Abrams J
Department of Medicine (Cardiology), University of New Mexico School of Medicine, Albuquerque 87131, USA.
Am J Cardiol. 1996 May 30;77(13):31C-7C. doi: 10.1016/s0002-9149(96)00186-5.
Nitroglycerin and the long-acting nitrates have been used in cardiovascular medicine for >100 years. Nitrates are widely utilized for the various anginal syndromes and are also used in congestive heart failure and patients with left ventricular dysfunction. The potential mechanisms for relief of myocardial ischemia with nitrates are multiple. The nitrovasodilators are a related group of drugs that result in the formation of nitric oxide (NO) within vascular smooth muscle cells. NO stimulates the enzyme guanylate cyclase, which results in increases in cyclic guanosine monophosphate and vasodilation. In the presence of atherosclerosis, endothelial dysfunction is ubiquitous and associated with decreased NO availability, probably due to increased destruction of NO by free radical anions. Nitrovasodilators, including the nitrates, supply exogenous NO to the vascular wall and improve the vasodilator state. When nitrates are administered, endothelial-dependent stimuli cause relaxation rather than constriction in the setting of endothelial dysfunction. Nitrates also have antiplatelet effects, and recent evidence confirms that these drugs decrease platelet aggregation and thrombosis formation. This may play an important role in the therapy of acute unstable myocardial ischemia, including unstable angina and myocardial infarction. Nitrate hemodynamic effects have been long known. They are primarily modulated through a decrease in myocardial work that results from smaller cardiac chambers operating with lower systolic and diastolic pressures. These changes are caused by a redistribution of the circulating blood volume away from the heart to the venous capacitance system, with a fall in venous return to the heart. The afterload or arterial effects of nitrates are also useful in decreasing myocardial oxygen consumption. Considerable evidence confirms a variety of mechanisms whereby nitrates increase coronary blood flow, including epicardial coronary artery dilation, stenosis enlargement, enhanced collateral size and flow, improvement of endothelial dysfunction, and prevention or reversal of coronary artery vasoconstriction. These effects help increase nutrient coronary blood flow to zones of myocardial ischemia. Recent data with the nitroglycerin patch confirm that myocardial ischemia is decreased after nitrate administration. Nitroprusside, another nitrovasodilator, is a commonly used intravenous agent for lowering arterial pressure and left ventricular filling pressure. This drug is highly effective for the treatment of acute or severe hypertension and congestive heart failure. However, there are data suggesting that nitroprusside may be deleterious in the presence of acute myocardial ischemia, perhaps by shunting blood away from zones of jeopardized myocardial blood flow. Therefore, nitroprusside cannot be recommended to treat myocardial ischemia; intravenous nitroglycerin should be used in this context.
硝酸甘油和长效硝酸盐类药物在心血管医学领域已应用了100多年。硝酸盐类药物广泛用于各种心绞痛综合征，也用于充血性心力衰竭和左心室功能不全患者。硝酸盐类药物缓解心肌缺血的潜在机制是多方面的。硝基血管扩张剂是一类相关药物，可导致血管平滑肌细胞内一氧化氮（NO）的形成。NO刺激鸟苷酸环化酶，导致环磷酸鸟苷增加和血管扩张。在动脉粥样硬化存在的情况下，内皮功能障碍普遍存在，且与NO可用性降低有关，这可能是由于自由基阴离子对NO的破坏增加所致。硝基血管扩张剂，包括硝酸盐类药物，可向血管壁提供外源性NO并改善血管扩张状态。当给予硝酸盐类药物时，在内皮功能障碍的情况下，内皮依赖性刺激会引起舒张而非收缩。硝酸盐类药物还具有抗血小板作用，最近的证据证实这些药物可减少血小板聚集和血栓形成。这可能在急性不稳定型心肌缺血的治疗中发挥重要作用，包括不稳定型心绞痛和心肌梗死。硝酸盐类药物的血流动力学效应早已为人所知。它们主要通过减少心肌做功来调节，这是由于心脏腔室变小，收缩压和舒张压降低所致。这些变化是由循环血容量从心脏重新分布到静脉容量系统引起的，导致回心血量减少。硝酸盐类药物的后负荷或动脉效应在降低心肌氧耗方面也很有用。大量证据证实了硝酸盐类药物增加冠状动脉血流量的多种机制，包括心外膜冠状动脉扩张、狭窄扩大、侧支血管大小和血流量增加、内皮功能障碍改善以及冠状动脉血管收缩的预防或逆转。这些作用有助于增加心肌缺血区域的冠状动脉营养血流量。最近关于硝酸甘油贴片的数据证实，给予硝酸盐类药物后心肌缺血减少。硝普钠是另一种硝基血管扩张剂，是一种常用的静脉用药，用于降低动脉压和左心室充盈压。这种药物对治疗急性或重度高血压及充血性心力衰竭非常有效。然而，有数据表明，硝普钠在急性心肌缺血时可能有害，可能是通过使血液从濒危心肌血流区域分流。因此，不推荐使用硝普钠治疗心肌缺血；在此情况下应使用静脉硝酸甘油。
