Kirkels J H, Ruigrok T J, van Echteld C J, Ceconi C, Ferrari R
Interuniversity Cardiology Institute, The Netherlands.
Cardioscience. 1992 Mar;3(1):27-34.
Rats were given anipamil (5 mg/kg) or glucose, intraperitoneally twice daily for 5 days. During this period the mean arterial blood pressure and heart rate were measured daily. The heart was then isolated and perfused. Energy metabolism and intracellular pH were monitored by 31P nuclear magnetic resonance spectroscopy during 30 minutes of ischemia followed by 30 minutes of reperfusion, with a simultaneous isovolumetric measurement of left ventricular contraction. Myocardial norepinephrine and glycogen were assayed immediately after excision of the heart, after 15 minutes oxygenated perfusion, at the end of ischemia and at the end of reperfusion. Metabolic and functional recovery during reperfusion were significantly better in hearts pretreated with anipamil (p less than 0.0005 vs controls). However, protection was not preceded by an effect on mean arterial pressure or heart rate in vivo, or a negative inotropic effect during control perfusion of the isolated hearts. There was no energy sparing effect during ischemia; but intracellular pH during ischemia stabilized at a higher level (p less than 0.0005 vs controls). Myocardial norepinephrine and glycogen stores were not decreased by pretreatment with anipamil, and their release or degradation due to ischemia and reperfusion were also not different from controls. Commonly known mechanisms of myocardial protection by calcium antagonists fail to explain the protection by pretreatment with anipamil as observed in our experiments, and alternative mechanisms are to be considered.
给大鼠腹腔注射阿尼帕米（5毫克/千克）或葡萄糖，每日两次，共5天。在此期间，每天测量平均动脉血压和心率。然后分离心脏并进行灌注。在30分钟缺血后再灌注30分钟期间，通过31P核磁共振波谱监测能量代谢和细胞内pH值，同时对等容状态下的左心室收缩进行测量。在心脏切除后、15分钟充氧灌注后、缺血结束时和再灌注结束时，立即测定心肌去甲肾上腺素和糖原含量。阿尼帕米预处理的心脏在再灌注期间的代谢和功能恢复明显更好（与对照组相比，p<0.0005）。然而，在体内对平均动脉血压或心率没有影响，在离体心脏的对照灌注期间也没有负性肌力作用之前，就已经有了保护作用。缺血期间没有能量节省效应；但缺血期间细胞内pH值稳定在较高水平（与对照组相比，p<0.0005）。阿尼帕米预处理并未降低心肌去甲肾上腺素和糖原储备，其因缺血和再灌注导致的释放或降解与对照组也无差异。钙拮抗剂保护心肌的常见机制无法解释我们实验中观察到的阿尼帕米预处理的保护作用，因此需要考虑其他机制。
