the plasma protease inhibitors measured. MPO content increased significantly after I/R, as did serum levels of interleukin-1beta and -6, without difference between the two periods of reperfusion. Treatment with the PAF inhibitor lexipafant partly, though not fully, restored the changes caused by I/R. CONCLUSION PAF seems to be involved in the release of cytokines, such as interleukin-1 and -6, consumption of protease inhibitors, and impaired intestinal barrier integrity seen following intestinal I/R. Treatment with a PAF antagonist was effective in restoring the changes caused by intestinal I/R, though not reaching complete normal levels.
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Affiliation(s)
- Z Sun
- Department of Surgery, Lund University Hospital, Lund, Sweden
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Bonham MJ, Abu-Zidan FM, Simovic MO, Sluis KB, Wilkinson A, Winterbourn CC, Windsor JA. Early ascorbic acid depletion is related to the severity of acute pancreatitis. Br J Surg 1999; 86:1296-301. [PMID: 10540137 DOI: 10.1046/j.1365-2168.1999.01182.x] [Citation(s) in RCA: 50] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Ascorbic acid (AA) is an important endogenous antioxidant in plasma and has been shown to be decreased at the time of hospital admission in patients with acute pancreatitis. The aim of this study was to determine whether plasma AA concentration continues to decrease after admission and whether the extent of decrease is related to the severity of pancreatitis. METHODS Consecutive patients with mild (n = 62) and severe (n = 23) acute pancreatitis had plasma AA concentration measured on the day of recruitment and on days 2 and 5 by high-performance liquid chromatography. RESULTS The plasma AA concentration in patients with acute pancreatitis was significantly less than that in normal volunteers on days 0, 2 and 5 (P < 0.0001) and this was more marked in those with severe disease. There was a decrease in plasma AA concentration from day 0 to day 2 in patients with mild (P < 0.0001) and severe (P = 0.0005) pancreatitis, and from day 2 to day 5 in patients with severe pancreatitis (P = 0.023). CONCLUSION Endogenous plasma AA continues to decrease over the first 5 days in hospital and the extent is related to the severity of acute pancreatitis. Presented to a meeting of the Australasian Surgical Research Society, Auckland, New Zealand, August 1995 and published in abstract form as Aust N Z J Surg 1996; 66: 243
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Affiliation(s)
- M J Bonham
- Pancreatitis Research Group, Department of Surgery, Faculty of Medicine and Health Science, University of Auckland, New Zealand
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von Dobschuetz E, Hoffmann T, Engelschalk C, Messmer K. Effect of diaspirin cross-linked hemoglobin on normal and postischemic microcirculation of the rat pancreas. THE AMERICAN JOURNAL OF PHYSIOLOGY 1999; 276:G1507-14. [PMID: 10362655 DOI: 10.1152/ajpgi.1999.276.6.g1507] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/12/2023]
Abstract
Microcirculatory alterations with reduced nutritive supply to the pancreas could be the cause of hyperamylasemia, which occurs in some patients receiving the vasoactive oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) in clinical studies. Therefore, the effects of DCLHb on rat pancreas microcirculation were evaluated. Anesthetized Sprague-Dawley rats received one of the following treatments during baseline conditions (n = 7 rats/group): 10% hydroxyethyl starch (HAES) (0.4 ml/kg), DCLHb (400 mg/kg), or DCLHb (1,400 mg/kg). After 1 h of complete, reversible pancreatic ischemia, other animals received 10% HAES (0.4 ml/kg) or DCLHb (400 mg/kg) during the onset of reperfusion. The number of red blood cell-perfused capillaries (functional capillary density, FCD) and the level of leukocyte adherence in postcapillary venules in the pancreas were assessed by means of intravital microscopy during 2 h after treatment. In the nonischemic groups, FCD was 18% greater after DCLHb (1,400 mg/kg) than after 10% HAES treatment without any increase in leukocyte adherence. In the inschemia-reperfusion (I/R) 10% HAES group, FCD was significantly (P < 0.05) lowered, leukocyte adherence enhanced, and mean arterial pressure (MAP) reduced by 31% compared with nonischemic animals. DCLHb treatment in the I/R group resulted in a slight increase in FCD, a significant (P < 0.05) reduction of leukocyte adherence, and a complete restoration of MAP compared with the animals of the I/R control group. Thus our data provide no evidence for a detrimental effect on the pancreatic microcirculation or an enhanced risk of postischemic pancreatitis by DCLHb.
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Affiliation(s)
- E von Dobschuetz
- Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians University, D-81366 Munich, Germany.
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Suazo-Baráhona J, Carmona-Sánchez R, Robles-Díaz G, Milke-García P, Vargas-Vorácková F, Uscanga-Domínguez L, Peláez-Luna M. Obesity: a risk factor for severe acute biliary and alcoholic pancreatitis. Am J Gastroenterol 1998; 93:1324-8. [PMID: 9707059 DOI: 10.1111/j.1572-0241.1998.442_l.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE In this study we evaluate the association between obesity and complication development in patients with a first-attack acute pancreatitis (AP), and investigate the influence of comorbid factors on this association. METHODS Medical records of 150 patients with AP were reviewed. General data, AP etiology, admission AP prognostic criteria, and occurrence of complications were recorded. Patients were classified according to body mass index (BMI) as obese (BMI > 25 kg/m2) and nonobese (BMI < or = 25 kg/m2). RESULTS Prevalence of obesity was 57%. Thirty-eight percent of the obese patients developed complications as compared with 21% of the nonobese (RR=1.74; 95% CI, 1-2.9). The risk for severe AP increased according to the degree of obesity. Pancreatic and peripancreatic necrosis was more common in obese patients (17.6% vs 6%), as was the incidence of infectious complications. The risk for severe AP was highest in obese patients with either alcoholic (RR=5.3; 95% CI, 1.2-23) or biliary etiology (RR=5.2, 95% CI, 1-26). CONCLUSION Obesity may predispose to a complicated course of AP, especially if it is secondary to alcohol or gallstones. Further studies are needed to establish the precise prognostic value of obesity in AP, as well as the pathogenic mechanisms involved in the process.
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Affiliation(s)
- J Suazo-Baráhona
- Department of Gastroenterology, Instituto Nacional de la Nutrición Salvador Zubirán, México City, México
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Bonham MJ, Abu-Zidan FM, Simovic MO, Windsor JA. Gastric intramucosal pH predicts death in severe acute pancreatitis. Br J Surg 1998. [PMID: 9448612 DOI: 10.1046/j.1365-2168.1997.02852.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND This study tested the hypothesis that gastric intramucosal pH (pHi) can predict death in severe acute pancreatitis. METHODS Seventeen consecutive patients with predicted severe acute pancreatitis were studied prospectively. Four died from complications related to pancreatitis. Gastric pHi was measured by nasogastric tonometry at least every 12 h for the first 48 h after admission and then on a daily basis during the first week. RESULTS The lowest pHi recorded during the first 48 h was significantly less in those admitted to the intensive care unit than that in those who remained on the surgical ward (P = 0.0015) and in nonsurvivors compared with the survivors (P = 0.009). A receiver-operator characteristic curve defined a pHi of 7.25 as the optimal cut-off point to predict death (sensitivity 100 per cent, specificity 77 per cent, overall predictive value 82 per cent). CONCLUSION These results suggest that splanchnic ischaemia may be an important determinant of outcome in patients with severe acute pancreatitis.
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Affiliation(s)
- M J Bonham
- Department of Surgery, Faculty of Medicine and Health Sciences, University of Auckland, New Zealand
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Bonham MJ, Abu-Zidan FM, Simovic MO, Windsor JA. Gastric intramucosal pH predicts death in severe acute pancreatitis. Br J Surg 1998. [PMID: 9448612 DOI: 10.1002/bjs.1800841208] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND This study tested the hypothesis that gastric intramucosal pH (pHi) can predict death in severe acute pancreatitis. METHODS Seventeen consecutive patients with predicted severe acute pancreatitis were studied prospectively. Four died from complications related to pancreatitis. Gastric pHi was measured by nasogastric tonometry at least every 12 h for the first 48 h after admission and then on a daily basis during the first week. RESULTS The lowest pHi recorded during the first 48 h was significantly less in those admitted to the intensive care unit than that in those who remained on the surgical ward (P = 0.0015) and in nonsurvivors compared with the survivors (P = 0.009). A receiver-operator characteristic curve defined a pHi of 7.25 as the optimal cut-off point to predict death (sensitivity 100 per cent, specificity 77 per cent, overall predictive value 82 per cent). CONCLUSION These results suggest that splanchnic ischaemia may be an important determinant of outcome in patients with severe acute pancreatitis.
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Affiliation(s)
- M J Bonham
- Department of Surgery, Faculty of Medicine and Health Sciences, University of Auckland, New Zealand
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