The mechanism of inhibitory effects of antiischemic drugs on calcium paradox.

点击翻译按钮获取中文摘要

The purpose of the present study was to know the mechanism of cell injury induced by calcium paradox,and to obtain new information for inhibition of myocardial cell injury induced by ischemia. Four different experiments were performed.1.In isolated rat cardiac myocytes,the intracellular calcium concentration ([Ca^<2+>]i) decreased during calcium- free perfusion, but the [Ca^<2+>]i increased and exceeded the normal value after calcium-repletion. dl-Propranolol inhibited the increase of [Ca^<2+>]i.2.Changes in developed tension and [Ca^<2+>]i during calcium-free perfusion and calcium-repletion were measured in electrically stimulated rat left atria. During calcium-free perfusion,developed tension and systolic [Ca^<2+>]i decreased,but diastolic [Ca^<2+>]i increased. Calcium-repletion increased the developed tension and diastolic [Ca^<2+>]i. Thus,the change in developed tension was not always parallel to the change of [Ca^<2+>]i. dl-Propranolol inhibited the increase of diastolic [Ca^<2+>]i during calcium-free perfusion.3.The effects of antiischemic drugs on cell injury induced by veratridine based on sodium- and calcium- overload were examined in isolated rat cardiac myocytes. In addition to dl-propranolol and l-penbutolol,d- propranolol and d-penbutolol inhibited the cell injury. The result suggests that sodium channel blocking action plays an important role in inhibiting of the cell injury induced by veratridine.4.The effect of-d-propranolol on post-ischemic reperfusion injury was examined in isolated perfused rat hearts. d-Propranolol accelerated the recovery of cardiac function during reperfusion.The drug also attenuated the decrease of tissue ATP content during ischemia and inhibited the accumulation of non-esterified fatty acid during reperfusion. From these results,it is suggested that sodium channel blocking action plays an important role in protective effects of antiischemic drugs from the cell injury induced by calcium paradox and ischemia.