Higuchi M
J Pharmacol Exp Ther. 1982 Sep;222(3):694-8.
Effects of nitroglycerin on hemodynamics and transmural distribution of myocardial metabolites were studied at 40% of control coronary perfusion pressure induced by acute coronary stenosis in the canine heart. At 40% of coronary perfusion pressure, high energy phosphate (ATP, creatine phosphate) contents significantly diminished in all layers, especially in the inner layer. A 0.3 micrograms/kg/min intracoronary infusion of nitroglycerin showed no direct effects on energy metabolism in the underperfused myocardium. A 3 micrograms/kg/min i.v. administration of the drug under fixed coronary constriction resulted in decrease in left ventricular peak systolic pressure and systemic blood pressure, and further decrease in coronary perfusion pressure and coronary blood flow. Left ventricular end diastolic pressure and ST-segment of the epicardial ECG were elevated. High-energy phosphate contents further decreased while inorganic phosphate and lactate showed an increase. Under these conditions, release of the constriction sufficient for retention of the coronary perfusion pressure at about 40 mm Hg resulted in significant improvement of the myocardial energy metabolism without a further increase in coronary blood flow. The results suggest that when the myocardium is underperfused due to undilatable stenotic vessels with maximum autoregulation of the regional flow, it may be dangerous to administer nitroglycerin in a dose sufficient to produce a large decrease in coronary perfusion pressure.
在犬心脏急性冠状动脉狭窄诱导的对照冠状动脉灌注压的40%条件下,研究了硝酸甘油对血流动力学和心肌代谢产物跨壁分布的影响。在冠状动脉灌注压为40%时,所有层的高能磷酸(ATP、磷酸肌酸)含量均显著降低,尤其是内层。冠状动脉内输注硝酸甘油0.3微克/千克/分钟对灌注不足的心肌能量代谢无直接影响。在固定冠状动脉收缩的情况下,静脉注射该药物3微克/千克/分钟导致左心室收缩压峰值和全身血压降低,冠状动脉灌注压和冠状动脉血流量进一步降低。心外膜心电图的左心室舒张末期压力和ST段升高。高能磷酸含量进一步降低,而无机磷酸盐和乳酸则增加。在这些条件下,解除收缩以使冠状动脉灌注压维持在约40 mmHg足以显著改善心肌能量代谢,而冠状动脉血流量没有进一步增加。结果表明,当心肌因不可扩张的狭窄血管而灌注不足且区域血流最大程度自动调节时,给予足以使冠状动脉灌注压大幅降低的剂量的硝酸甘油可能是危险的。