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

抗缺血药物抑制钙悖论的机制。

• 批准号: 03454140
• 负责人: ABIKO Yasushi
• 金额: $ 3.84万
• 依托单位: ASAHIKAWA MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454140/
• 关键词: Intracellular calcium concentration; Cardiac myocytes; Fura-2; Calcium paradox; beta-adrenoceptor blockers; veratridine; ベラトソジン; カルシウムイオン; カルシウム拮抗薬; β‐遮断薬

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.

本研究旨在了解钙离子悖论诱导心肌细胞损伤的机制，为抑制心肌细胞缺血损伤提供新的信息。实验分为四组：1.大鼠心肌细胞无钙灌流时，细胞内钙离子浓度([Ca^&lt；2+&gt；]i)下降，缺钙后[Ca^&lt；2+&gt；]i升高并超过正常值。2.电刺激大鼠左心房，观察无钙灌流和补钙过程中发展张力和[Ca~(2+)]i的变化。在无钙灌流过程中，舒张期[Ca^&lt；2+&gt；]i升高，收缩期[Ca^&lt；2+&gt；]i降低。在无钙灌流过程中，心肌细胞的舒张期[Ca^&lt；2+]i和舒张期[Ca^&lt；2+&gt；]i的变化与舒张期张力和舒张期[Ca^&lt；2+&gt；]i的变化并不是平行的。除dl-心得安和L-戊丁洛尔外，d-心得安和d-戊丁洛尔对细胞损伤也有抑制作用。结果提示，钠通道阻断作用在抑制藜芦碱诱导的细胞损伤中起重要作用。4.观察-d-心得安对大鼠心脏缺血再灌注损伤的影响。D-心得安可加速再灌注期心功能的恢复，并能减轻缺血时组织ATP含量的下降，抑制再灌注期非酯化脂肪酸的积聚。提示钠通道阻断作用在抗缺血药物对钙离子反常和缺血所致细胞损伤的保护作用中起重要作用。