Tacrolimus ameliorates functional disturbances and oxidative stress in isoproterenol-induced myocardial infarction

Abstract

Background: The inflammatory responses play a major role in the pathogenesis of acute myocardial infarction (MI). Early inhibition of inflammation may improve post MI cardiac function. The aim of this study was to investigate the effects of tacrolimus on cardiac function, hemodynamic parameters as well as histopathologic and electrocardiographic changes in isoproterenol-induced myocardial infarction. Methods: Male Wistar rats were randomly divided into six groups of control, isoproterenol alone, tacrolimus alone, and isoproterenol plus tacrolimus (0.5, 1 and 2 mg/kg). Isoproterenol (100 mg/kg) was injected subcutaneously for two consecutive days to induce myocardial infarction, and simultaneously tacrolimus was administered orally twice a day for three days. Results and conclusions: Administration of isoproterenol resulted in myocardial edema and necrosis as well as a marked reduction in the left ventricular systolic pressure (LVSP), left ventricular contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)) along with a severe elevation in left ventricular end-diastolic pressure (LVEDP). Isoproterenol also elevated the ST-segment and suppressed the R-amplitude and R-R interval on ECG. It was found that all doses of tacrolimus could amend the ECG pattern and ameliorated the isoproterenol induced disturbances in cardiac function. Acute and short term treatment with tacrolimus at dose of 2 mg/kg significantly (P < 0.001) improved LVdP/dt(max) from 2712 +/- 82 in myocardial infarcted rats to 4592 +/- 149 mmHg/sec. Similarly, tacrolimus lowered LVEDP from 17.6 +/- 0.68 in MI group to the value of 5.6 +/- 0.22 mmHg (P < 0.001). Furthermore, tacrolimus was found to reduce malondialdehyde concentration in serum and myocardium by 50-70% (P < 0.001). The results of this study showed that acute treatment with tacrolimus, coincided with the occurrence of myocardial infarction, strongly protected the myocardium against the isoproterenol-induced myocardial infarction; where this might be due to the anti-inflammatory properties of tacrolimus.