Strategies for Treatment of Myocardial Infarction: Experimental and Clinical Studies

Abstract

Aim and Objective: To test the hypothesis that tamoxifen is cardio protective and prevents the transition of myocardial infarction to heart failure. Methods: In Isoproterenol induced myocardial infarction, isoproterenol (100 mg/kg/day, i.p.) was administered for 2 days in health adult SD rats of either sex. Along with that control group received normal saline and treated group received Tamoxifen (2 mg/kg/day, p.o.) for 14 days. After 14 days animals were sacrificed and various biochemical and cardiac parameters were evaluated. Parameter evaluated were serum lipid profile, cardiac markers like Creatinine kinase-MB, Lactate dehydrogenase, C reactive protein, hypertrophic parameters like cardiac hypertrophy index, Left ventricular hypertrophic (LV) index, LV weight/ Right ventricle weight, LV wall thickness, Infarct size determinations like infarct area and LV cavity area, hemodynamic parameters, LV collagen and Na+ K+ ATPase activity, pro-oxidant, antioxidant levels and morphometric parameters like Cardiomyocyte diameter, Cardiomyocyte length and Cardiomyocyte area. Results: Isoproterenol control rats showed a significant increase in the levels of total cholesterol, serum LDL, serum VLDL and triglyceride and while a significant decrease in HDL levels was observed. Treatment with tamoxifen (2 mg/kg/day, p.o.) significantly reduced serum total cholesterol, serum LDL, serum VLDL and triglycerides levels in isoproterenol treated rats. Also, there was a significant increase in serum cardiac markers like Lactate dehydrogenase (LDH) and Creatinine kinase- MB (CKMB) in isoproterenol control rats. Treatment with tamoxifen significantly reduced serum level of LDH and CKMB in isoproterenol treated rats. Further, isoproterenol control rats exhibited increase levels of C reactive protein (CRP). Treatment with tamoxifen significantly reduced CRP level in isoproterenol treated rats. Moreover, Isoproterenol control rats exhibited significant increase in cardiac hypertrophy index (CHI), Left ventricular (LV) hypertrophic index, left ventricular weight to right ventricular weight ratio and LV thickness. Treatment with tamoxifen significantly reduced CHI, LV hypertrophic index, right ventricular weight ratio and LV thickness in isoproterenol treated rats. A marked increase myocardial infarct area and LV cavity area was observed in isoproterenol control rats. Treatment with tamoxifen significantly decreased the % area of infarction and LV cavity area. Also, isoproterenol control rats showed increase LV collagen level and decreased Na+ K+ ATPase activity. Treatment with tamoxifen significantly reduced LV collagen levels and increased Na+ K+ ATPase activity in isoproterenol treated rats. Isoproterenol control rats exhibited significant increase in blood pressure and heart rate. Treatment with tamoxifen produced significant change in blood pressure and heart rate. Further, isoproterenol control rats showed increase pro oxidant level i.e malondialdehyde (MDA) and reduced antioxidant levels such as superoxide dismutase (SOD) and reduced glutathione (GSH) levels. Treatment with tamoxifen significantly reduced MDA levels and increased SOD and GSH levels in isoproterenol treated rats. Reduction in myocardial infarction with treatment of tamoxifen in isoproterenol treated rats was further supported by histopathological studies of left ventricle, which shows marked reduction in fibrosis and increase extracellular space as compare to Isoproterenol control rats. Conclusions: From, above findings we have concluded tamoxifen produces beneficial effects in myocardial infarction and thus prevents its transition to heart failure.