GDF11 ameliorated myocardial ischemia reperfusion injury by antioxidant stress and up-regulating autophagy in STZ-induced type 1 diabetic rats

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.

Effect of miR-134 against myocardial hypoxia/reoxygenation injury by directly targeting NOS3 and regulating PI3K/Akt pathway

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.

Alprostadil attenuates myocardial ischemia/reperfusion injury by promoting antioxidant activity and eNOS activation in rats

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.

Acetaminophen mitigates myocardial injury induced by lower extremity ischemia-reperfusion in rat model

Abstract Objective: The injury-reducing effect of acetaminophen, an effective analgesic and antipyretic on ischemia-reperfusion continues to attract great attention. This study analyzed the protective effect of acetaminophen on myocardial injury induced by ischemia-reperfusion in an experimental animal model from lower extremity ischemia-reperfusion. Methods: Twenty-four Sprague-Dawley female rats were randomized into three groups (n=8) as (i) control group (only laparotomy), (ii) aortic ischemia-reperfusion group (60 min of ischemia and 120 min of reperfusion) and (iii) ischemia-reperfusion + acetaminophen group (15 mg/kg/h intravenous acetaminophen infusion starting 15 minutes before the end of the ischemic period and lasting till the end of the reperfusion period). Sternotomy was performed in all groups at the end of the reperfusion period and the heart was removed for histopathological examination. The removed hearts were histopathologically investigated for myocytolysis, polymorphonuclear leukocyte (PMNL) infiltration, myofibrillar edema and focal hemorrhage. Results: The results of histopathological examination showed that acetaminophen was detected to particularly diminish focal hemorrhage and myofibrillar edema in the ischemia-reperfusion + acetaminophen group (P<0.001, P=0.011), while there were no effects on myocytolysis and PMNL infiltration between the groups (P=1.000, P=0.124). Conclusion: Acetaminophen is considered to have cardioprotective effect in rats, by reducing myocardial injury induced by abdominal aortic ischemia-reperfusion.

Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1 / Efeitos Protetores Induzidos pela Melatonina nos Cardiomiócitos Contra Lesões de Reperfusão Parcialmente Através da Modulação Dde IP3R e SERCA por Meio da Ativação de ERK1

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.

Protective effects of fentanyl preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion in rats

We aimed to study the effect of fentanyl (Fen) preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion (I/R) in rats. A total of 120 Sprague Dawley male rats (age: 3 months) were randomly divided into: sham operation group (S group), I/R group, normal saline I/R group (NS group), and fentanyl low, middle, and high dose groups (Fen1: 2 μg/kg; Fen2: 4 μg/kg; Fen3: 6 μg/kg). Heart rate (HR), mean arterial pressure (MAP), left ventricular developed pressure (LVDP), ±dp/dtmax, malondialdehyde (MDA), superoxide dismutase (SOD) activity, creatine phosphokinase-MB (CK-MB), and cardiac troponin-I (cTnI) were measured. Myocardial ischemic (MI) area, total apoptotic myocardial cells, and protein and mRNA expressions of B-cell lymphoma 2 (Bcl-2) and Bax were detected. HR and MAP were higher, while LVDP and ±dp/dtmax were close to the base value in the Fen groups compared to those in the I/R group. Decreased MDA concentration and CK-MB value and increased SOD activity were found in the Fen groups compared to the I/R group, while cTnI concentration was significantly lower in the Fen1 and Fen2 groups (all P<0.05). Myocardial damage was less in the Fen groups compared to the I/R group and the MI areas and apoptotic indexes were significantly lower in the Fen1 and Fen2 groups (all P<0.05). Furthermore, significantly increased protein and mRNA expressions of Bcl-2, and decreased protein and mRNA expressions of Bax were found in the Fen groups compared to the I/R group (all P<0.05). Fentanyl preconditioning may suppress cardiomyocyte apoptosis induced by I/R in rats by regulating Bcl-2 and Bax.

Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats / Tramadol Atenua Lesões Miocárdicas Induzidas pela Reperfusão Pós- Isquêmica Aguda de Membros Posteriores em Ratos

AbstractBackground:Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR) causes both remote organ and local injuries.Objective:This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR.Methods:Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham), Group II (IR), and Group III (IR + tramadol). Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous) was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination.Results:The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were higher in Groups I and III than those in Group II (p < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in Group II were significantly increased (p < 0.05), and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05) compared with Group II.Conclusion:From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

ResumoFundamento:Lesões a órgãos ocorrem não apenas durante períodos de isquemia, mas paradoxalmente, também durante a reperfusão. Sabe-se que a reperfusão pós-isquêmica (RPI) causa lesões tanto remotas quanto locais no órgão afetado.Objetivo:Este estudo avaliou os efeitos do tramadol no coração como órgão remoto, após RPI aguda dos membros posteriores.Métodos:Trinta ratos Wistar, machos, adultos e saudáveis, foram distribuídos aleatoriamente em três grupos: Grupo I (controle), Grupo II (RPI) e Grupo III (RPI + tramadol). Isquemia foi induzida em ratos anestesiados através do pinçamento da artéria femoral esquerda por 3 horas, seguidas de 3 horas de reperfusão. Tramadol foi administrado (20 mg/kg, IV) imediatamente antes da reperfusão. Ao final da reperfusão, os animais foram sacrificados e seus corações coletados para exames histológicos e bioquímicos.Resultados:Os níveis de superóxido-dismutase (SOD), catalase (CAT) e glutationa-peroxidase (GPx) foram maiores nos grupos I e III que no grupo II (p < 0.05). Em comparação aos outros grupos, os níveis tissulares de malondialdeído (MDA) estavam significativamente mais elevados no grupo II (p < 0.05), o que foi evitado pelo uso de tramadol. Foram pontuadas as alterações histopatológicas, incluindo micro-hemorragia, edema, infiltração por neutrófilos e necrose. A pontuação total das lesões do grupo III foi significativamente menor (p < 0.05) em comparação ao grupo II.Conclusão:Do ponto de vista histológico e bioquímico, o tratamento com tramadol diminuiu as lesões miocárdicas induzidas pela RPI da musculatura esquelética neste modelo experimental.

Selective cyclooxygenase-2 inhibition protects against myocardial damage in experimental acute ischemia

BACKGROUND: Acute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated. GOAL: The objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib) could alter the evolution of acute myocardial infarction after reperfusion. METHODS AND RESULTS: This study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow. The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I. CONCLUSION: In a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis.

El papel del factor de transcripción NF-κB en la célula cardíaca / Role of the transcription factor NF-κB in the cardiac cell

Para la biología de hoy las vías de señalización intracelular que controlan los procesos entre la vida y la muerte celular son de gran interés. Al respecto, el NF-κB destaca como un factor de transcripción decisivo de respuesta rápida que participa en la activación de las vías de señalización de la muerte celular programada. Lo relevante es que sus efectos tienen consecuencias en el desarrollo normal y/o la homeostasis en muchas células o tejidos, que incluyen entre otros al sistema inmune, los folículos capilares, apéndices epidermales, el riñon y el sistema nervioso. En esta revisión analizamos el papel central que juega el factor de transcripción NF-κB en el funcionamiento normal de la célula cardíaca y sus implicaciones en algunas de las patologías cardíacas más frecuentes como: el daño por isquemia-reperfusión, la isquemia precondicionada, la hipertrofia, la aterosclerosis, y el paro cardíaco. El NF-κB comúnmente funciona como un agente citoprotector, aunque hay algunos casos en los cuales resulta ser pro-apoptótico dependiendo del estímulo y del contexto celular. Se han logrado avances significativos a nivel molecular, que han permitido entender su modo de acción y el papel interactivo que juega con otros factores claves. Estos estudios han identificado muchos genes anti-apoptóticos y pro-apoptóticos regulados por la actividad del NF-κB abriendo novedosas aproximaciones que se pueden hacer sobre sus efectos en el desarrollo de patologías cardíacas.

The signaling pathways that control the life-death switch of a cell are a prime interest in Modern Biology. To this respect, NF-κB has emerged as a decisive transcription factor in the cell's response to apoptotic challenge and its effects on apoptosis have far-reaching consequences for normal development and/or homeostasis in many cells and tissues, including the immune system, hair follicles, and epidermal appendages, the liver, and nervous system. In this review we analyze the pivotal role of the transcription factor NF-κB in the normal functioning of the cardiac cell and its implication on some of the most frequent cardiac pathologies, such as ischemia-reperfusion injury, ischemic precondition, hypertrophy, atherosclerosis and cardiac arrest. While NF-κB is commonly found to be cytoprotective, there are a number of instances where it is proapoptotic depending on the inducing stimulus and the cell context. Significant progress has been made in understanding its mode of action and its interplay with other key factors. These studies identified many anti- and pro-apoptotic NF-κB regulated genes that mediate its activity, these important new insights fuel hope that novel approaches will be developed to control the effects of NF-κB in cardiac pathologies.

Consideraciones sobre el daño miocárdico por isquemia y reperfusión / Considerations on the myocardial damage due to ischemia and reperfusion

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).

The expression of Bcl-2 protein on acute myocardial ischemia/reperfusion and the significance in forensic pathology / 法医学杂志

OBJECTIVE@#To search the objective morphologic evidence for the forensic pathological diagnosis on the acute myocardial ischemia/reperfusion.@*METHODS@#The expression of Bcl-2 protein in the early stage of acute myocardial ischemia/reperfusion(I/R) in rats were studyed with immunohistochemistry.@*RESULTS@#There was no expression of Bcl-2 protein in control group. The expression of Bcl-2 protein began to increase in myocytes 0.5 h after I/R in the ischemic areas and the expression of Bcl-2 protein in inner layer was stronger than in outer layer. The expression of Bcl-2 protein appears firstly in the inner layer of myocardium and extended gradually toward the outer layer 1 h after I/R. It was found that the expression of Bcl-2 protein in outer layer was stronger than in inner layer, then the expression of Bcl-2 protein became weaken gradually.@*CONCLUSION@#Bcl-2 gene may be an important regulative gene in the process of apoptosis and the changes observed in this paper might be useful for the forensic pathological diagnosis on the early myocardial ischemia.

Efecto protector del dantrolene en las lesiones miocárdicas producidas por la reperfusión post-isquémica / Protective effect of dantrolene in post-ischemic reperfusion myocardial damage

Este estudio muestra que la hidantoína, dantrolene, protege al miocardio de las lesiones ocasionadas por la reperfusión post-isquémica. Este efecto, fue analizado después de ocluir durante 5 minutos la arteria coronaria izquierda de corazones de ratas Wistar. Los resultados evidencian que el dantrolene, a dosis de 1 mg/Kg, es efectivo para proteger al miocardio de las arritmias ventriculares y la disfunción contráctil ocasionadas por la isquemia-reperfusión. Además, disminuye la liberación de las enzimas creatina cinasa y lactato deshidrogenasa al plasma y protege al miocardio del daño estructural. Proponemos que esta acción protectora, puede deberse a un efecto bloqueador del canal liberador de calcio (canal de rianodina) del retículo sarcoplásmico, disminuyendo de este modo la sobrecarga de calcio sarcoplasmico, característico de la lesión por reperfusión

Effect of N-acetylcysteine on myocardial infarct size following ischemia and reperfusion in dogs.

The present study was designed to examine the role of N-acetylcysteine (NAC) on free radical mediated reperfusion injury in canine model. Fourteen dogs underwent 90 min of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Treated animals received loading dose of NAC (250 mg/kg) at the time of reperfusion upto 1 h followed by maintenance dose (70 mg/kg) for remaining 3 h through left atrial line. Infarct size, myocardial tissue lipid peroxidation, superoxide dismutase (SOD) and glutathione (GSH) levels were measured at the end of reperfusion in treated (n = 7) and untreated animals (n = 7). Left ventricular end diastolic pressure was significantly lower in treated animals compared to untreated group. SOD and GSH levels in myocardial tissue at risk and in infarcted zone were similar in both groups. However, in NAC treated animals the lipid peroxidation was significantly lower in comparison to untreated control animals. Infarct size in the area at risk, percent left ventricular necrosis and myocardial tissue preservation were not significantly different in treated and untreated animals. These results suggests that N-acetylcysteine infusion at the time of reperfusion following 90 min of ischemia and 4 h of reperfusion fails to offer significant cardioprotection against free radical damage but it can improve ventricular performance by decreasing pre load.