Chronic Administration of Catestatin Improves Autonomic Function and Exerts Cardioprotective Effects in Myocardial Infarction Rats.

Abstract

Catestatin (CST), which is emerging as a novel cardiac modulator, can protect the heart against excessive sympathetic drive in hypertensive cardiomyopathy. The aim of this study is to investigate whether exogenous CST decreases excessive cardiac sympathetic drive and improves autonomic function and exerts cardioprotective effects in myocardial infarction (MI) rats. Rats were divided into a sham group, MI group, and MI plus CST (MI + CST) group. Four weeks later, the autonomic function of the animals was assessed by analyzing heart rate variability (HRV) and measuring plasma catecholamine. Cardiac function was evaluated via echocardiography. Electrophysiological characteristics were assessed in Langendorff-perfused hearts. Compared to the MI group, the chronic administration of CST significantly increased the standard deviation of normal-normal intervals (P < .01) and low-frequency (LF) and high-frequency (HF) HRV and decreased the ratio of LF-HF HRV (P < .01 for all). Additionally, the level of plasma catecholamine was reduced in the MI + CST group compared to the MI group (P < .01). Treatment with CST significantly increased ejection fraction (EF) and fraction shorting (FS) and significantly decreased the left ventricular end-systolic diameter and left ventricular end-diastolic diameter at 28 days postmyocardial infraction (P < .05 for all). After MI, the ventricular repolarization duration, such as QTc intervals and action potential duration (APD) at 90% repolarization, was prolonged, and this prolongation could be decreased by CST (P < .05 for all). The CST also increased the threshold of ADP alternans (P < .01). Moreover, ventricular arrhythmias were induced in 83% of the MI group but only 33% of the MI + CST group (P < .05). These results suggested that the chronic administration of CST plays a role in cardioprotection in MI rats, which may function by decreasing the cardiac sympathetic drive and improving autonomic function.