The inhibitory effect of rosmarinic acid on overexpression of NCX1 and stretch-induced arrhythmias after acute myocardial infarction in rats

The incidence of arrhythmias is the main cause of high mortality after myocardial infarction (AMI). The aim of the present study was to determine whether the rosmarinic acid (RA) could reduce the stretch-induced arrhythmias (SIAs) related to overexpression of NCX1 after AMI. Adult male Sprague-Dawley rats were randomly allocated into six groups: Sham, MI (100 mg/kg of isoproterenol (Iso), subcutaneously, on two consecutive days), RA (30 mg/kg, orally, 14 days), and RA (10, 15 and 30 mg/kg, 14 days) + I. MI induction was performed on the 13th and 14th days of the study period. Forty-eight hours after the first injection of Iso, the parameters of hypertrophy, plasma levels of malondialdehyde (MDA) and lipid profile were evaluated. Using Langendorff apparatus, the isolated hearts were transiently stretched for 5 s with three different end-diastolic volumes (Delta V-1to3 = 0.05, 0.1 and 0.2 mL). Cardiac function parameters were measured for 30 s, and ventricular arrhythmias were recorded for 3 min after each stretch. Finally, the levels of cardiac troponin-I and NCX1 mRNA expression were examined. The rats of MI group showed a significant increase in hypertrophy index, MDA, triglyceride and cholesterol (P < 0.001). Additionally, a marked impairment in cardiac parameters, an increase in the rates of SIAs and NCX1 expression, and a decrease in troponin-I (P < 0.001) were observed. RA at three doses especially 15 mg/kg strongly improved almost all the mentioned factors (P < 0.001). Our results confirm that RA pretreatment could prevent hypertrophia, arrhythmia and cardiac dysfunction following AMI which is associated with inhibition of lipid peroxidation and overexpression of NCX1.