Late cardiac perconditioning by phenylephrine in an isolated rat heart model is mediated by mitochondrial potassium channels

The present study was designed to investigate the effect of early and late administration of phenylephrine during ischemia against regional ischemia-reperfusion injuries in an isolated rat heart model. All animals were randomly divided into experimental groups: (I) IR (Ischemic/ reperfusion): the hearts underwent 35 min of regional ischemia followed by 60 min of reperfusion; (II) 5HD-IR-0: the hearts were perfused for 5 min with 5HD (5-hydroxydecanoate, specific mKATP channel blocker, 100 µM) at the onset of regional ischemia; (III) 5HD-IR-20: the hearts were perfused for 5 min with 5HD 20 min after regional ischemia; (IV) PE-IR-10: the hearts were perfused for 5 min with phenylephrine 10 min after regional ischemia; (V) PE-IR-30: the hearts were perfused for 5 min with phenylephrine (100 µM) 30 min after regional ischemia; (VI) PE-5HD-IR-10 group: the hearts were perfused for 5 min with 5HD at the onset of regional ischemia after which phenylephrine was administrated as in group IV; and (VII) PE-5HD-IR-30: the hearts were perfused for 5 min with 5HD 20 min after the ischemia and then phenylephrine was administrated as in group V. The hemodynamic parameters were recorded throughout the experiment. Ischemia-induced arrhythmias, myocardial infarct size (IS), creatin kinase-MB isoenzyme (CK-MB), plasma lactate dehydrogenase (LDH) activities, and coronary blood flow (CBF) were measured in all animals. Perfusion of phenylephrine 30 min after the regional ischemia curtailed the myocardial infarct size, reduced CK-MB, and improved cardiac function and CBF. Administration of 5HD 30 min after the ischemia abolished cardioprotective effects of phenylephrine in the late phase. These results suggest the involvement of mKATP in the mechanism of phenylephrine-induced late preconditioning.

Effects of exercise combined with apelin-13 on cardiac function in the isolated rat heart / Efeitos do exercício combinado com apelina-13 na função cardíaca no coração isolado de ratos / Efectos del ejercicio combinado con apelin-13 en la función cardiaca del corazón de ratones aislados

ABSTRACT Exercise and apelin have been shown to increase cardiac function and elicit tolerance to ischemia/reperfusion (IR) injuries. This study aimed at determining whether the combination of exercise training and apelin pretreatment could integrate the protective effects of each of them in the heart against IR injury. Male rats were divided into four experimental groups: 1: Rats with ischemia/reperfusion (IR), 2: subjected to exercise training for 8 weeks (EX+IR), 3: apelin-13 (10 nmol/kg/day) for 7 days (Apel+IR) in the last week of training, and 4: exercise training plus apelin-13 (EX+Apel+IR). Isolated hearts were perfused using the Langendorff method and subjected to 30 min of regional ischemia followed by 60 min of reperfusion. Treadmill exercise training was conducted for 8 weeks. Hemodynamic parameters were recorded throughout the experiment. Ischemia-induced arrhythmias, myocardial infarct size (IS), creatine kinase-MB (CK-MB) isoenzyme and plasma lactate dehydrogenase (LDH) activity was measured in all animals. Administration of apelin-13 plus exercise increased left ventricular developed pressure (LVDP) at the end of ischemia and reperfusion compared with other groups. After 30 min of ischemia, dP/dtmax was higher in EX+Apel+IR than in Apel+IR and EX+IR groups. During 30 min ischemia, exercise training, apelin-13 and combined treatment produced a significant reduction in the numbers of premature ventricular complexes. A combination of exercise and apelin-13 also reduced infarct size, CK-MB, LDH and severity of arrhythmia. These results suggest that combined therapies with apelin-13 and exercise training may integrate the beneficial effects of each of them alone on cardiac contractility, arrhythmia and limiting of infarct size. Level of evidence I; Therapeutic Studies - Investigating the Results of Treatment.

RESUMO Foi demonstrado que o exercício e a apelina aumentam a função cardíaca e induzem a tolerância à lesões por isquemia/reperfusão (IR). O objetivo do presente estudo foi determinar se a combinação de treinamento físico e pré-tratamento com apelidos poderia integrar os efeitos protetores de cada um deles no coração contra a lesão por IR. Ratos machos foram divididos em quatro grupos experimentais: 1- Ratos com isquemia/ reperfusão (IR), 2- submetidos ao treinamento físico por 8 semanas (EX + IR), 3- apelino-13 (10 nmol / kg / dia) por 7 dias (Apel + IR) na última semana de treinamento, 4- treinamento físico mais apelina-13 (EX + Apel + IR). Corações isolados foram perfundidos pelo método de Langendorff e submetidos à 30 min de isquemia regional, seguida de 60 min de reperfusão. Treino em esteira foi conduzido por 8 semanas. Parâmetros hemodinâmicos foram registrados ao longo do experimento. Arritmias induzidas por isquemia, tamanho do infarto do miocárdio (IS), atividade da isoenzima Creatina Cinase-MB (CK-MB) e lactato desidrogenase plasmática (LDH) foram medidos em todos os animais. A administração de apelin-13 mais exercício aumentou a pressão desenvolvida pelo ventrículo esquerdo (LVDP) no final da isquemia e reperfusão em comparação com outros grupos. Após 30 min de isquemia, dp / dtmax foi maior em EX + Apel + IR do que nos grupos Apel + IR e EX + IR. Durante 30 min isquemia, treinamento físico, apelina-13 e tratamento combinado produziram redução significativa no número de complexos ventriculares prematuros. Combinação de exercício e apelina-13 também reduziu o tamanho do infarto, CK-MB, LDH e gravidade da arritmia. Estes resultados sugerem que terapias combinadas com apelina-13 e treinamento físico podem integrar os efeitos benéficos de cada um deles sozinhos na contratilidade cardíaca, arritmia e limitação do tamanho do infarto. Nível de evidência I; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Se ha demostrado que el ejercicio y la apelina aumentan la función cardíaca y provocan tolerancia a las lesiones por isquemia/reperfusión (IR). Los objetivos del presente estudio fueron determinar si la combinación de entrenamiento con ejercicio y pre-tratamiento con apelina podrían integrar los efectos protectores de cada uno de ellos en el corazón frente a la lesión por IR. Los ratones machos se dividieron en cuatro grupos experimentales: 1: ratones con isquemia/reperfusión (IR) 2: sometidos a entrenamiento durante 8 semanas (EX + IR), 3: apelina-13 (10 nmol / kg / día) durante 7 días (Apel + IR) en la última semana de entrenamiento 4: entrenamiento físico más apelina-13 (EX + Apel + IR). Los corazones aislados se perfundieron mediante el método de Langendorff y se sometieron a 30 minutos de isquemia regional, seguidos de 60 minutos de reperfusión. El entrenamiento de la cinta de correr se llevó a cabo durante 8 semanas. Los parámetros hemodinámicos se registraron a lo largo del experimento. Se midieron las arritmias inducidas por isquemia, el tamaño del infarto de miocardio (IS), la isoenzima Creatina Kinase-MB (CK-MB) y las actividades de lactato deshidrogenasa plasmática (LDH) en todos los animales. La administración de ejercicios de apelina-13 plus aumenta la presión desarrollada del ventrículo izquierdo (PDVI) al final de la isquemia y la reperfusión en comparación con otros grupos. Después de 30 min de isquemia, la dp/dt max fue más alta en EX + Apel + IR que en los grupos Apel + IR y EX + IR. Durante la isquemia de 30 minutos, el entrenamiento físico, la apelina-13 y el tratamiento combinado, produjeron una reducción significativa en el número de complejos ventriculares prematuros. La combinación de ejercicio y apelina-13 también redujo el tamaño del infarto, CK-MB, LDH y la gravedad de la arritmia. Estos resultados sugieren que las terapias combinadas con apelina-13 y el entrenamiento físico pueden integrar los efectos beneficiosos de cada uno de ellos solo sobre la contractilidad cardíaca, la arritmia y la limitación del tamaño del infarto. Nivel de Evidencia I; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Aerobic training and L-arginine supplement attenuates myocardial infarction-induced kidney and liver injury in rats via reduced oxidative stress

Introduction The aim of the present study was to determine the effect of exercise training and l-arginine supplementation on kidney and liver injury in rats with myocardial infarction (MI). Material and methods Four weeks after MI, 50 male wistar rats randomly divided into five followed groups: sham surgery without MI (Sham, n = 10), Sedentary-MI (Sed-MI, n = 10) 3: L-Arginine-MI (La-MI, n = 10) 4: Exercise training-MI (Ex-MI, n = 10) and 5: Exercise and L-arginine-MI (Ex + La-MI). Ex-MI and Ex + La-MI groups running on a treadmill for 10 weeks with moderate intensity. Rats in the L-arginine-treated groups drank water containing 4% L-arginine. Tissues oxidative stress and kidney and liver functional indices were measured after treatments. Result Urea as a kidney function indexes, increased in Sed-MI group in compared to sham group and decreased significantly in Ex-MI and Ex + La-MI groups. The level of catalase (CAT) and glutathione stimulating hormone (GSH) of kidney were significantly lower in the MI-groups compared with the Sham group and kidney Malondialdehyde (MDA) levels increased after MI and significantly decreased in response to aerobic training and L-arginine. As well as, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as liver injury indices, increased in MI-groups and decreased by training and L-arginine. In this regards, liver MDA and CAT respectively increased and decreased in MI-groups, but aerobic training and L-arginine increased liver glutathione per-oxidase (GPx) and decreased liver MDA. Conclusion These results demonstrated that kidney and liver function impaired 14 weeks after MI and aerobic training and L-arginine supplementation synergistically ameliorated kidneys and liver injury in myocardial infarction rats through oxidative stress reduction.