Pieper G M, Gross G J
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Circulation. 1987 Oct;76(4):916-28. doi: 10.1161/01.cir.76.4.916.
The effects of two antianginal drugs, nicorandil and isosorbide dinitrate (ISDN), on metabolism and function of the ischemic myocardium were studied in a preparation of multiple coronary occlusions in barbital-anesthetized dogs. The preparation consisted of three 5 min occlusions of the left anterior descending coronary artery interspersed by 30 min of reperfusion. An equihypotensive dose of nicorandil (7.5 micrograms/kg/min) or ISDN (12.5 micrograms/kg/min) was infused 15 min before and during the second occlusion period. Hemodynamics, myocardial segment shortening (%SS), tissue blood flow, and myocardial oxygen consumption were determined throughout. Uptake of free fatty acids (FFA), glucose, and lactate were determined during control and ischemic periods. At the end of the final 30 min reperfusion period, biopsy samples of transmural tissue were taken for analysis of phosphocreatine, adenine nucleotides, and total tissue water content. No major hemodynamic changes were produced by either drug except for a 5 to 10 mm Hg decrease in mean aortic pressure. Compared with untreated and ISDN-treated hearts, hearts of dogs treated with nicorandil exhibited reversal of a significant increase in FFA uptake during recurrent ischemia. This was accompanied by an attenuation of the increase in oxygen extraction and CO2 production in the ischemic zone by nicorandil, but not by ISDN. Nicorandil, but not ISDN, improved %SS during reperfusion. Endocardial ATP and total adenine nucleotides were preserved in both nicorandil- and ISDN-treated hearts. Tissue edema was also attenuated by both compounds. Thus, nicorandil improved both function and metabolism during recurrent myocardial ischemia independent of a hemodynamic effect, whereas ISDN only attenuated the loss of adenine nucleotides and increase in tissue water.
在巴比妥麻醉的犬多支冠状动脉闭塞模型中，研究了两种抗心绞痛药物尼可地尔和硝酸异山梨酯（ISDN）对缺血心肌代谢和功能的影响。该模型包括左前降支冠状动脉三次5分钟闭塞，期间穿插30分钟再灌注。在第二次闭塞期前15分钟及闭塞期间，输注等降压剂量的尼可地尔（7.5微克/千克/分钟）或ISDN（12.5微克/千克/分钟）。全程测定血流动力学、心肌节段缩短率（%SS）、组织血流量和心肌耗氧量。在对照期和缺血期测定游离脂肪酸（FFA）、葡萄糖和乳酸的摄取。在最后30分钟再灌注期末，取透壁组织活检样本分析磷酸肌酸、腺嘌呤核苷酸和组织总含水量。除平均主动脉压下降5至10毫米汞柱外，两种药物均未引起重大血流动力学变化。与未治疗和ISDN治疗的心脏相比，尼可地尔治疗的犬心脏在反复缺血期间FFA摄取显著增加的情况出现逆转。这伴随着尼可地尔使缺血区氧摄取和二氧化碳产生的增加减弱，但ISDN无此作用。尼可地尔而非ISDN改善了再灌注期间的%SS。尼可地尔和ISDN治疗的心脏内心肌ATP和总腺嘌呤核苷酸均得以保留。两种化合物均减轻了组织水肿。因此，尼可地尔在反复心肌缺血期间独立于血流动力学效应改善了功能和代谢，而ISDN仅减轻了腺嘌呤核苷酸的丢失和组织水分的增加。
