Horowitz J D
Department of Cardiology, Queen Elizabeth Hospital, Woodville, Australia.
Am J Med. 1991 Sep 30;91(3C):113S-117S. doi: 10.1016/0002-9343(91)90293-7.
The development of unstable angina pectoris and acute myocardial infarction is a process of platelet aggregation and thrombus formation associated with local coronary vasoconstriction. Regional deficiencies in endothelial vasodilator function, due to reduced formation of endothelium-derived relaxing factor (EDRF), may predispose to platelet aggregation and coronary vasoconstriction. Nitroglycerin (NTG), frequently utilized in the management of unstable angina pectoris and acute myocardial infarction, undergoes bioconversion, via a sulfhydryl-dependent process, to nitric oxide, which is identical or closely related to EDRF. Other products of the nitrate bioconversion "cascade" are various S-nitrosothiols, which, like nitric oxide, activate soluble guanylate cyclase, inducing increased formation of cyclic guanosine monophosphate. NTG potentially may act to correct a localized deficiency of EDRF effect, at both the vasculature and platelet levels. In patients with unstable angina, hemodynamic effects and therapeutic efficacy of intravenously infused NTG may be attenuated within hours. Combined therapy with NTG and intravenously infused N-acetylcysteine (NAC) results in potentiation of hemodynamic responses to NTG, markedly augments the effects of NTG on platelet aggregation, and reduces the incidence of acute myocardial infarction in patients with severe unstable angina pectoris. The combination of NTG with intermittent NAC infusion may increase the risk of hypotensive episodes in such patients, whereas continuous coinfusion of the drugs is better tolerated. The combination of NTG with thiol-containing agents, such as NAC, may be of therapeutic value in unstable angina pectoris and in evolving acute myocardial infarction. This is currently under investigation.
不稳定型心绞痛和急性心肌梗死的发生是一个与局部冠状动脉血管收缩相关的血小板聚集和血栓形成过程。由于内皮衍生舒张因子（EDRF）生成减少导致的内皮血管舒张功能局部缺陷，可能易引发血小板聚集和冠状动脉血管收缩。硝酸甘油（NTG）常用于不稳定型心绞痛和急性心肌梗死的治疗，它通过一个依赖巯基的过程进行生物转化，生成一氧化氮，一氧化氮与EDRF相同或密切相关。硝酸盐生物转化“级联反应”的其他产物是各种S-亚硝基硫醇，它们与一氧化氮一样，激活可溶性鸟苷酸环化酶，导致环磷酸鸟苷生成增加。NTG可能在血管和血小板水平上纠正局部EDRF效应缺陷。在不稳定型心绞痛患者中，静脉输注NTG的血流动力学效应和治疗效果可能在数小时内减弱。NTG与静脉输注N-乙酰半胱氨酸（NAC）联合治疗可增强对NTG的血流动力学反应，显著增强NTG对血小板聚集的作用，并降低重度不稳定型心绞痛患者急性心肌梗死的发生率。NTG与间歇性NAC输注联合使用可能会增加此类患者发生低血压发作的风险，而持续联合输注药物的耐受性更好。NTG与含巯基药物（如NAC）联合使用可能对不稳定型心绞痛和进展中的急性心肌梗死具有治疗价值。目前正在对此进行研究。
