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

本研究旨在了解钙悖论引起心肌细胞损伤的机制，为抑制心肌缺血引起的细胞损伤提供新的信息。进行了四种不同的实验。在离体大鼠心肌细胞中，无钙灌注时细胞内钙浓度（[Ca^<2+>]i）降低，而充钙后细胞内钙浓度（[Ca^<2+>]i）升高并超过正常值。心得安抑制[Ca^<2+>]i. 1的升高。测定电刺激大鼠左心房无钙灌注和充钙时的张力和[Ca^<2+>]i的变化。无钙灌注时，出现的张力和收缩期[Ca^<2+>]i降低，舒张期[Ca^<2+>]i升高。钙补充增加了已发展的张力和舒张[Ca^<2+>]i。因此，展开张力的变化并不总是平行于[Ca^<2+>]i的变化。2 .普萘洛尔抑制无钙灌注时舒张[Ca^<2+>]i升高。在离体大鼠心肌细胞中，观察了抗缺血药物对缬曲定钠、钙过载诱导的细胞损伤的影响。除-心得安和-心得安外，-心得安和-心得安对细胞损伤有抑制作用。结果表明，钠通道阻断作用在抑制缬草碱诱导的细胞损伤中起重要作用。研究了d-心得安对大鼠离体心脏缺血再灌注损伤的影响。d-心得安可加速心功能再灌注恢复。该药还能减轻缺血时组织ATP含量的下降，抑制再灌注时非酯化脂肪酸的积累。上述结果提示，钠通道阻断作用在抗缺血药物对钙悖论和缺血引起的细胞损伤的保护作用中起重要作用。

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.