Ischemia-induced remodeling of the heart : macro- and micro-systems approach to heart function

点击翻译按钮获取中文摘要

Cardiac ischemia results in the increased vulnerability to lethal arrhythmias such as ventricular tachycardia and fibrillation. Cardiac ischemia also produces the death of cardiac myocytes by either necrosis or apoptosis. The present study aims at elucidating the mechanisms responsible for remodeling in the post-infarcted heart, and for conversion between ventricular tachycardia(VT) and fibrillation(VF). The results are summarized as follows :1. Ligation of the left coronary artery of rat hearts resulted in the acute death of ventricular cardiac myocytes. Post-infarction left ventricular remodeling occurred at 2-3 weeks after the coronary artery ligation. TUNEL staining or immunohistochemical analysis using an anti-activated caspase-3 antibody revealed that apoptotic death of myocytes was observed almost coinciding with the morphological changes of the heart, suggesting that apoptosis of cardiac myocytes contributed to the process of post-infarction left ventricular remodeling.2. In Langendorff-perfused rat hearts, treatment with either L-NMMA, an inhibitor of nitric oxide synthase (NOS), or 5-HD, a specific blocker of mitochondrial ATP-sensitive potassium (mitoK__<ATP>) channels, during reperfusion attenuated the vulnerability to ischemia/reperfusion-induced VT/VF, suggesting that the increased production of nitric oxide (NO) and the resultant activation of mitoK__<ATP> channels during reperfusion were involved in the increased vulnerability to ischemia/reperfusion-induced VT/VF.3. In Langendorff-perfused rat hearts, perfusion with either ruthenium red (RR) or Ru 360, blockers of calcium uptake by mitochondria, resulted in the reversible conversion of VF to VT. Perfusion with spermine, an activator of mitochondrial calcium uptake, produced reversible conversion of VT to VF. These results suggested that changes in the calcium uptake by mitochondria contributed to the macro-dynamical transition between VT and VF.