Sakai K, Ichihara K, Nasa Y, Kamigaki M, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Arch Int Pharmacodyn Ther. 1990 Sep-Oct;307:92-108.
The present study was undertaken to examine whether dichloroacetate, which inhibits pyruvate dehydrogenase kinase and, therefore, increases the activity of pyruvate dehydrogenase, attenuates myocardial acidosis and metabolic changes induced by coronary occlusion. In dogs anesthetized with pentobarbital, the left anterior descending coronary artery was incompletely occluded to reduce the left anterior descending flow to a half to one third of the original flow (partial occlusion) to produce myocardial (regional) ischemia. Partial occlusion was continued for 90 min, and a bolus injection of saline or dichloroacetate was made intravenously 30 min after the onset of occlusion. Partial occlusion decreased myocardial pH significantly. An injection of dichloroacetate (150 mg/kg) increased myocardial pH that had been lowered by partial occlusion. Myocardial metabolites were measured in other dogs. Partial occlusion decreased the myocardial levels of adenosine triphosphate, creatine phosphate and energy charge potential, and increased that of lactate significantly, without affecting the myocardial levels of pyruvate and nonesterified fatty acids. Dichloroacetate attenuated the ischemia-induced changes in the myocardial levels of adenosine triphosphate, creatine phosphate, energy charge potential and lactate. These results indicate that dichloroacetate attenuates the myocardial acidosis and metabolic changes during coronary partial occlusion.
本研究旨在探讨二氯乙酸是否能减轻冠状动脉闭塞所致的心肌酸中毒和代谢变化。二氯乙酸可抑制丙酮酸脱氢酶激酶，从而增加丙酮酸脱氢酶的活性。在戊巴比妥麻醉的犬中，不完全闭塞左前降支冠状动脉，使左前降支血流减少至原血流的一半至三分之一（部分闭塞），以产生心肌（局部）缺血。部分闭塞持续90分钟，闭塞开始30分钟后静脉推注生理盐水或二氯乙酸。部分闭塞显著降低心肌pH值。注射二氯乙酸（150mg/kg）可使因部分闭塞而降低的心肌pH值升高。在其他犬中测量心肌代谢物。部分闭塞降低了心肌三磷酸腺苷、磷酸肌酸和能量负荷电位的水平，并显著增加了乳酸水平，而不影响心肌丙酮酸和非酯化脂肪酸的水平。二氯乙酸减轻了缺血引起的心肌三磷酸腺苷、磷酸肌酸、能量负荷电位和乳酸水平的变化。这些结果表明，二氯乙酸可减轻冠状动脉部分闭塞期间的心肌酸中毒和代谢变化。
