Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, People's Republic of China.
Basic Res Cardiol. 2011 May;106(3):329-42. doi: 10.1007/s00395-011-0159-y. Epub 2011 Feb 7.
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.
间歇性低氧预处理（IHH）可保护心脏免受缺血性损伤。然而，关于 IHH 对心肌梗死（MI）的治疗效果知之甚少。本研究旨在检验 IHH 治疗是否会影响 MI 后的梗死面积和心脏功能。假手术或左前降支结扎 7 天后，雄性 Sprague-Dawley 大鼠随机暴露于常氧或每天 1 次的 IHH（5000 米）中 14 或 28 天。超声心动图分析显示，与 MI-常氧组相比，14 或 28 天治疗后，IHH 可显著减轻左心室（LV）扩张并改善心脏功能。在分离的 MI- IHH 心脏中进一步证实了 LV 功能的改善。这种保护作用与梗死面积、心肌纤维化和凋亡性心肌细胞的减少有关。与对照组相比，IHH 治疗还增强了 sham 和 MI 组的冠状动脉流量和热休克蛋白 27 的磷酸化。此外，与 sham-IHH 和 MI-常氧组相比，IHH 治疗增加了梗死周边区的毛细血管密度和血管内皮生长因子表达。我们的数据首次表明，IHH 治疗通过减轻进行性心肌重构和改善心肌收缩力对 MI 具有治疗作用。IHH 治疗可能为缺血性心脏病提供一种独特且有前景的治疗方法。
