Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 24
Braz. j. med. biol. res ; 53(2): e9106, 2020. graf
Article in English | LILACS | ID: biblio-1055491


Reperfusion strategies in acute myocardial infarction (AMI) can cause a series of additional clinical damage, defined as myocardial ischemia/reperfusion (I/R) injury, and thus there is a need for effective therapeutic methods to attenuate I/R injury. miR-26a-5p has been proven to be an essential regulator for biological processes in different cell types. Nevertheless, the role of miR-26a-5p in myocardial I/R injury has not yet been reported. We established an I/R injury model in vitro and in vivo. In vitro, we used cardiomyocytes to simulate I/R injury using hypoxia/reoxygenation (H/R) assay. In vivo, we used C57BL/6 mice to construct I/R injury model. The infarct area was examined by TTC staining. The level of miR-26a-5p and PTEN was determined by bioinformatics methods, qRT-PCR, and western blot. In addition, the viability and apoptosis of cardiomyocytes were separately detected by MTT and flow cytometry. The targeting relationship between miR-26a-5p and PTEN was analyzed by the TargetScan website and luciferase reporter assay. I/R and H/R treatment induced myocardial tissue injury and cardiomyocyte apoptosis, respectively. The results showed that miR-26a-5p was down-regulated in myocardial I/R injury. PTEN was found to be a direct target of miR-26a-5p. Furthermore, miR-26a-5p effectively improved viability and inhibited apoptosis in cardiomyocytes upon I/R injury by inhibiting PTEN expression to activate the PI3K/AKT signaling pathway. miR-26a-5p could protect cardiomyocytes against I/R injury by regulating the PTEN/PI3K/AKT pathway, which offers a potential approach for myocardial I/R injury treatment.

Animals , Rabbits , Myocardial Reperfusion Injury/metabolism , Myocardial Ischemia/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Myocytes, Cardiac/pathology , MicroRNAs/metabolism , PTEN Phosphohydrolase/metabolism , Signal Transduction , Blotting, Western , Disease Models, Animal , Proto-Oncogene Proteins c-akt/metabolism , Real-Time Polymerase Chain Reaction , Flow Cytometry , Mice, Inbred C57BL
Article in English | WPRIM | ID: wpr-880589


Cardiomyocytes injury model has been widely used in the study for the molecular mechanism of cardiovascular diseases and drug action. It is very important to select the appropriate model due to the different formation mechanisms for various models. Clinical cardiovascular pathological change is relatively complex. Currently used models according to the characteristics of clinical cardiovascular diseases mainly include hydrogen peroxide-induced myocardial cell damage model, hypoxia reoxygenation injury model, adriamycin-induced myocardial cell damage model, high sugar high fat-induced myocardial cell damage model, and isoprenaline-induced myocardial cell damage model. Every model has its advantages as well as its disadvantages. The suitable model of myocardial cell injury can be selected according to the research purpose.

Animals , Cell Hypoxia , Myocardial Reperfusion Injury/metabolism , Myocardium , Myocytes, Cardiac/metabolism , Rats , Rats, Sprague-Dawley , Research
Acta cir. bras ; 34(11): e201901104, Nov. 2019. graf
Article in English | LILACS | ID: biblio-1054677


Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.

Animals , Male , Cardiotonic Agents/pharmacology , Myocardial Reperfusion Injury/prevention & control , NF-kappa B/drug effects , Genistein/pharmacology , Toll-Like Receptor 4/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/drug effects , Aspartate Aminotransferases/blood , Reference Values , Myocardial Reperfusion Injury/metabolism , Signal Transduction/drug effects , Blotting, Western , Reproducibility of Results , Cytokines/blood , NF-kappa B/metabolism , Rats, Sprague-Dawley , Creatine Kinase/blood , Lactate Dehydrogenases/blood , Toll-Like Receptor 4/metabolism , Anti-Inflammatory Agents/pharmacology
Acta cir. bras ; 34(11): e201901106, Nov. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054683


Abstract Purpose: To investigate whether GDF11 ameliorates myocardial ischemia reperfusion (MIR) injury in diabetic rats and explore the underlying mechanisms. Methods: Diabetic and non-diabetic rats subjected to MIR (30 min of coronary artery occlusion followed by 120 min of reperfusion) with/without GDF11 pretreatment. Cardiac function, myocardial infarct size, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) 15-F2tisoprostane, autophagosome, LC3II/I ratio and Belcin-1 level were determined to reflect myocardial injury, oxidative stress and autophagy, respectively. In in vitro study, H9c2 cells cultured in high glucose (HG, 30mM) suffered hypoxia reoxygenation (HR) with/without GDF11, hydrogen peroxide (H2O2) and autophagy inhibitor 3-methyladenine (3-MA) treatment, cell injury; oxidative stress and autophagy were assessed. Results: Pretreatment with GDF11 significantly improved cardiac morphology and function in diabetes, concomitant with decreased arrhythmia severity, infarct size, CK-MB, LDH and 15-F2tisoprostane release, increased SOD activity and autophagy level. In addition, GDF11 notably reduced HR injury in H9c2 cells with HG exposure, accompanied by oxidative stress reduction and autophagy up-regulation. However, those effects were completely reversed by H2O2 and 3-MA. Conclusion: GDF11 can provide protection against MIR injury in diabetic rats, and is implicated in antioxidant stress and autophagy up-regulation.

Animals , Male , Autophagy/drug effects , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/drug therapy , Oxidative Stress/drug effects , Diabetes Mellitus, Type 1/metabolism , Growth Differentiation Factors/pharmacology , Reference Values , Superoxide Dismutase/analysis , Cardiotonic Agents/pharmacology , Myocardial Reperfusion Injury/pathology , Up-Regulation/drug effects , Cell Line , Blotting, Western , Reproducibility of Results , Rats, Sprague-Dawley , Streptozocin , Microscopy, Electron, Transmission , Diabetes Mellitus, Experimental/metabolism , Hemodynamics/drug effects , Antioxidants/pharmacology
Acta cir. bras ; 34(8): e201900802, 2019. tab, graf
Article in English | LILACS | ID: biblio-1038128


Abstract Purpose To reveal the function of miR-134 in myocardial ischemia. Methods Real-time PCR and western blotting were performed to measure the expression of miR-134, nitric oxide synthase 3 (NOS3) and apoptotic-associated proteins. Lactic dehydrogenase (LDH) assay, cell counting kit-8 (CCK-8), Hoechst 33342/PI double staining and flow cytometry assay were implemented in H9c2 cells, respectively. MiR-134 mimic/inhibitor was used to regulate miR-134 expression. Bioinformatic analysis and luciferase reporter assay were utilized to identify the interrelation between miR-134 and NOS3. Rescue experiments exhibited the role of NOS3. The involvement of PI3K/AKT was assessed by western blot analysis. Results MiR-134 was high regulated in the myocardial ischemia model, and miR-134 mimic/inhibitor transfection accelerated/impaired the speed of cell apoptosis and attenuated/exerted the cell proliferative prosperity induced by H/R regulating active status of PI3K/AKT signaling. LDH activity was also changed due to the different treatments. Moreover, miR-134 could target NOS3 directly and simultaneously attenuated the expression of NOS3. Co-transfection miR-134 inhibitor and pcDNA3.1-NOS3 highlighted the inhibitory effects of miR-134 on myocardial H/R injury. Conclusion This present work puts insights into the crucial effects of the miR-134/NOS3 axis in myocardial H/R injury, delivering a potential therapeutic technology in future.

Animals , Rats , Myocardial Reperfusion Injury/metabolism , MicroRNAs/metabolism , Nitric Oxide Synthase Type III/metabolism , Hypoxia/metabolism , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/drug therapy , Signal Transduction/drug effects , Apoptosis/drug effects , Apoptosis/physiology , Phosphatidylinositol 3-Kinases/metabolism , MicroRNAs/genetics , MicroRNAs/therapeutic use , Cell Proliferation/drug effects , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism
Acta cir. bras ; 33(12): 1067-1077, Dec. 2018. graf
Article in English | LILACS | ID: biblio-973486


Abstract Purpose: To investigate the effect of alprostadil on myocardial ischemia/reperfusion (I/R) in rats. Methods: Rats were subjected to myocardial ischemia for 30 min followed by 24h reperfusion. Alprostadil (4 or 8 μg/kg) was intravenously administered at the time of reperfusion and myocardial infarct size, levels of troponin T, and the activity of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were measured. Antioxidative parameters, nitric oxide (NO) content and phosphorylated endothelial nitric oxide synthase 3 (p-eNOS) expression in the left ventricles were also measured. Histopathological examinations of the left ventricles were also performed. Results: Alprostadil treatment significantly reduced myocardial infarct size, serum troponin T levels, and CK-MB and LDH activity (P<0.05). Furthermore, treatment with alprostadil significantly decreased malondialdehyde (MDA) content (P<0.05) and markedly reduced myonecrosis, edema and infiltration of inflammatory cells. Superoxide dismutase and catalase activities (P<0.05), NO level (P<0.01) and p-eNOS (P<0.05) were significantly increased in rats treated with alprostadil compared with control rats. Conclusion: These results indicate that alprostadil protects against myocardial I/R injury and that these protective effects are achieved, at least in part, via the promotion of antioxidant activity and activation of eNOS.

Animals , Male , Alprostadil/pharmacology , Myocardial Reperfusion Injury/prevention & control , Nitric Oxide Synthase Type III/metabolism , Antioxidants/pharmacology , Superoxide Dismutase/analysis , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Catalase/analysis , Random Allocation , Blotting, Western , Reproducibility of Results , Treatment Outcome , Rats, Sprague-Dawley , Oxidative Stress/drug effects , Troponin T/drug effects , Troponin T/blood , Enzyme Activation/drug effects , Creatine Kinase, MB Form/drug effects , Creatine Kinase, MB Form/blood , Heart Ventricles/drug effects , Heart Ventricles/pathology , L-Lactate Dehydrogenase/drug effects , L-Lactate Dehydrogenase/blood , Malondialdehyde/analysis , Myocardial Infarction/pathology , Nitric Oxide/analysis
Arq. bras. cardiol ; 110(1): 44-51, Jan. 2018. graf
Article in English | LILACS | ID: biblio-887998


Resumo Background: Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland that is indicated to effectively prevent myocardial reperfusion injury. It is unclear whether melatonin protects cardiac function from reperfusion injury by modulating intracellular calcium homeostasis. Objective: Demonstrate that melatonin protect against myocardial reperfusion injury through modulating IP3R and SERCA2a to maintain calcium homeostasis via activation of ERK1 in cardiomyocytes. Methods: In vitro experiments were performed using H9C2 cells undergoing simulative hypoxia/reoxygenation (H/R) induction. Expression level of ERK1, IP3R and SERCA2a were assessed by Western Blots. Cardiomyocytes apoptosis was detected by TUNEL. Phalloidin-staining was used to assess alteration of actin filament organization of cardiomyocytes. Fura-2 /AM was used to measure intracellular Ca2+ concentration. Performing in vivo experiments, myocardial expression of IP3R and SERCA2a were detected by immunofluorescence staining using myocardial ischemia/ reperfusion (I/R) model in rats. Results: In vitro results showed that melatonin induces ERK1 activation in cardiomyocytes against H/R which was inhibited by PD98059 (ERK1 inhibitor). The results showed melatonin inhibit apoptosis of cardiomyocytes and improve actin filament organization in cardiomyocytes against H/R, because both could be reversed by PD98059. Melatonin was showed to reduce calcium overload, further to inhibit IP3R expression and promote SERCA2a expression via ERK1 pathway in cardiomyocytes against H/R. Melatonin induced lower IP3R and higher SERCA2a expression in myocardium that were reversed by PD98059. Conclusion: melatonin-induced cardioprotection against reperfusion injury is at least partly through modulation of IP3R and SERCA2a to maintain intracellular calcium homeostasis via activation of ERK1.

Resumo Fundamento: A melatonina é um hormônio neuroendócrino sintetizado principalmente pela glândula pineal que é indicado para prevenir efetivamente a lesão de reperfusão miocárdica. Não está claro se a melatonina protege a função cardíaca da lesão de reperfusão através da modulação da homeostase do cálcio intracelular. Objetivo: Demonstrar que a melatonina protege contra a lesão de reperfusão miocárdica através da modulação de IP3R e SERCA para manter a homeostase de cálcio por meio da ativação de ERK1 em cardiomiócitos. Métodos: Foram realizados experimentos in vitro usando células H9C2 submetidas a indução de hipoxia / reoxigenação simulada (H/R). O nível de expressão de ERK1, IP3R e SERCA foi avaliado por Western Blots. A apoptose de cardiomiócitos foi detectada por TUNEL. A coloração de faloidina foi utilizada para avaliar a alteração da organização de filamentos de actina dos cardiomiócitos. Fura-2 / AM foi utilizado para medir a concentração intracelular de Ca2+. Realizando experiências in vivo, a expressão miocárdica de IP3R e SERCA foi detectada por coloração com imunofluorescência usando modelo de isquemia miocárdica / reperfusão (I/R) em ratos. Resultados: resultados in vitro mostraram que a melatonina induz a ativação de ERK1 em cardiomiócitos contra H/R que foi inibida por PD98059 (inibidor de ERK1). Os resultados mostraram que a melatonina inibe a apoptose dos cardiomiócitos e melhora a organização do filamento de actina em cardiomiócitos contra H/R, pois ambas poderiam ser revertidas pela PD98059. A melatonina mostrou reduzir a sobrecarga de cálcio, além de inibir a expressão de IP3R e promover a expressão de SERCA através da via ERK1 em cardiomiócitos contra H/R. A melatonina induziu menor IP3R e maior expressão de SERCA no miocárdio que foram revertidas pela PD98059. Conclusão: a cardioproteção induzida pela melatonina contra lesão de reperfusão é pelo menos parcialmente através da modulação de IP3R e SERCA para manter a homeostase de cálcio intracelular via ativação de ERK1.

Animals , Male , Rats , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/prevention & control , MAP Kinase Signaling System/drug effects , Myocytes, Cardiac/drug effects , Sarcoplasmic Reticulum Calcium-Transporting ATPases/drug effects , Inositol 1,4,5-Trisphosphate Receptors/drug effects , Melatonin/pharmacology , Myocardial Reperfusion Injury/pathology , Rats, Sprague-Dawley , Myocytes, Cardiac/pathology , Disease Models, Animal , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Inositol 1,4,5-Trisphosphate Receptors/metabolism
Braz. j. med. biol. res ; 51(6): e6555, 2018. graf
Article in English | LILACS | ID: biblio-889109


Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of cardiovascular diseases, especially in myocardial infarction and ischemia/reperfusion (I/R). However, the underlying molecular mechanism remains unclear. In this study, we determined the role and the possible underlying molecular mechanism of lncRNA-ROR in myocardial I/R injury. H9c2 cells and human cardiomyocytes (HCM) were subjected to either hypoxia/reoxygenation (H/R), I/R or normal conditions (normoxia). The expression levels of lncRNA-ROR were detected in serum of myocardial I/R injury patients, H9c2 cells, and HCM by qRT-PCR. Then, levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) were measured by kits. Cell viability, apoptosis, apoptosis-associated factors, and p38/MAPK pathway were examined by MTT, flow cytometry, and western blot assays. Furthermore, reactive oxygen species (ROS) production was determined by H2DCF-DA and MitoSOX Red probes with flow cytometry. NADPH oxidase activity and NOX2 protein levels were measured by lucigenin chemiluminescence and western blot. Results showed that lncRNA-ROR expression was increased in I/R patients and in H/R treatment of H9c2 cells and HCM. Moreover, lncRNA-ROR significantly promoted H/R-induced myocardial injury via stimulating release of LDH, MDA, SOD, and GSH-PX. Furthermore, lncRNA-ROR decreased cell viability, increased apoptosis, and regulated expression of apoptosis-associated factors. Additionally, lncRNA-ROR increased phosphorylation of p38 and ERK1/2 expression and inhibition of p38/MAPK, and rescued lncRNA-ROR-induced cell injury in H9c2 cells and HCM. ROS production, NADPH oxidase activity, and NOX2 protein levels were promoted by lncRNA-ROR. These data suggested that lncRNA-ROR acted as a therapeutic agent for the treatment of myocardial I/R injury.

Humans , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/metabolism , RNA, Long Noncoding/metabolism , Apoptosis , Blotting, Western , Cell Survival , Glutathione Peroxidase/metabolism , Hydro-Lyases/metabolism , Malondialdehyde/metabolism , Myocardial Ischemia/genetics , Myocardial Reperfusion Injury/genetics , Myocytes, Cardiac , Real-Time Polymerase Chain Reaction , RNA, Long Noncoding/genetics , Signal Transduction , Superoxide Dismutase/metabolism , Transfection
An. acad. bras. ciênc ; 89(3): 1683-1690, July-Sept. 2017. graf
Article in English | LILACS | ID: biblio-886764


ABSTRACT Ischemia is responsible for many metabolic abnormalities in the heart, causing changes in organ function. One of modifications occurring in the ischemic cell is changing from aerobic to anaerobic metabolism. This change causes the predominance of the use of carbohydrates as an energy substrate instead of lipids. In this case, the glycogen is essential to the maintenance of heart energy intake, being an important reserve to resist the stress caused by hypoxia, using glycolysis and lactic acid fermentation. In order to study the glucose anaerobic pathways utilization and understand the metabolic adaptations, New Zealand white rabbits were subjected to ischemia caused by Inflow occlusion technique. The animals were monitored during surgery by pH and lactate levels. Transcription analysis of the pyruvate kinase, lactate dehydrogenase and phosphoenolpyruvate carboxykinase enzymes were performed by qRT-PCR, and glycogen quantification was determined enzymatically. Pyruvate kinase transcription increased during ischemia, followed by glycogen consumption content. The gluconeogenesis increased in control and ischemia moments, suggesting a relationship between gluconeogenesis and glycogen metabolism. This result shows the significant contribution of these substrates in the organ energy supply and demonstrates the capacity of the heart to adapt the metabolism after this injury, sustaining the homeostasis during short-term myocardial ischemia.

Animals , Male , Rabbits , Myocardial Reperfusion Injury/metabolism , Myocardial Ischemia/metabolism , Gluconeogenesis/physiology , Glycogen/metabolism , Myocardial Reperfusion Injury/physiopathology , Myocardial Ischemia/physiopathology , Disease Models, Animal
Arq. bras. cardiol ; 107(4): 339-347, Oct. 2016. tab, graf
Article in English | LILACS | ID: biblio-827852


Abstract Background: Coronary artery disease is 2-3 times more common in diabetic individuals. Dietary nitrate/nitrite has beneficial effects in both diabetes and cardiovascular disease. It also has protective effects against myocardial ischemia-reperfusion (IR) injury in healthy animals. However, the effects of nitrate on myocardial IR injury in diabetic rats have not yet been investigated. Objective: We examined the effects of dietary nitrate on myocardial IR injury in streptozotocin-nicotinamide-induced diabetic rats. Method: Rats were divided into four groups (n=7 in each group): control, control+nitrate, diabetes, and diabetes+nitrate. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Nitrate (sodium nitrate) was added to drinking water (100 mg/L) for 2 months. The hearts were perfused in a Langendorff apparatus at 2 months and assessed before (baseline) and after myocardial IR for the following parameters: left ventricular developed pressure (LVDP), minimum and maximum rates of pressure change in the left ventricle (±dP/dt), endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression, and levels of malondialdehyde (MDA) and NO metabolites (NOx). Results: Recovery of LVDP and ±dP/dt was lower in diabetic rats versus controls, but almost normalized after nitrate intake. Diabetic rats had lower eNOS and higher iNOS expression both at baseline and after IR, and dietary nitrate restored these parameters to normal values after IR. Compared with controls, heart NOx level was lower in diabetic rats at baseline but was higher after IR. Diabetic rats had higher MDA levels both at baseline and after IR, which along with heart NOx levels decreased following nitrate intake. Conclusion: Dietary nitrate in diabetic rats provides cardioprotection against IR injury by regulating eNOS and iNOS expression and inhibiting lipid peroxidation in the heart.

Resumo Fundamentos: A doença arterial coronariana é duas a três vezes mais comum em indivíduos diabéticos. O nitrato/nitrito dietético tem efeitos benéficos tanto para o diabetes quanto para a doença cardiovascular, assim como efeitos protetores contra a lesão de isquemia-reperfusão (IR) miocárdica em animais saudáveis. Porém, os efeitos do nitrato na lesão de IR miocárdica em ratos diabéticos ainda não foram investigados. Objetivos: Foram examinados os efeitos sobre a lesão de IR miocárdica da adição de nitrato à dieta de ratos com diabetes mellitus tipo 2 induzido por estreptozotocina-nicotinamida. Métodos: Os ratos foram divididos em quatro grupos (n = 7 em cada grupo): controle, controle+nitrato, diabetes e diabetes+nitrato. O diabetes foi induzido nos animais por injeção de estreptozotocina e nicotinamida. Nitrato (nitrato de sódio) foi adicionado à água de beber (100 mg/L) por 2 meses. Os corações foram perfundidos em sistema de Langendorff aos 2 meses e avaliados antes (basal) e após IR miocárdica em relação aos seguintes parâmetros: pressão desenvolvida no ventrículo esquerdo (PDVE), taxas máximas de variação positiva e negativa da pressão ventricular esquerda (±dP/dt), expressão do RNAm da óxido nítrico (NO) sintase (NOS) endotelial (eNOS) e da NOS induzível (iNOS), além de níveis de malondialdeído (MDA) e metabólitos do óxido nítrico (NOx). Resultados: A recuperação da PDVE e ±dP/dt foi inferior nos ratos diabéticos versus controles, mas quase normalizou após ingestão de nitrato. Ratos diabéticos apresentaram expressão diminuída de eNOS e aumentada de iNOS tanto no estado basal quanto após IR, e o consumo dietético de nitrato restaurou estes valores para o estado normal após a IR. O nível de NOx cardíaco foi menor nos ratos diabéticos em comparação aos controles no momento basal, mas foi superior após a IR. Ratos diabéticos apresentaram níveis mais elevados de MDA tanto no estado basal quanto após IR que, juntamente com os níveis cardíacos de NOx, reduziram após consumo dietético do nitrato. Conclusões: O consumo dietético de nitrato por ratos diabéticos ofereceu cardioproteção contra a lesão de IR através da regulação da expressão de eNOS e iNOS e inibição da peroxidação lipídica no coração.

Animals , Male , Cardiotonic Agents/therapeutic use , Myocardial Reperfusion Injury/prevention & control , Myocardial Ischemia/prevention & control , Diabetes Mellitus, Type 2/complications , Nitrates/therapeutic use , Lipid Peroxidation/physiology , Myocardial Reperfusion Injury/physiopathology , Myocardial Reperfusion Injury/metabolism , Reproducibility of Results , Treatment Outcome , Myocardial Ischemia/physiopathology , Myocardial Ischemia/metabolism , Streptozocin , Coronary Vessels/physiopathology , Coronary Vessels/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/metabolism , Hemodynamics , Malondialdehyde/analysis
Arq. bras. cardiol ; 106(1): 41-48, Jan. 2016. tab, graf
Article in Portuguese | LILACS | ID: lil-771055


Abstract Background: Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease. Objective: To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats. Method: SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (±dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study. Results: In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p < 0.05) lower, and HR (32%) was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days. Conclusion: Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.

Resumo Fundamento: A privação de sono (PS) acha-se fortemente associada a alto risco cardiovascular. Objetivo: Determinar o efeito da PS nas funções hemodinâmicas basais e tolerância à lesão miocárdica de isquemia‑reperfusão (IR) em ratos machos. Métodos: A PS foi induzida com o método da plataforma única por 4 dias. Utilizou-se o modelo de perfusão de coração isolado de Langendorff, medindo-se os seguintes parâmetros nas condições basais e após IR: pressão desenvolvida no ventrículo esquerdo (PDVE), frequência cardíaca (FC) e taxa máxima de aumento e redução da pressão do ventrículo esquerdo (±dp/dt). O nível cardíaco de NOx, o tamanho do infarto e os níveis de CK-MB e LDH no efluente coronário foram medidos após IR. A pressão arterial sistólica (PAS) foi medida no início e no final do estudo. Resultados: No grupo PS, os valores basais de PDVE (19%), +dp/dt (18%) e-dp/dt (21%) foram significativamente mais baixos (p < 0,05), e a FC (32%) significativamente mais alta em comparação aos dos controles. Após isquemia, os corações do grupo PS apresentavam um significativo aumento da FC além de uma menor recuperação da função hemodinâmica em comparação aos dos controles. No grupo PS, os níveis de NOx no coração e de CK-MB e LDH no efluente coronário, além do tamanho do infarto, foram significativamente maiores após IR. O grupo PS também apresentou maior PAS após 4 dias. Conclusão: Os corações do grupo PS apresentaram menor função cardíaca basal e menor tolerância à lesão de IR, o que pode estar relacionado ao aumento da produção de NO após IR.

Animals , Male , Heart/physiopathology , Hemodynamics/physiology , Myocardial Reperfusion Injury/physiopathology , Sleep Deprivation/physiopathology , Blood Pressure/physiology , Creatine Kinase, MB Form/analysis , L-Lactate Dehydrogenase/analysis , Myocardial Infarction , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Nitric Oxide/analysis , Nitric Oxide/metabolism , Random Allocation , Rats, Wistar , Reference Values , Risk Factors , Sleep Deprivation/metabolism , Time Factors
Arq. bras. cardiol ; 105(1): 71-81, July 2015. tab, ilus
Article in English | LILACS | ID: lil-755009



Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate.


To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury.


A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies.


The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review.


On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions.



O infarto agudo do miocárdio é a principal causa de mortalidade e de morbidade na população mundial. Por outro lado, pesquisas já demonstraram que o exercício físico, além de reduzir os fatores de risco cardiovascular, também é capaz de promover cardioproteção contra lesões por isquemia e reperfusão, por meio de um efeito direto no miocárdio. No entanto, o mecanismo específico envolvido no pré-condicionamento cardíaco induzido pelo exercício ainda é alvo de discussão.


Realizar uma revisão sistemática acerca dos estudos que se debruçaram sobre os mecanismos pelos quais o exercício físico aeróbio promove cardioproteção direta contra lesões por isquemia e reperfusão.


Foi realizada uma pesquisa nas seguintes bases de dados: MEDLINE, LILACS e SciELO. Os dados foram extraídos de forma padronizada, por dois investigadores independentes, responsáveis pela avaliação da qualidade metodológica dos manuscritos.


A busca inicial resultou em 78 estudos, dos quais, após revisão dos resumos, 30 foram excluídos. Os 48 manuscritos restantes foram lidos na íntegra e, destes, 20 foram excluídos, restando 28 estudos incluídos nesta revisão sistemática.


Com base nos estudos selecionados, os seguintes mecanismos estão potencialmente envolvidos na resposta cardioprotetora do exercício: aumento na produção de proteínas de choque térmico; envolvimento da via do óxido nítrico; aumento na capacidade antioxidativa cardíaca; melhora na função dos canais de potássio dependentes de ATP; e ativação do sistema de opióides. Apesar de todo o investimento já realizado, ainda é necessário mais investimento em trabalhos futuros, para obtenção de conclusão mais consistente.


Humans , Exercise Therapy/methods , Exercise/physiology , Myocardial Infarction/metabolism , Myocardial Reperfusion Injury/metabolism , Antioxidants/metabolism , Heat-Shock Proteins/metabolism , KATP Channels/metabolism , Myocardial Infarction/physiopathology , Myocardial Infarction/prevention & control , Myocardial Reperfusion Injury/physiopathology , Myocardial Reperfusion Injury/prevention & control , Time Factors
Rev. bras. cir. cardiovasc ; 29(2): 249-254, Apr-Jun/2014. tab, graf
Article in Portuguese | LILACS | ID: lil-719408


O paradoxo do cálcio foi pela primeira vez citado em 1966 por Zimmerman et al. A partir daí, ganhou grande interesse por parte da comunidade científica internacional devido ao fato da ausência do íon cálcio produzir na célula muscular cardíaca dano semelhante à lesão de isquemia-reperfusão. Apesar de não serem conhecidos todos os mecanismos envolvidos no processo da lesão celular no paradoxo do cálcio, a conexão intercelular mantida somente pelo nexus parece ter papel chave na fragmentação celular. A adição de pequenas concentrações de cálcio, bloqueadores de canal de cálcio, hiponatremia ou hipotermia são importantes para evitar que haja lesão celular no momento da reperfusão com soluções com concentração fisiológica de cálcio.

The calcium paradox was first mentioned in 1966 by Zimmerman et al. Thereafter gained great interest from the scientific community due to the fact of the absence of calcium ions in heart muscle cells produce damage similar to ischemia-reperfusion. Although not all known mechanisms involved in cellular injury in the calcium paradox intercellular connection maintained only by nexus seems to have a key role in cellular fragmentation. The addition of small concentrations of calcium, calcium channel blockers, and hyponatraemia hypothermia are important to prevent any cellular damage during reperfusion solutions with physiological concentration of calcium.

Animals , Humans , Rats , Calcium/metabolism , Heart Injuries/metabolism , Myocytes, Cardiac/metabolism , Adenosine Triphosphate/metabolism , Cell Membrane Permeability , Caffeine/adverse effects , Calcium Channel Blockers/pharmacology , Calcium/administration & dosage , Dinitrophenols/metabolism , Glycocalyx/metabolism , Heart Failure/etiology , Heart Injuries/etiology , Heart Injuries/pathology , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Sodium/physiology , Time Factors
Braz. j. med. biol. res ; 45(10): 898-905, Oct. 2012. ilus, tab
Article in English | LILACS | ID: lil-647748


The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE) pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S) postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g) were divided into 6 groups (N = 14 per group): time-matched perfusion (Sham) group, ischemia/reperfusion (I/R) group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 µM) group, and dimethyl sulfoxide (DMSO; <0.2%) group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of increase or decrease of left ventricular pressure (± dp/dt max) were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC) staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05) and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05). However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.

Animals , Male , Rats , Hydrogen Sulfide/metabolism , Ischemic Postconditioning , /metabolism , Myocardial Reperfusion Injury/metabolism , /metabolism , Apoptosis , /analysis , Rats, Sprague-Dawley , Signal Transduction , /analysis , Tyrphostins
Article in English | WPRIM | ID: wpr-119890


Sauchinone has been known to have anti-inflammatory and antioxidant effects. We determined whether sauchinone is beneficial in regional myocardial ischemia/reperfusion (I/R) injury. Rats were subjected to 20 min occlusion of the left anterior descending coronary artery, followed by 2 hr reperfusion. Sauchinone (10 mg/kg) was administered intraperitoneally 30 min before the onset of ischemia. The infarct size was measured 2 hr after resuming the perfusion. The expression of cell death kinases (p38 and JNK) and reperfusion injury salvage kinases (phosphatidylinositol-3-OH kinases-Akt, extra-cellular signal-regulated kinases [ERK1/2])/glycogen synthase kinase (GSK)-3beta was determined 5 min after resuming the perfusion. Sauchinone significantly reduced the infarct size (29.0% +/- 5.3% in the sauchinone group vs 44.4% +/- 6.1% in the control, P < 0.05). Accordingly, the phosphorylation of JNK and p38 was significantly attenuated, while that of ERK1/2, Akt and GSK-3beta was not affected. It is suggested that sauchinone protects against regional myocardial I/R injury through inhibition of phosphorylation of p38 and JNK death signaling pathways.

Animals , Benzopyrans/pharmacology , Dioxoles/pharmacology , Glycogen Synthase Kinase 3/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Myocardial Reperfusion Injury/metabolism , Phosphorylation , Protective Agents/pharmacology , Rats , Signal Transduction/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism
Article in English | WPRIM | ID: wpr-44281


Activated protein C (APC) is known to be beneficial on ischemia reperfusion injury in myocardium. However, the protection mechanism of APC is not fully understood. The purpose of this study was to investigate the effects and possible mechanisms of APC on myocardial ischemic damage. Artificially ventilated anaesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 hr of reperfusion. Rats were randomly divided into four groups; Sham, I/R, APC preconditioning and postconditioning group. Myocardial infarct size, apoptosis index, the phosphorylation of ERK1/2, Bcl-2, Bax and cytochrome c genes and proteins were assessed. In APC-administrated rat hearts, regardless of the timing of administration, infarct size was consistently reduced compared to ischemia/reperfusion (I/R) rats. APC improved the expression of ERK1/2 and anti-apoptotic protein Bcl-2 which were significantly reduced in the I/R rats. APC reduced the expression of pro-apoptotic genes, Bax and cytochrome c. These findings suggest that APC produces cardioprotective effect by preserving the expression of proteins and genes involved in anti-apoptotic pathways, regardless of the timing of administration.

Animals , Apoptosis , Cytochromes c/genetics , Hemodynamics/physiology , Male , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Phosphorylation , Protein C/therapeutic use , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , bcl-2-Associated X Protein/metabolism
Article in English | WPRIM | ID: wpr-49343


Oxidative stress is critical for causing cardiac injuries during ischemia-reperfusion (IR), yet the molecular mechanism for this remains unclear. In the present study, we observe that hypoxia and reoxygenation, a component of ischemia, effectively induces apoptosis in the cardiac myocytes from neonatal rats and it concomitantly leads to induction of GADD153, an apoptosis-related gene. Furthermore, IR injury of rat heart showed a GADD153 overexpression in the ischemic area where the TUNEL reaction was positive. A downregulation of cardiac ankyrin repeat protein (CARP) was also observed in this ischemic area. Promoter deletion and reporter analysis revealed that hypoxia transcriptionally activates a GADD153 promoter through the AP-1 element in neonatal cardiomyocytes. Ectopic overexpression of GADD153 resulted in the downregulation of CARP expression. Accordingly, the induction of GADD153 mRNA were followed by the CARP down-regulation in an in vivo rat coronary ischemia/reperfusion injury model. These results suggest that GADD153 over-expression and the resulting downregulation of CARP may have causative roles in apoptotic cell death during cardiac IR injury.

Animals , Animals, Newborn , Hypoxia , Apoptosis/physiology , Cells, Cultured , Humans , Male , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Myocytes, Cardiac/cytology , Nuclear Proteins/genetics , Promoter Regions, Genetic , Rats , Rats, Sprague-Dawley , Repressor Proteins/genetics , Transcription Factor AP-1/genetics , Transcription Factor CHOP/genetics
Article in English | IMSEAR | ID: sea-24741


BACKGROUND & OBJECTIVES: Erythropoietin (EPO), originally identified for its critical hormonal role in promoting erythrocyte survival and differentiation, has shown to a protective effect in myocardial ischaemia-reperfusion (I-R) injury in animal model. However, the precise mechanisms remain unclear. The objective of this study was to determine the roles of nuclear factor-kappa B (NF-kB) and associated cytokines induced by I-R in the cardioprotection by recombinant human erythropoietin (rhEPO). Morphopathological observations were also made on the ultrastructure of myocardial tissue. METHODS: Myocardial I-R rat model was established by 30 min ligation of left descending coronary and 3 h reperfusion. RhEPO or saline solution was intraperitoneally injected 24 h before I-R insult. The infarct sizes were measured by triphenyltetrazolium chloride (TTC)-Evans blue technique and ultrastructural organizations were observed by a transmission electron microscope. Tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-10 concentrations were analyzed by enzyme-linked immunosorbance assays and NF-kB by electrophoretic mobility shift assay. TNF-alpha and IL-6 mRNA expression were studied by the reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: A single bolus injection of 5,000 units/kg of rhEPO 24 h before insult remarkably reduced infarct size and improved ultrastructural organization of I-R myocardium. It greatly suppressed TNF-alpha and IL-6 expression, but enhanced IL-10 production. It modestly activated NF-kB before I-R insult and markedly attenuated subsequent NF-kB activation during sustained I-R. INTERPRETATION & CONCLUSION: The suppression of proinflammatory cytokines expression may act by inhibiting NF-kB activation during I-R, but not by induction of IL-10. This might be one of the molecular mechanisms of rhEPO in cardioprotection. In addition, NF-kB was suggested to play a dual role in cardioprotective effects of rhEPO.

Analysis of Variance , Animals , Cytokines/metabolism , DNA Primers , Electrophoretic Mobility Shift Assay , Enzyme-Linked Immunosorbent Assay , Erythropoietin/metabolism , Ischemic Preconditioning, Myocardial/methods , Male , Microscopy, Electron, Transmission , Myocardial Reperfusion Injury/metabolism , Myocardium/ultrastructure , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction
Braz. j. med. biol. res ; 38(3): 345-352, mar. 2005. ilus
Article in English | LILACS | ID: lil-394809


Mitochondrial ion transport, oxidative phosphorylation, redox balance, and physical integrity are key factors in tissue survival following potentially damaging conditions such as ischemia/reperfusion. Recent research has demonstrated that pharmacologically activated inner mitochondrial membrane ATP-sensitive K+ channels (mitoK ATP) are strongly cardioprotective under these conditions. Furthermore, mitoK ATP are physiologically activated during ischemic preconditioning, a procedure which protects against ischemic damage. In this review, we discuss mechanisms by which mitoK ATP may be activated during preconditioning and the mitochondrial and cellular consequences of this activation, focusing on end-effects which may promote ischemic protection. These effects include decreased loss of tissue ATP through reverse activity of ATP synthase due to increased mitochondrial matrix volumes and lower transport of adenine nucleotides into the matrix. MitoK ATP also decreases the release of mitochondrial reactive oxygen species by promoting mild uncoupling in concert with K+/H+ exchange. Finally, mitoK ATP activity may inhibit mitochondrial Ca2+ uptake during ischemia, which, together with decreased reactive oxygen release, can prevent mitochondrial permeability transition, loss of organelle function, and loss of physical integrity. We discuss how mitochondrial redox status, K+ transport, Ca2+ transport, and permeability transitions are interrelated during ischemia/reperfusion and are determinant factors regarding the extent of tissue damage.

Humans , Mitochondria, Heart/metabolism , Myocardial Reperfusion Injury/metabolism , Potassium Channels/physiology , Biological Transport , Ischemic Preconditioning, Myocardial , Membrane Potentials/physiology , Myocardial Ischemia/metabolism , Oxidative Stress , Phosphorylation , Potassium Channels/metabolism , Potassium/metabolism
Arch. cardiol. Méx ; 73(4): 284-290, ilus, tab
Article in Spanish | LILACS | ID: lil-773408


En este artículo, se hacen algunas consideraciones en torno al daño miocárdico debido a déficit de aporte sanguíneo. En realidad, la alteración primordial del síndrome no consiste en la isquemia en sentido electrofisiopatológico, que es un trastorno de la repolarización celular debido a diferentes causas. Dicha alteración constituye más propiamente una despolarización diastólica parcial o lesión, i. e. una reducción moderada del potencial de reposo transmembrana. Caracteriza ésta la fase aguda del síndrome de infarto miocárdico y es responsable de las manifestaciones eléctricas, que aparecen en tal fase: desórdenes del ritmo y de la conducción, así como reducción de la contractilidad de las fibras miocárdicas afectadas. Estos fenómenos se deben a una falla de los mecanismos energéticos del miocardio por alteraciones mitocondriales de los miocitos: reducción temprana de los nucleótidos de nicotinamida adenina, acumulación de calcio ("calcium overload") en las mitocondrias y caída de la fosforilación oxidativa. Tales hechos pueden volver a presentarse, con mayor intensidad, en una fase posterior del síndrome de infarto por reperfusión miocárdica. Su gravedad está relacionada con la duración del período inicial de déficit de aporte sanguíneo al miocardio. Se les pueden agregar las consecuencias de un estrés oxidativo, responsable de la formación de especies reactivas derivadas del oxígeno. Dicho estrés causa daño también en el DNA mitocondrial produciendo mutaciones e inserción y pérdida de secuencias por oxidación de las bases nitrogenadas. Tanto en la fase de isquemia inicial como en la de reperfusión, puede ser muy útil la llamada terapéutica metabólica, p. ej. en su modalidad de las soluciones glucosa-insulina-potasio (G-I-K), que actuarían como acarreadoras de radicales libres derivados del oxígeno. Asimismo los llamados fármacos metabólicos, p. ej. la trimetazidina, los antioxidantes, etc., pueden ser útiles en la fase de reperfusión miocárdica.

In this article, we present some considerations on the myocardial damage due to a deficit of oxygen supply. In fact, this damage properly constitutes a partial diastolic depolarization or injury, i. e., a moderate reduction of the rest transmembrane potential. This phenomenon is characteristic of the acute phase of the myocardial infarction syndrome and is responsible for the main electrical manifestations appearing in this phase: disorders of rhythm and conduction, as well as a reduced contractility of the involved myocardial fibers. All the mentioned phenomena are due to a defect of the myocardial energetic mechanisms, owing to the mitochondrial alterations in myocytes: early reduction of the nicotinamide adenine nucleotides, accumulation of calcium ("calcium overload") into mitochondria, and a drop in oxidative phosphorylation. These changes can present again, more exaggerated, in a following phase of evolution of the myocardial infarction due to myocardial reperfusion. Its severity is related to the duration of the initial ischemia period. Moreover, consequences of the oxidative stress can add producing cellular damage by liberation of reactive oxygen species. Oxidant stress causes also alterations in the mitochondrial DNA, i. e., mutations due to oxidation of nitrogenous bases. During the initial ischemia phase, as well as during reperfusion, metabolic therapy can be very useful as, for example, glucose-insulin-potassium solutions (G-I-K). These could act as scavengers of the free radicals derived from oxygen and avoid or reduce the myocardial damage due to reperfused myocytes. Metabolic drugs, as for example tri-metazidine, antioxidants, etc, can also be used in the myocardial reperfusion phase. (Arch Cardiol Mex 2003; 73:284-290).

Humans , Myocardial Reperfusion Injury , Electrophysiology , Mitochondria/metabolism , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocardial Reperfusion Injury/therapy , Oxidative Stress