RESUMO
Because myocardial infarction [MI] is a major cause of morbidity and mortality worldwide, protecting and remedy of the heart from the ischemia is the focus of intense research. This study aims to investigate the effects and the possible mechanism of melatonin in isoproterenol [ISO] induced acute MI in rabbits by studying electrocardiography [ECG], its angiogenic role, anti-inflammatory and antioxidants effects as well as histopathological changes of the cardiac muscle. A total of 50 rabbits were randomly divided into 5 groups, each of which were 10 rabbits: [I] Control group: received vehicle only, [II] Melatonin group: received melatonin in a dose of 10 mg/kg by intraperitoneal injection [i.pj, [III] MI group: MI was induced with ISO [85 mg /kg] administered subcutaneously twice at an interval of 24 h. [IV] Prophylactic group: melatonin injection was done for 7 days and induction of infarction with ISO was done at the 6[th] and 7[th] day of the experiment and [V] Therapeutic group: Injected with ISO in the 1[st] and 2[nd] day and melatonin was given for 7 days starting at day one of induced infarction. The following parameters were evaluated: ECG, heart weight/ body weight [HW/BW] ratio, serum levels of cardiac marker enzymes [creatinine kinase-MB [CK-MB], laclate dehydrogenase [LDH] and cardiac troponin-T [cTnT]]., inflammatory markers [serum tumor necrosis factor-a [TNFa] and cardiac myloperoxidase [MPO] enzyme], cardiac total peroxides level, total antioxidant capacity [TAC], oxidative stress index [OSI], angiogenic markers [cardiac vascular endothelial growth factor [VEGF] and inducihle nitric oxide [iNO]], and histopathological changes of the cardiac muscle. ISO induced MI rabbits showed significant pathological changes in the ECG pattern [elevated ST-segment and decreased R amplitude], significant increased HW/BW ratio, significant increased serum levels of cardiac marker enzymes [CK-MB, LDH and cTnT]. Also, inflammatory markers [serum TNF-alpha and cardiac MPO], angiogenic markers [VEGF and iNO], total peroxides and OS I were significantly higher whereas TAC were significantly lower in MI group as compared to control group. The histopathological findings of the myocardial tissue evidenced myocardial damage in ISO induced MI rabbits. Administration of melatonin in prophylactic and therapeutic groups revealed that melatonin has an efficient anti-inflammatory and antioxidant activity, reduced the cardiac marker enzymes and the pathological ECG patterns, ameliorated the increase in the HW/BW ratio and augmented myocardial angiogenesis. Also, decreased myocardial damage was evidenced by the histopathological findings with melatonin administration. The mending effects of melatonin in prophylactic group were more prominent than in the therapeutic group. The present study clearly demonstrated the cardioprotective effects of melatonin in a model of induced myocardial infarction which could be due to its anti-inflammatory, membrane stabilizing and free radical scavenging properties. Interestingly, this study is the first to prove the cardioprotective effect of melatonin via its angiogenic effect. Thereby, it should be considered for prophylactic and as a novel adjunctive therapy for attenuating ischemic myocardial damage