Therapeutic effect of intermittent hypobaric hypoxia on myocardial infarction in rats

Abstract

Intermittent hypobaric hypoxia (IHH) preconditioning protects the heart against ischemic injuries. However, little is known about the therapeutic effect of IHH on myocardial infarction (MI). The aim of this study was to test whether IHH treatment influences infarct size and cardiac performance after MI. Seven days after sham operation or left anterior descending coronary artery ligation, male Sprague-Dawley rats were randomly exposed to normoxia or one 6-h period each day of IHH (5,000 m) for 14 and 28 days. Echocardiography analysis showed that IHH significantly reduced left ventricular (LV) dilation and improved cardiac performance after 14- or 28-day treatment compared with MI-normoxic groups. The improvement of LV function was further confirmed in isolated perfused MI-IHH hearts. Such protection was associated with attenuated infarct size, myocardial fibrosis, and apoptotic cardiomyocytes. IHH treatment also enhanced coronary flow and phosphorylation of heat shock protein 27 in both sham and MI groups compared with the control groups. In addition, IHH increased the capillary density and vascular endothelial growth factor expression in peri-infarcted zones compared with sham-IHH and MI-normoxic groups. Our data demonstrated for the first time that IHH treatment exerts a therapeutic effect on MI by attenuating progressive myocardial remodeling and improving myocardial contractility. IHH treatment might provide a unique and promising therapeutic approach for ischemic heart diseases.