Ichihara K, Abiko Y
J Pharmacol Exp Ther. 1982 Sep;222(3):720-5.
The effect of diltiazem on ischemic myocardial acidosis was studied in the canine heart whose left anterior descending coronary artery was partially occluded to reduce coronary flow to about one-third (partial occlusion). Myocardial pH was measured by use of a micro glass pH electrode. The pH decreased from 7.53 to 6.93 by partial occlusion and appeared to reach a steady state within 30 min. Saline or drugs were injected i.v. 30 min after partial occlusion. The decreased pH increased spontaneously by 34% of the total reduction of pH in the next 60 min after saline injection. Diltiazem (100 micrograms/kg) potentiated the increase in pH; the pH increased by 76% 60 min after the injection. Propranolol (1 mg/kg) also potentiated the increase in pH that had been decreased by partial occlusion. The relation between pH decrease and the tissue levels of metabolites was also studied. The reduction of myocardial pH from 7.5 to 6.8 was accompanied by a 2-fold increase in the tissue lactate content and by decreases in the ATP and creatine phosphate contents. There was a significant correlation between the hydrogen ion concentration calculated from the pH and each of the lactate, ATP and creatine phosphate contents. The present study indicates that diltiazem attenuates ischemic myocardial acidosis.
在犬心脏上研究了地尔硫䓬对缺血性心肌酸中毒的影响。通过部分闭塞左冠状动脉前降支使冠脉血流量减少至大约三分之一(部分闭塞)。使用微型玻璃pH电极测量心肌pH值。部分闭塞使pH值从7.53降至6.93,并在30分钟内似乎达到稳定状态。部分闭塞30分钟后静脉注射生理盐水或药物。注射生理盐水后,降低的pH值在接下来60分钟内自发升高,升高幅度为pH值总降低幅度的34%。地尔硫䓬(100微克/千克)增强了pH值的升高;注射后60分钟pH值升高了76%。普萘洛尔(1毫克/千克)也增强了因部分闭塞而降低的pH值的升高。还研究了pH值降低与代谢物组织水平之间的关系。心肌pH值从7.5降至6.8伴随着组织乳酸含量增加2倍以及ATP和磷酸肌酸含量降低。根据pH值计算的氢离子浓度与乳酸、ATP和磷酸肌酸含量中的每一项之间均存在显著相关性。本研究表明地尔硫䓬可减轻缺血性心肌酸中毒。