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Sartim MA, Raimunda da Costa M, Bentes KO, Mwangi VI, Pinto TS, Oliveira S, Mota Cordeiro JS, Wilson do Nascimento Corrêa J, Ferreira JMBB, Cardoso de Melo G, Sachett J, Monteiro WM. Myocardial injury and its association with venom-induced coagulopathy following Bothrops atrox snakebite envenomation. Toxicon 2025; 258:108312. [PMID: 40058470 DOI: 10.1016/j.toxicon.2025.108312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 02/18/2025] [Accepted: 03/05/2025] [Indexed: 03/16/2025]
Abstract
BACKGOUND In Brazil, the highest incidences of snakebite envenomation (SBE) occur in the Amazon region, caused mostly by Bothrops atrox. Among the effects of envenomation, cardiac alterations are not a frequent outcome but are highly linked to severe cases. OBJECTIVE The present study investigated the serum profile of cardiac injury markers (fatty acid binding protein 3 - H-FABP3, N-terminal type B natriuretic peptide - NTproBNP, creatine kinase-MB - CPK-MB, and troponin I) following Bothrops SBEs and their association with venom-induced coagulopathy. METHODS Plasma markers were evaluated from blood collected at admission (before antivenom - T0) and 48h after antivenom (T48) from 80 B. atrox SBE patients treated at a tertiary hospital in Manaus, Brazilian Amazon, and 20 healthy donors. RESULTS Markers were found increased, above reference range or compared to sex- and age-matched healthy controls, including FABP3 in at least 98.7% of patients, Troponin I 12.5%, and CK-MB in 8.8%. Regarding correlations to coagulation markers, alpha 2-antiplasmin concentrations were negatively correlated with FABP3 levels (T0), whereas FDP, tissue factor, and plasma factor VII levels were positively correlated with troponin I concentrations. Moreover, the group of patients with increased troponin I levels presented significantly higher FDP concentrations, factor VII levels, and risk for systemic bleeding at T0, whereas higher D-dimer concentrations at T48. CONCLUSIONS Our findings show that Bothrops SBE is responsible for myocardial injury, although not associated with severe outcomes, and its directly associated to venom-induced coagulopathy, indicating troponin-I and FABP3 as possible markers to screen patients for more detailed cardiac alterations.
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Affiliation(s)
- Marco Aurélio Sartim
- Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus, Brazil; Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
| | - Maria Raimunda da Costa
- Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus, Brazil; Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
| | - Karolaine Oliveira Bentes
- Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil
| | - Victor Irungu Mwangi
- Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil
| | - Thiago Serrão Pinto
- Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus, Brazil; Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil
| | - Samella Oliveira
- Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil
| | - Jady Shayene Mota Cordeiro
- Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil
| | | | | | - Gisely Cardoso de Melo
- Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil
| | - Jacqueline Sachett
- Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil
| | - Wuelton Marcelo Monteiro
- Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus, Brazil; Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil; Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil.
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Elsayed EA, Eweda SA, El-Morsy SA. Assessment of the role of N-terminal pro-B-type natriuretic peptide as a predictive biomarker of mortality in acute aluminum phosphide poisoning. Biomarkers 2024; 29:376-383. [PMID: 39234754 DOI: 10.1080/1354750x.2024.2400910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 08/31/2024] [Indexed: 09/06/2024]
Abstract
BACKGROUND In Egypt, aluminum phosphide (ALP) is a known lethal poison due to its cardiotoxicity. This study aimed to evaluate the predictive ability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality in ALP-poisoned patients. METHODS This prospective study was conducted on patients with ALP poisoning admitted to the Poison Control Center Ain Shams University Hospitals between July and December 2022. Upon admission, all patients were followed up and had their levels of NT-proBNP, troponin I (cTnI), and creatine kinase myocardial band (CK-MB) analyzed. RESULTS Thirty patients were enrolled in the study and were divided into survivors and non-survivors. The initial NT-proBNP levels were significantly higher among non-survivors in contrast to the initial cTnI and CK-MB levels. The study identified that the best cutoff point of NT-proBNP for predicting mortality was ≥72 pg/ml, with AUC (0.869). CONCLUSION It can be concluded that NT-proBNP can serve as an early predictor of mortality in ALP poisoning.
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Affiliation(s)
- Emad Ahmed Elsayed
- Department of Forensic Medicine and Clinical toxicology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sarah Atef Eweda
- Department of Forensic Medicine and Clinical toxicology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sarah Ahmad El-Morsy
- Department of Forensic Medicine and Clinical toxicology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Li Y, Li Y. Quantitative Fluorescent Lateral Flow Strip Sensor for Myocardial Infarction Using Purity-Color Upconversion Nanoparticles. Inorg Chem 2024; 63:5185-5198. [PMID: 38451175 DOI: 10.1021/acs.inorgchem.4c00169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2024]
Abstract
Acute myocardial infarction is a serious cardiovascular disease and poses significant risks to human health. Its early diagnosis and real-time detection are of great importance. Herein, we design a low-cost device that has a high sensitivity of cTnT and cTnI detection. Dual-color upconversion nanoparticles (UCNPs) are prepared as probes, which not only have high-purity red upconversion luminescence (UCL) under 980 or 808 nm excitation but also achieve good temperature sensing. Temperature-dependent multicolor emission excitation is obtained, and the color turns from white to orange and red with increasing temperature. In particular, the maximum SR and SA values based on nonthermally coupled levels are 4.76% K-1 and 8.6% K-1, which are higher than those based on thermally coupled levels. With the UCNPs-based lateral flow strip (LFS), the specific detection of cTnI and cTnT antigens in samples is achieved with a detection limit of 0.001 ng/mL, which is 1 order of magnitude lower than that of their clinical cutoff. The UCNPs-LFS device has a low-cost laser diode and a simplified laser and permits a mobile-phone camera to collect the results, which has an important influence on the field of biomarker sensing.
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Affiliation(s)
- Yuemei Li
- Xiamen Key Laboratory of Cardiovascular Disease, Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361005, China
| | - Yongmei Li
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, No. 6 Huanrui North Road, Ruijing Street, Beichen District, Tianjin 300134, China
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Gulmez AO, Aydin S. Utility of cardiac bioenzymes in predicting cardiovascular outcomes in SARS-CoV-2. World J Virol 2023; 12:132-135. [PMID: 37033145 PMCID: PMC10075052 DOI: 10.5501/wjv.v12.i2.132] [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: 10/19/2022] [Revised: 11/30/2022] [Accepted: 01/05/2023] [Indexed: 03/21/2023] Open
Abstract
The relationship between coronavirus disease-19 (COVID-19) and cardiovascular diseases has been an important issue. Therefore, cardiac biomarkers and cardiac imaging have an important place in the diagnostic phase. It is important to know the relationship of biomarkers in COVID-19 so that we can understand the diagnosis of the disease, the predicted course and results after diagnosis.
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Affiliation(s)
- Ali Osman Gulmez
- Department of Radiology, Erzincan University, Erzincan 24100, Turkey
| | - Sonay Aydin
- Department of Radiology, Erzincan University, Erzincan 24100, Turkey
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Omar SI, Keasar C, Ben-Sasson AJ, Haber E. Protein Design Using Physics Informed Neural Networks. Biomolecules 2023; 13:biom13030457. [PMID: 36979392 PMCID: PMC10046838 DOI: 10.3390/biom13030457] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/16/2023] [Accepted: 02/27/2023] [Indexed: 03/06/2023] Open
Abstract
The inverse protein folding problem, also known as protein sequence design, seeks to predict an amino acid sequence that folds into a specific structure and performs a specific function. Recent advancements in machine learning techniques have been successful in generating functional sequences, outperforming previous energy function-based methods. However, these machine learning methods are limited in their interoperability and robustness, especially when designing proteins that must function under non-ambient conditions, such as high temperature, extreme pH, or in various ionic solvents. To address this issue, we propose a new Physics-Informed Neural Networks (PINNs)-based protein sequence design approach. Our approach combines all-atom molecular dynamics simulations, a PINNs MD surrogate model, and a relaxation of binary programming to solve the protein design task while optimizing both energy and the structural stability of proteins. We demonstrate the effectiveness of our design framework in designing proteins that can function under non-ambient conditions.
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Affiliation(s)
| | - Chen Keasar
- Department of Computer Science, Ben Gurion University of the Negev, Be’er Sheva 84105, Israel
| | - Ariel J. Ben-Sasson
- Independent Researcher, Haifa 3436301, Israel
- Correspondence: (A.J.B.-S.); (E.H.)
| | - Eldad Haber
- Department of Earth Ocean and Atmospheric Sciences, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
- Correspondence: (A.J.B.-S.); (E.H.)
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Investigation of doxorubicin combined with ciprofloxacin-induced cardiotoxicity: from molecular mechanism to fundamental heart function. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2022:10.1007/s00210-022-02331-2. [DOI: 10.1007/s00210-022-02331-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/07/2022] [Indexed: 11/25/2022]
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Tumer KC, Safak T. Serum cardiac troponin I concentration increases in sheep with uterine torsion. Small Rumin Res 2022. [DOI: 10.1016/j.smallrumres.2022.106784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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The Future of Biomarkers in Veterinary Medicine: Emerging Approaches and Associated Challenges. Animals (Basel) 2022; 12:ani12172194. [PMID: 36077913 PMCID: PMC9454634 DOI: 10.3390/ani12172194] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 08/20/2022] [Accepted: 08/22/2022] [Indexed: 11/30/2022] Open
Abstract
Simple Summary In this review we seek to outline the role of new technologies in biomarker discovery, particularly within the veterinary field and with an emphasis on ‘omics’, as well as to examine why many biomarkers-despite much excitement-have not yet made it to clinical practice. Further we emphasise the critical need for close collaboration between clinicians, researchers and funding bodies and the need to set clear goals for biomarker requirements and realistic application in the clinical setting, ensuring that biomarker type, method of detection and clinical utility are compatible, and adequate funding, time and sample size are available for all phases of development. Abstract New biomarkers promise to transform veterinary practice through rapid diagnosis of diseases, effective monitoring of animal health and improved welfare and production efficiency. However, the road from biomarker discovery to translation is not always straightforward. This review focuses on molecular biomarkers under development in the veterinary field, introduces the emerging technological approaches transforming this space and the role of ‘omics platforms in novel biomarker discovery. The vast majority of veterinary biomarkers are at preliminary stages of development and not yet ready to be deployed into clinical translation. Hence, we examine the major challenges encountered in the process of biomarker development from discovery, through validation and translation to clinical practice, including the hurdles specific to veterinary practice and to each of the ‘omics platforms–transcriptomics, proteomics, lipidomics and metabolomics. Finally, recommendations are made for the planning and execution of biomarker studies with a view to assisting the success of novel biomarkers in reaching their full potential.
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Han Y, Duan B, Wu J, Zheng Y, Gu Y, Cai X, Lu C, Wu X, Li Y, Gu X. Analysis of Time Series Gene Expression and DNA Methylation Reveals the Molecular Features of Myocardial Infarction Progression. Front Cardiovasc Med 2022; 9:912454. [PMID: 35811717 PMCID: PMC9263976 DOI: 10.3389/fcvm.2022.912454] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 05/25/2022] [Indexed: 11/13/2022] Open
Abstract
Myocardial infarction (MI) is one of the deadliest diseases in the world, and the changes at the molecular level after MI and the DNA methylation features are not clear. Understanding the molecular characteristics of the early stages of MI is of significance for the treatment of the disease. In this study, RNA-seq and MeDIP-seq were performed on heart tissue from mouse models at multiple time points (0 h, 10 min, 1, 6, 24, and 72 h) to explore genetic and epigenetic features that influence MI progression. Analysis based on a single point in time, the number of differentially expressed genes (DEGs) and differentially methylated regions (DMRs) increased with the time of myocardial infarction, using 0 h as a control group. Moreover, within 10 min of MI onset, the cells are mainly in immune response, and as the duration of MI increases, apoptosis begins to occur. Analysis based on time series data, the expression of 1012 genes was specifically downregulated, and these genes were associated with energy metabolism. The expression of 5806 genes was specifically upregulated, and these genes were associated with immune regulation, inflammation and apoptosis. Fourteen transcription factors were identified in the genes involved in apoptosis and inflammation, which may be potential drug targets. Analysis based on MeDIP-seq combined with RNA-seq methodology, focused on methylation at the promoter region. GO revealed that the downregulated genes with hypermethylation at 72 h were enriched in biological processes such as cardiac muscle contraction. In addition, the upregulated genes with hypomethylation at 72 h were enriched in biological processes, such as cell-cell adhesion, regulation of the apoptotic signaling pathway and regulation of angiogenesis. Among these genes, the Tnni3 gene was also present in the downregulated model. Hypermethylation of Tnni3 at 72 h after MI may be an important cause of exacerbation of MI.
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Affiliation(s)
- Yuru Han
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Baoyu Duan
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Jing Wu
- School of Nursing, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yanjun Zheng
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Yinchen Gu
- School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Xiaomeng Cai
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Changlian Lu
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Xubo Wu
- School of Nursing, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Xubo Wu
| | - Yanfei Li
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China
- Yanfei Li
| | - Xuefeng Gu
- Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China
- School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China
- School of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, China
- *Correspondence: Xuefeng Gu
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Jörres M, Gunga HC, Steinach M. Physiological Changes, Activity, and Stress During a 100-km-24-h Walking-March. Front Physiol 2021; 12:640710. [PMID: 33776795 PMCID: PMC7991843 DOI: 10.3389/fphys.2021.640710] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 01/27/2021] [Indexed: 11/13/2022] Open
Abstract
Background Long-endurance exercises like ultramarathons are known to elicit various metabolic and physiological changes in the human body. However, little is known about very long-duration exercise at low intensities regarding healthy human subjects. Aim The purpose of this study was to evaluate changes in body composition and metabolism in long-endurance but low-intensity events. Methods Twenty-five male and 18 female healthy recreational athletes (age 34.6 ± 8.8 years; BMI: 22.4 ± 2.0 kg/m2) of the "100 km Mammutmarsch" were recruited for participation during the events in 2014-2016. Other than classical ultramarathons, the "Mammutmarsch" is a hiking event, in which participants were required to walk but not run or jog. It was expected to complete the 100-km distance within 24 h, resulting in a calculated mean speed of 4.17 km/h, which fits to the mean speed observed (4.12 ± 0.76 km/h). As not all participants reached the finish line, comparison of finishers (FIN, n = 11) and non-finishers (NON, n = 21) allowed differential assessment of performance. Body composition measured through bioelectrical impedance analysis (BIA) was determined pre- and post-event, and serum samples were taken pre-event, at 30, 70, and 100 km to determine NT-pro-BNP, troponin T, C-reactive protein (CRP), cortisol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, total cholesterol, total creatine kinase (CK), CK-MB, aminotransferase (AST), ALT, and sodium levels. Nineteen participants wore actimeter armbands (SenseWear®) to gain information about body activity and exercise intensity [metabolic equivalent of task (MET)]. Sixteen participants wore mobile heart rate monitors to assess mean heart rate during the race. Serum parameter alterations over the course of the race were analyzed with mixed-effects ANOVA and additional t-tests. All serum parameters were analyzed for correlation concerning different MET levels, speed, age, BMI, baseline NT-pro-BNP, mean heart rate during the race, and sex with linear regression analysis. Results We found significant elevations for muscle and cardiac stress markers (CRP, CK, CK-MB, AST, ALT, cortisol, and NT-pro-BNP) as well as decreasing markers of lipid metabolism (cholesterol, triglycerides, LDL). Although the intensity level demanded from our participants was low compared with other studies on (ultra-) marathons, the alteration of tested parameters was similar to those of high-intensity exercise, e.g., NT-pro-BNP showed a fourfold increase (p < 0.01) and LDL decreased by 20% (p = 0.05). Besides the duration of exercise, age, BMI, training status, and sex are relevant parameters that influence the elevation of stress factors. Notably, our data indicate that NT-pro-BNP might be a marker for cardiovascular fitness also in healthy adults. Conclusion This low-intensity long-endurance walk evoked a strong systemic reaction and large cell stress and shifted to a favorable lipid profile, comparable to higher intensity events. Despite increasing cardiac stress parameters, there were no indications of cardiac cell damage. Remarkably, the duration seems to have a greater influence on stress markers and metabolism than intensity.
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Affiliation(s)
- Marc Jörres
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Physiology, Center for Space Medicine and Extreme Environments, Berlin, Germany
| | - Hanns-Christian Gunga
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Physiology, Center for Space Medicine and Extreme Environments, Berlin, Germany
| | - Mathias Steinach
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Physiology, Center for Space Medicine and Extreme Environments, Berlin, Germany
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Smith JS, Varga A, Schober KE. Comparison of Two Commercially Available Immunoassays for the Measurement of Bovine Cardiac Troponin I in Cattle With Induced Myocardial Injury. Front Vet Sci 2020; 7:531. [PMID: 33062647 PMCID: PMC7481330 DOI: 10.3389/fvets.2020.00531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 07/08/2020] [Indexed: 11/23/2022] Open
Abstract
Background: Multiple cardiac troponin I (cTnI) immunoassays are commercially available. Overall, assays have not been standardized, and inter-assay differences in the detection of the analyte cardiac troponin I can be clinically relevant. Objective: To compare the diagnostic accuracy of the commercially available Abbott i-STAT®1 cTnI immunoassay (i-STAT) and the previously validated ADVIA Centaur TnI-Ultra immunoassay (Centaur) in cattle. Hypothesis: There will be significant differences in bovine serum cTnI results measured by the Centaur and i-STAT methods. Animals: Ten dairy cows with experimentally induced myocardial injury due to monensin administration. Thirty apparently healthy dairy cows with no history of monensin exposure served as controls. Methods: Blood was collected at various time points after administration of a single dose of monensin (20 to 50 mg/kg) via orogastric tube. A total of 112 blood samples were collected. Cardiac TnI concentration was analyzed with the two methods and the association between methods analyzed via linear regression. Bland-Altman analysis to evaluate agreement between methods was performed on samples divided into groups (cTnI < 1.0 ng/mL and cTnI ≥ 1.0 ng/mL). Results: Analyzer results were linearly correlated with each other (R2 = 0.931). Samples with cTnI concentrations <1.0 ng/mL had a bias of −0.13 ± 0.20 ng/mL and samples with cTnI concentrations >1.0 ng/mL had a bias of −9.81 ± 13.26 ng/mL. Conclusions and clinical importance: The results of this study reveal that cTnI concentrations determined with the i-STAT are systematically lower compared to the concentrations determined by the Centaur.
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Affiliation(s)
- Joe S Smith
- Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.,Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Anita Varga
- Gold Coast Veterinary Service and Consulting, Esparto, CA, United States
| | - Karsten E Schober
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, United States
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Combining Novel Biomarkers for Risk Stratification of Two-Year Cardiovascular Mortality in Patients with ST-Elevation Myocardial Infarction. J Clin Med 2020; 9:jcm9020550. [PMID: 32085400 PMCID: PMC7073894 DOI: 10.3390/jcm9020550] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Accepted: 02/13/2020] [Indexed: 12/19/2022] Open
Abstract
ST-elevation myocardial infarction (STEMI) is one of the main reasons for morbidity and mortality worldwide. In addition to the classic biomarker NT-proBNP, new biomarkers like ST2 and Pentraxin-3 (Ptx-3) have emerged as potential tools in stratifying risk in cardiac patients. Indeed, multimarker approaches to estimate prognosis of STEMI patients have been proposed and their potential clinical impact requires investigation. In our study, in 147 patients with STEMI, NT-proBNP as well as serum levels of ST2 and Ptx-3 were evaluated. During two-year follow-up (FU; 734.2 ± 61.2 d) results were correlated with risk for cardiovascular mortality (CV-mortality). NT-proBNP (HR = 1.64, 95% CI = 1.21–2.21, p = 0.001) but also ST2 (HR = 1.000022, 95% CI = 1.00–1.001, p < 0.001) were shown to be reliable predictors of CV-mortality, while the highest predictive power was observed with Ptx-3 (HR = 3.1, 95% CI = 1.63–5.39, p < 0.001). When two biomarkers were combined in a multivariate Cox regression model, relevant improvement of risk assessment was only observed with NT-proBNP+Ptx-3 (AIC = 209, BIC = 214, p = 0.001, MER = 0.75, MEV = 0.64). However, the highest accuracy was seen using a three-marker approach (NT-proBNP + ST2 + Ptx-3: AIC = 208, BIC = 214, p < 0.001, MER = 0.77, MEV = 0.66). In conclusion, after STEMI, ST2 and Ptx-3 in addition to NT-proBNP were associated with the incidence of CV-mortality, with multimarker approaches enhancing the accuracy of prediction of CV-mortality.
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Natarajan S, Su F, Jayaraj J, Shah MII, Huang Y. A paper microfluidics-based fluorescent lateral flow immunoassay for point-of-care diagnostics of non-communicable diseases. Analyst 2019; 144:6291-6303. [PMID: 31549693 DOI: 10.1039/c9an01382b] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
In the emergency diagnosis of patients, acute myocardial infarction (AMI) is always time-consuming to diagnose, and the process requires multiple laboratory procedures, expensive equipment and skilled workers. Herein, we developed an easy-to-use, low-cost and portable fluorescent lateral flow immunoassay based on paper microfluidics for the point-of-care diagnostics of non-communicable diseases. The fluorescent lateral flow immunoassay can produce results in less than 10 minutes, and the limit of detection (LOD) is 0.019 ng ml-1. The slope was linear from 0 to 100 ng ml-1; the equation is y = 0.0342e2.1181x and R2 = 0.9618, which are distinctive features that ensure maximum amplification of the signal and recording of quantitative values by an analyser. The detection sensitivity showed an exceptional increase to 0.01 ng ml-1. Compared with conventional bioassay readers, our analyser shows some advantages to easily, clearly and effectively read data. The present point-of-care test for cardiac troponin I decreases the turnaround time and has a high coefficient of variation even at lower concentrations of troponin. So, the development of lateral flow assay-based point-of-care assays with higher analytical performance for real world samples can decrease the rule-out time for AMI in emergency departments and other fields.
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Affiliation(s)
- Satheesh Natarajan
- College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, Zhejiang - 311121, China.
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14
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Diagnostic Roles of Postmortem cTn I and cTn T in Cardiac Death with Special Regard to Myocardial Infarction: A Systematic Literature Review and Meta-Analysis. Int J Mol Sci 2019; 20:ijms20133351. [PMID: 31288395 PMCID: PMC6651768 DOI: 10.3390/ijms20133351] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 06/29/2019] [Accepted: 07/06/2019] [Indexed: 02/06/2023] Open
Abstract
Background: Cardiac troponin I (cTn I) and cardiac troponin T (cTn T) are currently widely used as diagnostic biomarkers for myocardial injury caused by ischemic heart diseases in clinical and forensic medicine. However, no previous meta-analysis has summarized the diagnostic roles of postmortem cTn I and cTn T. The aim of the present study was to meta-analyze the diagnostic roles of postmortem cTn I and cTn T for cardiac death in forensic medicine, present a systematic review of the previous literature, and determine the postmortem cut-off values of cTn I and cTn T. Methods: We searched multiple databases for the related literature, performed a meta-analysis to investigate the diagnostic roles of postmortem cardiac troponins, and analyzed the receiver operating characteristic (ROC) curve to determine their postmortem cut-off values. Results and Conclusions: The present meta-analysis demonstrated that postmortem cTn I and cTn T levels were increased in pericardial fluid and serum in cardiac death, especially in patients with acute myocardial infarction (AMI). We determined the postmortem cut-off value of cTn I in the pericardial fluid at 86.2 ng/mL, cTn I in serum at 9.5 ng/mL, and cTn T in serum at 8.025 ng/mL.
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15
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Neves AL, Henriques-Coelho T, Leite-Moreira A, Areias JC. Cardiac injury biomarkers in paediatric age: Are we there yet? Heart Fail Rev 2018; 21:771-781. [PMID: 27255332 DOI: 10.1007/s10741-016-9567-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The aim of this article is to evaluate the clinical utility of cardiac injury biomarkers in paediatric age. In December 2015, a literature search was performed (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included the following medical subject headings and text terms for the key words: "cardiac injury biomarkers", "creatine kinase-MB", "myoglobin", "troponin", "children", "neonate/s", "newborn/s", "infant/s" and echocardiography. In the paediatric population, troponins show a good correlation with the extent of myocardial damage following cardiac surgery and cardiotoxic medication and can be used as predictors of subsequent cardiac recovery and mortality. Elevation of cardiac injury biomarkers may also have diagnostic value in cases when cardiac contusion or pericarditis is suspected. Cardiac injury biomarkers are very sensitive markers for the detection of myocardial injury and have been studied in healthy newborns, after tocolysis, intrauterine growth restriction, respiratory distress and asphyxia. The proportion of newborns with elevated troponin was higher than that in ill infants, children, and adolescents and in healthy adults, suggesting that myocardial injury, although clinically occult, is common in this young age group. Results suggest that significant elevation of cord troponin is an excellent early predictor of severity of hypoxic-ischaemic encephalopathy and mortality in term infants. Cardiac biomarkers may also benefit centres without on-site echocardiography with evidence showing good correlation with echo-derived markers of myocardial function. Further studies are needed to better clarify the role of cardiac biomarkers in paediatric age and their correlation with echocardiographic parameters.
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Affiliation(s)
- Ana L Neves
- Department of Paediatric Cardiology, São João Hospital, Porto, Portugal. .,Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research Centre, Faculty of Medicine, University of Porto, Porto, Portugal. .,Department of Paediatrics, Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Tiago Henriques-Coelho
- Department of Paediatrics, Faculty of Medicine, University of Porto, Porto, Portugal.,Department of Paediatric Surgery, São João Hospital, Porto, Portugal
| | - Adelino Leite-Moreira
- Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research Centre, Faculty of Medicine, University of Porto, Porto, Portugal.,Department of Cardiothoracic Surgery, São João Hospital, Porto, Portugal
| | - José C Areias
- Department of Paediatric Cardiology, São João Hospital, Porto, Portugal.,Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research Centre, Faculty of Medicine, University of Porto, Porto, Portugal.,Department of Paediatrics, Faculty of Medicine, University of Porto, Porto, Portugal
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16
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Daigneault M, Harr KE, Dean KM, Bursian SJ. Reprint of: Assay Validation of the Cardiac Isoform of Troponin I in Double Crested Cormorant (Phalacrocorax auritus) Plasma for Diagnosis of Cardiac Damage. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2017; 146:129-133. [PMID: 28571623 DOI: 10.1016/j.ecoenv.2017.05.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 03/03/2017] [Accepted: 03/06/2017] [Indexed: 06/07/2023]
Abstract
Cardiac abnormalities, initially found in Deepwater Horizon weathered MC252 crude oil exposed Double Crested Cormorants (DCCOs) upon gross necropsy, were further investigated using echocardiography. Clinical and statistically significant changes including decreased ventricular myocardial contractility and arrhythmia were elucidated by echocardiography and interpreted by boarded cardiologists as potentially life threatening. The objective of this investigation was to initiate development of an antemortem, sensitive blood screening test for cardiac damage due to oil exposure of avian species. An assay for the cardiac isoform of troponin I (cTnI) which is known to be highly cross-reactive across mammalian species was chosen and analytically validated in DCCO. This is the first time this test has been analytically validated in avian species. All plasma samples from birds assessed as healthy had trace concentrations (<0.016ng/ml). The assays was precise and accurate revealing a coefficient of variation <3% and an R2>0.99. Diagnostic investigation revealed that the test appears to have diagnostic potential for the diagnosis of cardiomyocyte damage. Diagnostic sensitivity and specificity were 91% and 73% in this laboratory population. Due to an equivocal sample population in which health could not be proven, further investigation is needed to diagnostically validate troponin I in the assessment of oil exposure in DCCO.
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Affiliation(s)
- Melissa Daigneault
- Center for Bird and Exotic Animal Medicine. 11401 NE 195th Street. Bothell, WA 98011 USA
| | - Kendal E Harr
- Urika, LLC. 8712 53rd Place West, Mukilteo, WA 98275 USA.
| | - Karen M Dean
- Abt Associates, 1881 Ninth St., Suite 201, Boulder, CO 80302 USA
| | - Steven J Bursian
- Department of Animal Science, Michigan State University, East Lansing, MI 48824 USA
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17
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Daigneault M, Harr KE, Dean KM, Bursian SJ. Assay validation of the cardiac isoform of troponin I in double crested cormorant (Phalacrocorax auritus) plasma for diagnosis of cardiac damage. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2017; 141:52-56. [PMID: 28314141 DOI: 10.1016/j.ecoenv.2017.03.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 03/03/2017] [Accepted: 03/06/2017] [Indexed: 06/06/2023]
Abstract
Cardiac abnormalities, initially found in Deepwater Horizon weathered MC252 crude oil exposed Double Crested Cormorants (DCCOs) upon gross necropsy, were further investigated using echocardiography. Clinical and statistically significant changes including decreased ventricular myocardial contractility and arrhythmia were elucidated by echocardiography and interpreted by boarded cardiologists as potentially life threatening. The objective of this investigation was to initiate development of an antemortem, sensitive blood screening test for cardiac damage due to oil exposure of avian species. An assay for the cardiac isoform of troponin I (cTnI) which is known to be highly cross-reactive across mammalian species was chosen and analytically validated in DCCO. This is the first time this test has been analytically validated in avian species. All plasma samples from birds assessed as healthy had trace concentrations (<0.016ng/ml). The assays was precise and accurate revealing a coefficient of variation <3% and an R2>0.99. Diagnostic investigation revealed that the test appears to have diagnostic potential for the diagnosis of cardiomyocyte damage. Diagnostic sensitivity and specificity were 91% and 73% in this laboratory population. Due to an equivocal sample population in which health could not be proven, further investigation is needed to diagnostically validate troponin I in the assessment of oil exposure in DCCO.
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Affiliation(s)
- Melissa Daigneault
- Center for Bird and Exotic Animal Medicine. 11401 NE 195th Street. Bothell, WA 98011 USA
| | - Kendal E Harr
- Urika, LLC. 8712 53rd Place West, Mukilteo, WA 98275 USA.
| | - Karen M Dean
- Abt Associates, 1881 Ninth St., Suite 201, Boulder, CO 80302 USA
| | - Steven J Bursian
- Department of Animal Science, Michigan State University, East Lansing, MI 48824 USA
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18
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Lopez JR, Kolster J, Zhang R, Adams J. Increased constitutive nitric oxide production by whole body periodic acceleration ameliorates alterations in cardiomyocytes associated with utrophin/dystrophin deficiency. J Mol Cell Cardiol 2017. [PMID: 28623080 DOI: 10.1016/j.yjmcc.2017.06.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Duchenne Muscular Dystrophy (DMD) cardiomyopathy is a progressive lethal disease caused by the lack of the dystrophin protein in the heart. The most widely used animal model of DMD is the dystrophin-deficient mdx mouse; however, these mice exhibit a mild dystrophic phenotype with heart failure only late in life. In contrast, mice deficient for both dystrophin and utrophin (mdx/utrn-/-, or dKO) can be used to model severe DMD cardiomyopathy where pathophysiological indicators of heart failure are detectable by 8-10weeks of age. Nitric oxide (NO) is an important signaling molecule involved in vital functions of regulating rhythm, contractility, and microcirculation of the heart, and constitutive NO production affects the function of proteins involved in excitation-contraction coupling. In this study, we explored the efficacy of enhancing NO production as a therapeutic strategy for treating DMD cardiomyopathy using the dKO mouse model of DMD. Specifically, NO production was induced via whole body periodic acceleration (pGz), a novel non-pharmacologic intervention which enhances NO synthase (NOS) activity through sinusoidal motion of the body in a headward-footward direction, introducing pulsatile shear stress to the vascular endothelium and cardiomyocyte plasma membrane. Male dKO mice were randomized at 8weeks of age to receive daily pGz (480cpm, Gz±3.0m/s2, 1h/d) for 4weeks or no treatment, and a separate age-matched group of WT animals (pGz-treated and untreated) served as non-diseased controls. At the conclusion of the protocol, cardiomyocytes from untreated dKO animals had, respectively, 4.3-fold and 3.5-fold higher diastolic resting concentration of Ca2+ ([Ca2+]d) and Na+ ([Na+]d) compared to WT, while pGz treatment significantly reduced these levels. For dKO cardiomyocytes, pGz treatment also improved the depressed contractile function, decreased oxidative stress, blunted the elevation in calpain activity, and mitigated the abnormal increase in [Ca2+]d upon mechanical stress. These improvements culminated in a significant reduction in circulating cardiac troponin T (cTnT) and an extension of the median lifespan of dKO mice from 16 to 31weeks. Treatment with L-NAME (NOS inhibitor) significantly decreased overall lifespan and abolished the cardioprotective properties elicited by pGz. Our results provide evidence that enhancement of NO synthesis by pGz can ameliorate cellular dysfunction in dKO cardiomyocytes and may represent a novel therapeutic intervention in DMD cardiomyopathy patients.
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Affiliation(s)
- Jose R Lopez
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California at Davis, Davis, CA 95616, United States; Division of Neonatology, Mount Sinai Medical Center, Miami, FL 33140, United States.
| | - Juan Kolster
- Centro de Investigaciones Biomédicas, México, D.F., Mexico
| | - Rui Zhang
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California at Davis, Davis, CA 95616, United States
| | - Jose Adams
- Division of Neonatology, Mount Sinai Medical Center, Miami, FL 33140, United States
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19
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Kozinski M, Krintus M, Kubica J, Sypniewska G. High-sensitivity cardiac troponin assays: From improved analytical performance to enhanced risk stratification. Crit Rev Clin Lab Sci 2017; 54:143-172. [DOI: 10.1080/10408363.2017.1285268] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- Marek Kozinski
- Department of Principles of Clinical Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland
| | - Magdalena Krintus
- Department of Laboratory Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland
| | - Jacek Kubica
- Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland
| | - Grazyna Sypniewska
- Department of Laboratory Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland
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20
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Abstract
OBJECTIVES Assessment of whether admission plasma troponin I level is associated with mortality or requirement for vasoactive drugs in pediatric intensive care. DESIGN Retrospective cohort study. SETTING Single centre, tertiary referral general PICU, without a cardiac surgical program. PATIENTS Three hundred and nineteen patients 0-18 years old in two cohorts. Cohort 1 was admitted between January 2009 and September 2012 and the cohort 2 between April 2014 and April 2015. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Plasma troponin I was measured in patients in cohort 1 only if the attending physician ordered the test due to clinical concern regarding myocardial injury. The second cohort had plasma troponin I routinely measured at admission. The primary outcome was death during PICU admission, and the secondary outcome was maximum inotrope requirement during PICU stay, measured by Vasoactive Inotrope Score. Plasma troponin I was a discriminator for mortality in both cohorts (area under the receiver-operating characteristic curve of 0.73 and 0.86 in cohorts 1 and 2, respectively). In an adjusted analysis using Cox regression, accounting for Pediatric Index of Mortality 2 risk of mortality and age, elevated plasma troponin I was significantly associated with death in both cohorts (hazard ratio, 4.99; p = 0.033; hazard ratio, 10.5; p = 0.026 in cohorts 1 and 2, respectively). Elevated plasma troponin I was only associated with increased Vasoactive Inotrope Score following multivariate analysis in the cohort 2. CONCLUSIONS Detectable plasma troponin I at admission to PICU is independently associated with death. The utility of troponin I as a stratification biomarker requires further evaluation.
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21
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Wens SC, Schaaf GJ, Michels M, Kruijshaar ME, van Gestel TJ, in ‘t Groen S, Pijnenburg J, Dekkers DH, Demmers JA, Verdijk LB, Brusse E, van Schaik RH, van der Ploeg AT, van Doorn PA, Pijnappel WP. Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease. ACTA ACUST UNITED AC 2016; 9:6-13. [DOI: 10.1161/circgenetics.115.001322] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 01/14/2016] [Indexed: 01/19/2023]
Abstract
Background—
Elevated plasma cardiac troponin T (cTnT) levels in patients with neuromuscular disorders may erroneously lead to the diagnosis of acute myocardial infarction or myocardial injury.
Methods and Results—
In 122 patients with Pompe disease, the relationship between cTnT, cardiac troponin I, creatine kinase (CK), CK-myocardial band levels, and skeletal muscle damage was assessed. ECG and echocardiography were used to evaluate possible cardiac disease. Patients were divided into classic infantile, childhood-onset, and adult-onset patients. cTnT levels were elevated in 82% of patients (median 27 ng/L, normal values <14 ng/L). Cardiac troponin I levels were normal in all patients, whereas CK-myocardial band levels were increased in 59% of patients. cTnT levels correlated with CK levels in all 3 subgroups (
P
<0.001). None of the abnormal ECGs recorded in 21 patients were indicative of acute myocardial infarction, and there were no differences in cTnT levels between patients with and without (n=90) abnormalities on ECG (median 28 ng/L in both groups). The median left ventricular mass index measured with echocardiography was normal in all the 3 subgroups. cTnT mRNA expression in skeletal muscle was not detectable in controls but was strongly induced in patients with Pompe disease. cTnT protein was identified by mass spectrometry in patient-derived skeletal muscle tissue.
Conclusions—
Elevated plasma cTnT levels in patients with Pompe disease are associated with skeletal muscle damage, rather than acute myocardial injury. Increased cTnT levels in Pompe disease and likely other neuromuscular disorders should be interpreted with caution to avoid unnecessary cardiac interventions.
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Affiliation(s)
- Stephan C.A. Wens
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Gerben J. Schaaf
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Michelle Michels
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Michelle E. Kruijshaar
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Tom J.M. van Gestel
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Stijn in ‘t Groen
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Joon Pijnenburg
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Dick H.W. Dekkers
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Jeroen A.A. Demmers
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Lex B. Verdijk
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Esther Brusse
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Ron H.N. van Schaik
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Ans T. van der Ploeg
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - Pieter A. van Doorn
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
| | - W.W.M. Pim Pijnappel
- From the Department of Neurology (S.C.A.W., E.B., P.A.v.D.), Center for Lysosomal and Metabolic Diseases (S.C.A.W., G.J.S., M.E.K., T.J.M.v.G., S.G., J.P., E.B., A.T.v.d.P., P.A.v.D., W.W.M.P.P.), Molecular Stem Cell Biology, Department of Clinical Genetics (G.J.S., T.J.M.v.G., S.G., J.P., W.W.M.P.P.), Department of Cardiology (M.M.), Department of Clinical Chemistry (R.H.N.v.S.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Division of Metabolic Diseases and Genetics,
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Karapinar T, Eroksuz Y, Hayirli A, Beytut E, Kaynar O, Baydar E, Sozdutmaz I, Isidan H. The diagnostic value of two commercially available human cTnI assays in goat kids with myocarditis. Vet Clin Pathol 2016; 45:164-71. [PMID: 26802431 DOI: 10.1111/vcp.12328] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Cardiac troponin I (cTnI) is a peripheral blood marker for myocardial damage. Because of the unavailability of goat-specific cTnI assays human cTnI assays may be validated for detection of myocarditis in goat kids. OBJECTIVES The purpose of the study was to evaluate 2 commercially available human cTnI assays in goat kids with myocardial damage, and to determine the cTnI expression in cardiac muscle. MATERIALS AND METHODS Plasma cTnI concentrations were measured in healthy goat kids (n = 7) and goat kids with myocardial damage (n = 8) using the Beckman Coulter Access Accu TnI and the Biomérieux Vidas Ultra. The results were correlated with gross necropsy and histopathologic findings, and cTnI immunhistochemistry in cardiac tissue. RESULTS Macro- and microscopic findings confirmed myocardial damage in the myocarditis group. Mean plasma cTnI concentration was significantly higher in the myocarditis group than in the healthy control group (104.82 vs 0.02 ng/mL). The overall mean plasma cTnI concentration measured by Biomérieux Vidas Ultra (61.75 ng/mL, 95% CI: 19.55-103.95) was comparable to the mean measured by Beckman Coulter Access Accu TnI (50.08 ng/mL, 95% CI: 24.11-76.06), and cTnI concentrations measured by these assays were highly correlated (r = .977) with a -6.2% bias. Both assays were precise and accurate. CONCLUSION The human-specific Beckman Coulter Access Accu TnI and the Biomérieux Vidas Ultra can be used for diagnostic confirmation of myocardial damage in caprine medicine.
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Affiliation(s)
- Tolga Karapinar
- Department of Internal Medicine, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | - Yesari Eroksuz
- Department of Pathology, Veterinary Faculty, Firat University, Elazig, Turkey
| | - Armagan Hayirli
- Department of Animal Nutrition and Nutritional Disorders, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey
| | - Enver Beytut
- Department of Pathology, Veterinary Faculty, Kafkas University, Kars, Turkey
| | - Ozgur Kaynar
- Department of Biochemistry, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey
| | - Ersoy Baydar
- Department of Internal Medicine, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | - Ibrahim Sozdutmaz
- Department of Virology, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Turkey
| | - Hakan Isidan
- Department of Virology, Faculty of Veterinary Medicine, Cumhuriyet University, Sivas, Turkey
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Hong EJ, Jeung EB. Assessment of Developmental Toxicants using Human Embryonic Stem Cells. Toxicol Res 2014; 29:221-7. [PMID: 24578791 PMCID: PMC3936173 DOI: 10.5487/tr.2013.29.4.221] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2013] [Revised: 12/05/2013] [Accepted: 12/12/2013] [Indexed: 01/16/2023] Open
Abstract
Embryonic stem (ES) cells have potential for use in evaluation of developmental toxicity because they are generated in large numbers and differentiate into three germ layers following formation of embryoid bodies (EBs). In earlier study, embryonic stem cell test (EST) was established for assessment of the embryotoxic potential of compounds. Using EBs indicating the onset of differentiation of mouse ES cells, many toxicologists have refined the developmental toxicity of a variety of compounds. However, due to some limitation of the EST method resulting from species-specific differences between humans and mouse, it is an incomplete approach. In this regard, we examined the effects of several developmental toxic chemicals on formation of EBs using human ES cells. Although human ES cells are fastidious in culture and differentiation, we concluded that the relevancy of our experimental method is more accurate than that of EST using mouse ES cells. These types of studies could extend our understanding of how human ES cells could be used for monitoring developmental toxicity and its relevance in relation to its differentiation progress. In addition, this concept will be used as a model system for screening for developmental toxicity of various chemicals. This article might update new information about the usage of embryonic stem cells in the context of their possible ability in the toxicological fields.
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Affiliation(s)
- Eui-Ju Hong
- Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
| | - Eui-Bae Jeung
- Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea
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24
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Shahzadi A, Sonmez I, Allahverdi O, Onal B, Kandaz C, Ozyazgan SO, Akkan AG, Yazici Z. Cardiac Troponin-I (cTnI) a Biomarker of Cardiac Injuries Induced by Doxorubicin Alone and in Combination with Ciprofloxacin, Following Acute and Chronic Dose Protocol in Sprague Dawley Rats. INT J PHARMACOL 2014. [DOI: 10.3923/ijp.2014.258.266] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Cooper DL, Murrell DE, Conder CM, Palau VE, Campbell GE, Lynch SP, Denham JW, Hanley AV, Bullins KW, Panus PC, Singh K, Harirforoosh S. Exacerbation of celecoxib-induced renal injury by concomitant administration of misoprostol in rats. PLoS One 2014; 9:e89087. [PMID: 24586517 PMCID: PMC3931696 DOI: 10.1371/journal.pone.0089087] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Accepted: 01/15/2014] [Indexed: 01/01/2023] Open
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often utilized to alleviate NSAID-related gastrointestinal side effects. This study examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the effects of these drugs on cardiovascular parameters were evaluated. Four randomized rat groups were orally gavaged for 9 days, two groups receiving vehicle and two groups receiving misoprostol (100 µg/kg) twice daily. Celecoxib (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol group from days 3 to 9. Urine and blood samples were collected and blood pressure parameters were measured during the study period. Hearts and kidneys were harvested on final day. Day 2 urinary electrolyte samples revealed significant reductions in sodium excretion in misoprostol (0.12 ± 0.05 µmol/min/100 g) and misoprostol+celecoxib groups (0.07 ± 0.02 µmol/min/100 g). At day 3, all treatment groups showed significantly reduced sodium excretion. Potassium excretion diminished significantly in vehicle+celecoxib and misoprostol+celecoxib groups from day 3 onward. Urinary kidney injury molecule-1 levels were significantly increased in vehicle+celecoxib (0.65 ± 0.02 vs. 0.35 ± 0.07 ng/mL, p = 0.0002) and misoprostol+celecoxib (0.61 ± 0.06 vs. 0.37 ± 0.06 ng/mL, p = 0.0015) groups when compared to baseline; while plasma levels of cardiac troponin I increased significantly in vehicle+celecoxib (p = 0.0040) and misoprostol+misoprostol (p = 0.0078) groups when compared to vehicle+vehicle. Blood pressure parameters increased significantly in all misoprostol treated groups. Significant elevation in diastolic (p = 0.0071) and mean blood pressure (p = 0.0153) was noted in misoprostol+celecoxib compared to vehicle+celecoxib. All treatments produced significant tubular dilatation/necrosis compared to control. No significant myocardial changes were noticed; however, three animals presented with pericarditis. Kidney, heart, and plasma celecoxib levels revealed no significant change between vehicle+celecoxib and misoprostol+celecoxib. Concomitant misoprostol administration did not prevent celecoxib renal toxicity, and instead exacerbated renal side effects. Misoprostol did not alter plasma or tissue celecoxib concentrations suggesting no pharmacokinetic interaction between celecoxib and misoprostol.
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Affiliation(s)
- Dustin L. Cooper
- Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Derek E. Murrell
- Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Christopher M. Conder
- Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Victoria E. Palau
- Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Grace E. Campbell
- Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Shaun P. Lynch
- Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - James W. Denham
- Department of Pathology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Angela V. Hanley
- Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Kenny W. Bullins
- Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Peter C. Panus
- Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Krishna Singh
- Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, United States of America
| | - Sam Harirforoosh
- Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, Tennessee, United States of America
- * E-mail:
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O'Brien PJ. Blood cardiac troponin in toxic myocardial injury: archetype of a translational safety biomarker. Expert Rev Mol Diagn 2014; 6:685-702. [PMID: 17009904 DOI: 10.1586/14737159.6.5.685] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
A translational safety biomarker for toxic myocardial injury is needed in drug discovery and development. This need reflects the increasing recognition of occurrence of cardiotoxicities, prior lack of preclinical blood biomarkers for toxic cardiac injury, introduction of troponin as a biomarker, and regulatory and industry drivers. Cardiac troponin is considered the gold-standard biomarker in humans for cardiac injury due to ischemic injury and drug toxicity. It has been demonstrated to correlate highly with histopathological extent of injury, degree of impairment of cardiac function, and prognosis. Numerous studies have now clearly demonstrated that both cardiac troponin T and cardiac troponin I are sensitive and specific biomarkers of cardiac injury in laboratory animals. Their use is highly recommended for incorporation into preclinical drug-safety studies, especially whenever there is any history of cardiac effect in prior studies with a compound of the same or similar chemical or pharmacological class. The main caveats with respect to cross-species use of specific cardiac troponin assays are the need for species-specific validation, definition of cut-offs based on relevant assessments of imprecision and reference ranges or concurrent controls, and knowledge of the species-dependent kinetics of release into, and clearance from, the blood. Future development of high-sensitivity assays should determine whether minimal increases below a threshold concentration of troponin might reflect reversible myocardial effects.
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Affiliation(s)
- Peter James O'Brien
- Sandwich Laboratories, Pfizer Global Research and Development, Sandwich, Kent, CT13 9NJ, UK.
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Chon H, Lee S, Yoon SY, Lee EK, Chang SI, Choo J. SERS-based competitive immunoassay of troponin I and CK-MB markers for early diagnosis of acute myocardial infarction. Chem Commun (Camb) 2014; 50:1058-60. [DOI: 10.1039/c3cc47850e] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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Karimian N, Vagin M, Zavar MHA, Chamsaz M, Turner AP, Tiwari A. An ultrasensitive molecularly-imprinted human cardiac troponin sensor. Biosens Bioelectron 2013; 50:492-8. [DOI: 10.1016/j.bios.2013.07.013] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Accepted: 07/06/2013] [Indexed: 10/26/2022]
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Parwani AS, Boldt LH, Huemer M, Wutzler A, Blaschke D, Rolf S, Möckel M, Haverkamp W. Atrial fibrillation-induced cardiac troponin I release. Int J Cardiol 2013; 168:2734-7. [PMID: 23623668 DOI: 10.1016/j.ijcard.2013.03.087] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2010] [Revised: 02/07/2013] [Accepted: 03/23/2013] [Indexed: 11/25/2022]
Abstract
BACKGROUND Cardiac troponin I (cTnI) is highly specific for myocardial damage and for the diagnosis of acute coronary syndrome. We investigated cTnI utility and predictive value in patients with atrial fibrillation (AF) in the acute setting. METHOD We studied 354 consecutive patients with the primary diagnosis of AF and clinical symptoms suggestive of myocardial ischemia presenting to our emergency department. cTnI was obtained on presentation. Patients with ST-segment elevation myocardial infarction were excluded. Coronary angiography was performed in 100 patients. RESULTS cTnI was elevated (>0.09 μg/L) in 51 of 354 (15%) patients. The mean cTnI in these patients was 0.37 μg/L (0.09-3.14). In 23 of 100 patients undergoing coronary angiography, cTnI was elevated. Only 6 of these 23 patients (26%) had significant stenosis. In 77 of 100 patients undergoing coronary angiography, cTnI was normal, revealing significant stenosis in 25 patients (33%). The positive predictive value of elevated cTnI for a coronary intervention was 26% and the negative predictive value was 68%. Using multivariate logistic regression, we found that heart rate on presentation, the presence of angina pectoris, left ventricular ejection fraction, serum creatinine, and hemoglobin independently predicted elevated cTnI level. CONCLUSION These data are the first to show that AF in the acute setting is frequently associated with cTnI elevations. AF patients with high heart rate and/or angina pectoris often show false elevated cTnI levels. These findings are relevant for clinicians evaluating patients with acute AF and myocardial ischemia symptoms. Appropriate clinical guidelines must be established that also consider AF-related elevations in cTnI.
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Sangha GS, Pepelassis D, Buffo-Sequeira I, Seabrook JA, Fraser DD. Serum troponin-I as an indicator of clinically significant myocardial injury in paediatric trauma patients. Injury 2012; 43:2046-50. [PMID: 22119453 DOI: 10.1016/j.injury.2011.10.034] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Revised: 10/05/2011] [Accepted: 10/28/2011] [Indexed: 02/02/2023]
Abstract
Myocardial injury is a cause of mortality in paediatric trauma, but it is often difficult to diagnose. The objectives of this pilot study were to (1) determine the prevalence of elevated cardiac troponin I (TnI) in paediatric trauma patients and (2) to determine whether elevated TnI correlates with clinically significant myocardial injury, defined as abnormalities on echocardiogram (ECHO) and/or electrocardiograms (ECG). To this end, we investigated a convenient sample size of 59 paediatric trauma patients with an Injury Severity Score (ISS)>12. TnI and creatine kinase-MB (CK-MB) were measured on admission, at then at regular intervals until TnI had normalized. Patients with elevated TnI levels had an ECHO performed within 24h of admission and underwent daily ECGs until TnI normalized. Elevated serum TnI was found in n=16/59 (27%; 95% CI: 18-40%) patients and was associated with elevated CK-MB in all cases. Abnormal ECHOs were seen in 4/16 patients with elevated TnI, but peak TnI values did not correlate with abnormalities on ECHO (p=0.23). Only 1 patient had a clinically significant, albeit mild, decrease in cardiac function. All ECGs were normal. Patients with elevated TnI were more likely to be intubated (p=0.04), to have higher Injury Severity Scores (p=0.02), required more resuscitation fluid (p=0.001), and to have thoracic injuries (p<0.001). Our data indicates that the prevalence of elevated TnI in paediatric trauma patients is 27%; and whilst elevated TnI reflects overall trauma severity, it is frequently elevated without a clinically significance myocardial injury. Hence, large scale studies are required to determine if an elevated threshold TnI value can be identified to accurately diagnose severe myocardial injury in paediatric trauma.
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Affiliation(s)
- Gurinder S Sangha
- Emergency Medicine and Paediatrics, University of Western Ontario, London, ON, Canada
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Karapinar T, Eroksuz Y, Beytut E, Sozdutmaz I, Eroksuz H, Dabak M. Increased plasma cardiac troponin I concentration in lambs with myocarditis. Vet Clin Pathol 2012; 41:375-81. [PMID: 22747688 DOI: 10.1111/j.1939-165x.2012.00448.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Cardiac troponin I (cTnI) is a blood biomarker of myocardial injury. A human cTnI assay may be useful for measuring cTnI concentrations in lambs with naturally occurring myocarditis. OBJECTIVE The aims of this study were to evaluate the utility of a commercially available human chemiluminescent microparticle cTnI immunoassay for measuring plasma cTnI concentrations in lambs with naturally occurring myocarditis from infection with foot and mouth disease virus (FMDV), and to determine cTnI expression in cardiac muscle of affected lambs. METHODS Ten lambs with myocarditis and 10 clinically healthy lambs (control group) were included. Clinical signs, gross and histologic necropsy findings, and immunoreactivity for cTnI in cardiac tissue were evaluated. Plasma cTnI concentration was determined using the commercial human immunoassay system. RESULTS All lambs with myocarditis died within 1 day of clinical signs. Infection with FMDV was confirmed by PCR analysis. Gross cardiac lesions were evident and histologic examination revealed myocarditis. Immunoreactivity for cTnI was absent in cardiac myocytes that were degenerative or necrotic, but was strong in cardiac myocytes from unaffected areas of the myocardium and in all cardiac myocytes of healthy lambs. The geometric mean plasma concentrations of cTnI for lambs in the myocarditis and control groups were 146.78 μg/L (95% confidence interval [CI], 61.90-348.06) and 0.013 μg/L (95% CI, 0.010-0.017), respectively (t-value 19.27; P < .0001). CONCLUSIONS A commercial human cTnI assay may be used to detect plasma cTnI concentrations in sheep, and cTnI may be used as a blood-based biomarker of myocarditis in this species.
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Affiliation(s)
- Tolga Karapinar
- Department of Internal Medicine, Firat University, Hastaliklari Anabilim Dali, Elazig 23119, Turkey.
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Bealer SL, Little JG, Metcalf CS, Brewster AL, Anderson AE. Autonomic and cellular mechanisms mediating detrimental cardiac effects of status epilepticus. Epilepsy Res 2010; 91:66-73. [PMID: 20650612 PMCID: PMC3212408 DOI: 10.1016/j.eplepsyres.2010.06.013] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2010] [Revised: 06/09/2010] [Accepted: 06/23/2010] [Indexed: 11/22/2022]
Abstract
Prolonged seizure activity (status epilepticus; SE) can result in increased susceptibility to lethal ventricular arrhythmias for an extended period of time following seizure termination. SE is accompanied by acute, intense activation of the sympathetic nervous system (SymNS) and results in myocyte myofilament damage, arrhythmogenic alterations in cardiac electrical activity, and increased susceptibility to ventricular arrhythmias. However, the mechanisms mediating the changes in cardiac function, and the specific arrhythmogenic substrate produced during SE are unknown. To determine if detrimental cardiac effects of SE are mediated by SymNS stimulation of the heart, we examined the effects of B-adrenergic blockade (atenolol) during seizure activity on blood pressure, heart rate, myocyte myofilament injury (cardiac troponin I, cTnI), electrocardiographic activity, and susceptibility to arrhythmias. Furthermore, we determined if SE was associated with altered expression of the Kv4.x potassium channels, which are critical for action potential repolarization and thereby contribute significantly to normal cardiac electrical activity. Lithium-pilocarpine induced SE was associated with acute tachycardia, hypertension, and cardiomyocyte damage. Arrhythmogenic alterations in cardiac electrical activity accompanied by increased susceptibility to experimentally induced arrhythmias were evident during the first 2 weeks following SE. Both were prevented by atenolol treatment during seizures. Furthermore, one and two weeks after SE, myocyte ion channel remodeling, characterized by a decreased expression of cardiac Kv4.2 potassium channels, was evident. These data suggest that the cardiac effects of prolonged and intense SymNS activation during SE induce myofilament damage and downregulation of Kv4.2 channels, which alter cardiac electrical activity and increase susceptibility to lethal arrhythmias.
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Affiliation(s)
- Steven L Bealer
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84121, United States.
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Dual-cardiac marker capillary waveguide fluoroimmunosensor based on tyramide signal amplification. Anal Bioanal Chem 2009; 396:1187-96. [DOI: 10.1007/s00216-009-3278-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2009] [Revised: 10/29/2009] [Accepted: 10/31/2009] [Indexed: 10/20/2022]
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Metcalf CS, Poelzing S, Little JG, Bealer SL. Status epilepticus induces cardiac myofilament damage and increased susceptibility to arrhythmias in rats. Am J Physiol Heart Circ Physiol 2009; 297:H2120-7. [PMID: 19820194 DOI: 10.1152/ajpheart.00724.2009] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Status epilepticus (SE) is a seizure or series of seizures that persist for >30 min and often results in mortality. Death rarely occurs during or immediately following seizure activity, but usually within 30 days. Although ventricular arrhythmias have been implicated in SE-related mortality, the effects of this prolonged seizure activity on the cardiac function and susceptibility to arrhythmias have not been directly investigated. We evaluated myocardial damage, alterations in cardiac electrical activity, and susceptibility to experimentally induced arrhythmias produced by SE in rats. SE resulted in seizure-related increases in blood pressure, heart rate, and the first derivative of pressure, as well as modest, diffuse myocyte damage assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. Ten to twelve days following seizures, electrocardiographic recordings showed arrhythmogenic alterations in cardiac electrical activity, denoted by prolonged QT interval corrected for heart rate and QT dispersion. Finally, SE increased susceptibility to experimentally induced (intravenous aconitine) cardiac arrhythmias. These data suggest that SE produces tachycardic ischemia following the activation of the sympathetic nervous system, resulting in cardiac myofilament damage, arrhythmogenic alterations in cardiac electrical activity, and increased susceptibility to ventricular arrhythmias.
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Affiliation(s)
- Cameron S Metcalf
- Department of Pharmacology and Toxicology, University of Utah, 30 S. 2000 East Rm. 201, Salt Lake City, UT 84112, USA
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Development of lateral flow immunoassay system based on superparamagnetic nanobeads as labels for rapid quantitative detection of cardiac troponin I. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2009. [DOI: 10.1016/j.msec.2009.01.009] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Mastella AK, Moresco RN, da Silva DB, Becker AM, Duarte MMMF, Giovelli LL, da Silva SH, Rossato L, Moretto MB, da Silva JEP. Evaluation of ischemia-modified albumin in myocardial infarction and prostatic diseases. Biomed Pharmacother 2009; 63:762-6. [PMID: 19375269 DOI: 10.1016/j.biopha.2008.12.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2008] [Revised: 11/24/2008] [Accepted: 12/23/2008] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Ischemia-modified albumin (IMA) has been shown to be a rapidly rising and sensitive biochemical marker for the diagnosis of myocardial ischemia. In this study, we evaluated the levels of IMA in myocardial infarction and prostate diseases, as well as the influence of HDL cholesterol levels on C-reactive protein (CRP) and IMA levels. METHODS A total of 27 patients with myocardial infarction (MI), 102 patients with benign prostatic hyperplasia (BPH), 84 patients with prostate cancer (PCA), and 21 healthy subjects were enrolled in this study. IMA levels were measured in whole studied patients. Cardiac troponin I (cTnI), cholesterol, HDL cholesterol, and CRP were measured in MI and control groups. RESULTS IMA values were significantly higher in patients with MI (0.5215+/-0.0241 ABSU) and BPH (0.4150+/-0.0156 ABSU) in comparison to control subjects (0.3381+/-0.0194 ABSU). IMA and CRP were higher in MI group, especially in patients with HDL cholesterol levels lower than 38 mg/dL. The ability of IMA to discriminate myocardial infarction was higher than CRP. Significant correlations between CRP and HDL, CRP and IMA, and HDL and IMA were reported. CONCLUSIONS IMA and CRP increase in myocardial damage, and the decrease of HDL cholesterol appears to enhance the inflammatory response. IMA also increase in benign prostate hyperplasia and this finding suggests that the diagnosis of prostate diseases must be considered on evaluation of IMA as a marker of cardiac ischemia.
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Affiliation(s)
- Aline K Mastella
- Department of Clinical and Toxicological Analysis, Centre of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
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Dutra RF, Mendes RK, Lins da Silva V, Kubota LT. Surface plasmon resonance immunosensor for human cardiac troponin T based on self-assembled monolayer. J Pharm Biomed Anal 2007; 43:1744-50. [PMID: 17254730 DOI: 10.1016/j.jpba.2006.12.013] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2006] [Revised: 12/11/2006] [Accepted: 12/13/2006] [Indexed: 11/19/2022]
Abstract
The cardiac troponin T (cTnT) is specific biomarker important for trials of acute myocardial infarctions (AMI). In this paper, a SPR sensor in real time to detect the biomarker was developed on a commercially available surface plasmon resonance AUTOLAB SPIRIT. The cTnT receptor molecule was covalently immobilized on a gold substrate via a self-assembled monolayer (SAM) of thiols by using cysteamine-coupling chemistry. This biosensor presented a linear response range for cTnT between 0.05 and 4.5 ng/mL (r=0.997, p<<0.01) with a good reproducibility (CV=4.4%). The effect of the cysteamine (CYS) concentrations on the SAM coated gold sensor was studied as a function of the amount of the immobilized cTnT monoclonal antibodies. Analysis using serum samples undiluted was carried out at room temperature showing a well agreement with the ECLIA methods and the sensor surface could be regenerated by using a solution of 1% (w/v) sodium dodecyl sulphate (SDS) without losing the sensor immunoreactivity. These studies open new perspectives of using SAM to develop regenerable immunosensor with a good reproducibility allowing its use in the clinical applications.
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Affiliation(s)
- Rosa Fireman Dutra
- Departamento de Patologia, Instituto de Ciências Biológicas, Universidade de Pernambuco, Rua Arnóbio Marques, 310, Santo Amaro, 50100-130 Recife, PE, Brazil
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Dutra RF, Kubota LT. An SPR immunosensor for human cardiac troponin T using specific binding avidin to biotin at carboxymethyldextran-modified gold chip. Clin Chim Acta 2007; 376:114-20. [PMID: 16989795 DOI: 10.1016/j.cca.2006.07.029] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2006] [Revised: 07/24/2006] [Accepted: 07/31/2006] [Indexed: 11/22/2022]
Abstract
BACKGROUND The cardiac troponin T (TnT) is a cardiospecific, highly sensitive marker for myocardial damage and is immediately released to bloodstream during the acute myocardial infarction (AMI). Surface plasmon resonance (SPR) immunosensor was developed for the quick detection of human cTnT in real time. METHODS An SPR sensor streptavidin terminated self-assembled monolayer, which was used to binding biotinylated anti troponin T monoclonal antibodies, was developed. RESULTS The cTnT was determined from successive injections with a linear range from 0.03 up to 6.5 ng/ml. The detection limit was 0.01 ng/ml corresponding to a resonant angle change of 1.28 millidegrees. The system presented a good repeatability with 3.4% of variation between run after regeneration of the coated surface with a solution of 1% SDS. The effects of blocking of non-specific adsorption using different solutions were studied. It was possible to measure the cTnT without dilution of the human serum with good specificity and reproducibility. CONCLUSION This sensor is practical and offer quick response in interval of 800 s.
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Affiliation(s)
- Rosa Fireman Dutra
- Departamento de Patologia, Instituto de Ciências Biológicas, Universidade de Pernambuco, Recife, Brasil, Rua Arnóbio Marques, 310, Santo Amaro, 50100-130. Recife, PE , Brazil
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Guerin V, Ayed SB, Varnous S, Golmard JL, Leprince P, Beaudeux JL, Gandjbakhch I, Bernard M. Release of Brain Natriuretic-Related Peptides (BNP, NT-proBNP) and Cardiac Troponins (cTnT, cTnI) in On-pump and Off-pump Coronary Artery Bypass Surgery. Surg Today 2006; 36:783-9. [PMID: 16937281 DOI: 10.1007/s00595-006-3247-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2005] [Accepted: 05/16/2006] [Indexed: 11/28/2022]
Abstract
BACKGROUND We studied the kinetic release of cardiac troponins (cTnI and cTnT) and B-type natriuretic peptides (BNP and NT-proBNP) in patients undergoing off-pump or on-pump coronary artery bypass surgery. METHODS Twenty-five consecutive patients were prospectively enrolled. The patients were divided into three groups: beating heart (I), and cardiopulmonary bypass (CPB) with warm (II) or cold cardioplegia (III). Plasma samples were obtained before anesthesia induction until the sixth day after surgery. RESULTS AND CONCLUSIONS The data were analyzed first for off-pump versus the CPB procedures and second for warm versus cold cardioplegia. The plasma troponin releases appeared to be significantly higher in the CPB groups in comparison to the beating heart group (P < 0.001 and P < 0.002 for cTnI and cTnT peak values, respectively). The peak of the B-type natriuretic peptide release appeared to be more delayed in the groups undergoing CPB than in the beating heart group (day 6 versus days 2 and 4 for NT-proBNP and BNP, respectively). Taken together, our results indicated that the new generation of cTnT assays seemed to be more sensitive than the cTnI assays for the diagnosis of myocardium injury. A lower increase in the cTnT values in the warm cardioplegic group indicated less damage of the myocardium than with cold cardioplegia. Our data also confirm better preservation of the myocardium with off-pump cardiac surgery than with CPB.
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Affiliation(s)
- Valérie Guerin
- Department of Cardiothoracic Surgery, CHU Pitié-Salpêtrière, Pitié-Salpêtrière Hospital, AP-HP, 47-83 Boulevard de l'Hôpital, 75651 Paris, Cedex 13, France
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Liang JC, Chen HR, Chiu CC, Liou SF, Chen IJ, Yeh JL. Protective effect of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker, on myocardial apoptosis in ischemia-reperfusion injury. Life Sci 2006; 79:1248-56. [PMID: 16647091 DOI: 10.1016/j.lfs.2006.03.033] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2005] [Revised: 02/24/2006] [Accepted: 03/27/2006] [Indexed: 11/17/2022]
Abstract
The effects of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker with alpha-/beta-adrenoceptor blocking activities, on myocardial infarct size, apoptosis and necrosis in the rat after myocardial ischemia/reperfusion (45 min/120 min) were investigated. Ten minutes prior to left coronary artery occlusion, rats were treated with vehicle or labedipinedilol-A (0.25 or 0.5 mg/kg, i.v.). In the vehicle group, myocardial ischemia-reperfusion induced creatine kinase (CK) release and caused cardiomyocyte apoptosis, as evidenced by DNA ladder formation and terminal dUTP deoxynucleotidyltransferase nick end-labeling (TUNEL) staining. Treatment with labedipinedilol-A (0.25 or 0.5 mg/kg) reduced infarct size significantly compared to vehicle group (18.75+/-0.65% and 8.27+/-0.29% vs. 41.72+/-0.73%, P<0.01). Labedipinedilol-A also reduced the CK, CK-MB, lactate dehydrogenase (LDH) and troponin T levels in blood. In addition, labedipinedilol-A (0.5 mg/kg) significantly decreased TUNEL positive cells from 19.21+/-0.52% to 9.73+/-0.81% (P<0.01), which is consistent with absence of DNA ladders in the labedipinedilol-A group. Moreover, labedipinedilol-A pretreatment also decreased calcium content in ischemic-reperfused myocardial tissue. In conclusion, these results demonstrate that labedipindielol-A, through reduction of calcium overload and apoptosis, exerts anti-infarct effect during myocardial ischemia-reperfusion and would be useful clinically in the prevention of acute myocardial infarction.
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Affiliation(s)
- Jhy-Chong Liang
- Department of Early Childhood Care and Education, Chin Min Institute of Technology, Miaoli County, Taiwan
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Charpentier J, Cariou A. Biological evaluation of perioperative cardiac stress: a two-way approach. Crit Care Med 2006; 34:1259-60. [PMID: 16550081 DOI: 10.1097/01.ccm.0000208108.32815.a2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Moresco RN, Vargas LCR, Júnior RH, da Rocha Silla LM. Lack of association between cardiac troponin T and D-dimer in the evaluation of myocardial damage. J Clin Lab Anal 2006; 19:282-4. [PMID: 16302207 PMCID: PMC6808126 DOI: 10.1002/jcla.20082] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Acute myocardial infarction (AMI) disrupts cardiac cell membranes, releasing intracellular cardiac proteins into the vascular system. Some of these proteins, including the cardiac troponin subunits T and I, have proven useful for diagnosing myocardial damage. Intracoronary thrombosis plays a key role in the pathogenesis of AMI, and the formation of an occlusive thrombus usually precedes the development of myocardial damage. To evaluate whether there is an association between the size of intracoronary thrombosis and myocardial damage, we analyzed D-dimer and cTnT levels in blood samples from patients suspected to have myocardial damage. We investigated 102 patients who were admitted to emergency service for suspected myocardial damage. D-dimer was assessed with the use of the immunoassay Liatest D-dimer, and cTnT levels were measured with an electrochemiluminescence immunoassay (Troponin T STAT). D-dimer levels were lower in patients with cTnT < 0.01 than in patients presenting cTnT > 0.01 ng/mL. We investigated the relationship between D-dimer and cTnT levels in the patients with cTnT > 0.01 ng/mL (0.40 +/- 0.10 ng/mL), and no significant agreement (r = 0.20, P > 0.05) was observed. The levels of D-dimer were not associated with the levels of cTnT in patients with cTnT > 0.01 ng/mL.
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Affiliation(s)
- Rafael Noal Moresco
- Serviço de Hematologia Clínica e Transplante de Medula Ossea, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Brazil.
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Pruvot S, Galidie G, Bergmann JF, Mahé I. La troponine et les autres marqueurs de souffrance myocardique, quelle signification en médecine interne ? Rev Med Interne 2006; 27:215-26. [PMID: 16337716 DOI: 10.1016/j.revmed.2005.09.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2005] [Accepted: 09/28/2005] [Indexed: 10/25/2022]
Abstract
PURPOSE Troponin is now the gold standard for the diagnosis of myocardial infarction. Aiming at improving the management of a patient suspect of an acute coronary syndrome, this article will point the interpretation of troponin dosages according to the clinical presentation and concomitant diseases. ACTUALITIES First, the interest of troponin dosage as compared with other markers of myocardial ischemia will be underlined. Then, the literature available about troponin in cardiovascular diseases but also in extracardiac diseases will be analysed. Finally, the difficulties of assay will be discussed. PERSPECTIVES The availability of a sensitive and specific marker such as troponin is definitively a progress in the management of patients with an acute coronary syndromes. But it remains a biological contribution to the global management of the patient. It is important to know the causes susceptible to increase the levels of troponin to avoid a wrong interpretation of the dosage, leading to diagnostic but also therapeutic mistakes.
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Affiliation(s)
- S Pruvot
- Service de Médecine A, Hôpital Lariboisière, Paris, France
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Modesti PA, Simonetti I, Olivo G. Perioperative myocardial infarction in non-cardiac surgery. Pathophysiology and clinical implications. Intern Emerg Med 2006; 1:177-86. [PMID: 17120463 DOI: 10.1007/bf02934735] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Advances in surgical and anaesthetic techniques and an aging patient population have resulted in more complex procedures being performed in greater numbers of aged subjects and in patients with a high likelihood of significant cardiovascular disease. Nearly one fourth of non-cardiac surgical procedures (major intra-abdominal, thoracic, vascular, and orthopaedic procedures) performed in persons older than 65 years have been found to be associated with significant perioperative cardiovascular morbidity and mortality. During previous years the main attempt was to define strategies to accurately estimate perioperative cardiovascular risk based either on the characteristics of surgery and on patient characteristics. More recently preventive medical strategies have been proposed. Therefore, the physician has to be aware of the key elements useful to calculate the perioperative cardiovascular risk, and of the medical preventive treatment or further interventions to adopt in patients candidate to surgery.
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Affiliation(s)
- Pietro Amedeo Modesti
- Clinical Medicine and Cardiology, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy.
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Nagurney JT, Brown DFM, Chae C, Chang Y, Chung WG, Cranmer H, Dan L, Fisher J, Grossman S, Tedrow U, Lewandrowski K, Jang IK. The sensitivity of cardiac markers stratified by symptom duration. J Emerg Med 2005; 29:409-15. [PMID: 16243197 DOI: 10.1016/j.jemermed.2005.05.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2004] [Revised: 03/09/2005] [Accepted: 05/24/2005] [Indexed: 11/24/2022]
Abstract
We compared the sensitivity of three commonly used cardiac markers between two subpopulations, those who came to the Emergency Department (ED) late (6-24 h) after their symptoms began, and those who arrived earlier (<6 h), in a prospective comparative trial. Among all adult patients who presented to our ED with symptoms suggestive of acute myocardial infarction (MI), we drew serum for myoglobin, CK-MB, and troponin I upon arrival (time 0) and 2 h later. Outcomes, including acute MI, were determined. Sensitivities for all three markers between the subpopulations who arrived fewer than 6 h from symptom onset were compared to those who arrived later (6-24 h). We enrolled 346 eligible subjects, 36% of whom described cardiac symptoms as beginning 6 or more hours earlier; 14% suffered acute MIs. For time 0, the sensitivity of all three markers for acute MI was significantly higher among those subjects with symptoms of 6 or more hours' duration as compared to those with less. For troponin I, the increase in sensitivity between these two subpopulations approached 300%. At the time of the 2-h sample, the differences in sensitivities were much less and were not statistically significant. We conclude that cardiac marker values obtained at time 0 among Emergency Department patients who arrive 6 or more hours after cardiac symptom onset provide significantly higher sensitivities as compared to those obtained in patients who arrive earlier. For troponin I, the increase in sensitivity approaches threefold.
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Affiliation(s)
- John T Nagurney
- Massachusetts General Hospital, Boston, Massachusetts 02114, USA
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Abstract
Cardiac troponin (cT) is released after myocardial damage. In the appropriate clinical setting, a measured elevation of cT can increase the diagnostic rate of myocardial infarction and acute coronary syndrome. Elevations of cT, however, can occur in a wide variety of other clinical situations. Failure to recognize this can lead to an over-diagnosis of myocardial infarction (MI). We present clinical cases from our institution that illustrate this diagnostic problem, and review similar cases in the literature. We also discuss the implications of an erroneous diagnosis of myocardial infarction, for the patient and for the health services.
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Affiliation(s)
- C E Burness
- Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK
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Miller CD, Lindsell CJ, Khandelwal S, Chandra A, Pollack CV, Tiffany BR, Hollander JE, Gibler WB, Hoekstra JW. Is the initial diagnostic impression of “noncardiac chest pain” adequate to exclude cardiac disease? Ann Emerg Med 2004; 44:565-74. [PMID: 15573030 DOI: 10.1016/j.annemergmed.2004.03.021] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
STUDY OBJECTIVE In patients presenting to the emergency department (ED) with an initial diagnostic impression of noncardiac chest pain, we determine the 30-day incidence of adverse cardiac events and characteristics associated with those events. METHODS The multicenter, prospectively collected Internet Tracking Registry for Acute Coronary Syndromes (i*tr ACS ) registry of patients with chest pain enrolled from June 1, 1999, to August 1, 2001, was reviewed. We included patients if the physician's initial diagnostic impression was noncardiac chest pain after the medical history, physical examination, and initial 12-lead ECG. ED records, inpatient records, and follow-up results were reviewed for evidence of an adverse cardiac event defined as ST-segment or non-ST-segment elevation myocardial infarction, unstable angina, revascularization, or cardiac death within 30 days. RESULTS Of 17,737 patients enrolled in i*tr ACS , 2,992 had an initial emergency physician impression of noncardiac chest pain. Of these, 85 (2.8%) patients had definite evidence for an adverse cardiac event. The adverse cardiac event group was older (61.2 versus 47.9 years), more likely to be men (58.6% versus 38.7%), and had a higher Acute Cardiac Ischemia-Time Insensitive Predictive Instrument score (26.1 versus 15.6). Factors associated with adverse cardiac events included hypercholesterolemia, diabetes, history of coronary artery disease, and history of congestive heart failure. CONCLUSION When the initial impression is noncardiac chest pain, high-risk features such as traditional cardiovascular risk factors or a history of coronary artery disease are associated with adverse cardiac events. In the absence of well-defined criteria, treating physicians should consider further evaluation before diagnosing patients with noncardiac chest pain if these features are present.
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Affiliation(s)
- Chadwick D Miller
- Department of Emergency Medicine, Wake Forest University, Winston-Salem, NC 27157-1089, USA.
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Abstract
PURPOSE OF THE REVIEW Elevated levels of cardiac troponins, indicative of the presence of cardiac injury, have been reported in critically ill patients. In this review, the incidence, significance, and clinical relevance of elevated troponin levels among this group of patients will be discussed. RECENT FINDINGS It has been shown that elevated cardiac troponin levels can be present among critically ill septic patients without evidence of myocardial ischemia. Recent studies show that elevated troponin levels are also present in a diverse group of critically ill patients without sepsis or septic shock. In addition, several but not all studies show that the mortality rate of troponin-positive patients is significantly higher compared with troponin-negative patients. SUMMARY Elevated troponin levels are not only present in patients suffering from acute coronary syndromes but can also be present in critically ill patients. Even minor elevations are specific for myocardial injury. However, every elevated troponin level in the critically ill patient should not be rigorously diagnosed or treated as a myocardial infarction.
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