Jugdutt B I
Department of Medicine, University of Alberta, Edmonton, Canada.
Cardiovasc Drugs Ther. 1994 Aug;8(4):635-46. doi: 10.1007/BF00877417.
Until two decades ago nitroglycerin was contraindicated in acute myocardial infarction (MI). Studies in the canine model demonstrated that low-dose intravenous (i.v.) infusion, carefully titrated to decrease mean blood pressure by 10% but not below 80 mmHg, during early stages of acute MI produced marked reduction of left ventricular (LV) preload, improvement in regional perfusion, and limitation of infarct size and remodeling. However, more i.v. nitroglycerin to decrease blood pressure further resulted in a paradoxical J-curve effect, with hypoperfusion and increased infarct size. Clinical studies have confirmed that low-dose i.v. nitroglycerin infusion for the first 48 hours after acute MI is safe, not only for improving performance in LV failure, but also for limiting ischemic injury, infarct size, remodeling, and infarct-related complications, including deaths in-hospital and up to 1 year. Recent studies suggest that more prolonged therapy with nitrates spanning the healing phase of acute anterior Q-wave MI can further limit LV remodeling and preserve function. Preliminary results of the recently completed ISIS-4 megatrial suggest, however, that long-term nitrate in patients with suspected MI in the 1990s does not improve survival significantly.
直到二十年前,硝酸甘油在急性心肌梗死(MI)中还是禁忌药物。对犬类模型的研究表明,在急性心肌梗死早期,小心滴定低剂量静脉注射(i.v.)硝酸甘油以降低平均血压10%但不低于80 mmHg,可显著降低左心室(LV)前负荷,改善局部灌注,并限制梗死面积和重塑。然而,更多的静脉注射硝酸甘油进一步降低血压会导致矛盾的J曲线效应,即灌注不足和梗死面积增加。临床研究证实,急性心肌梗死后最初48小时内低剂量静脉注射硝酸甘油不仅对改善左心室衰竭的表现安全,而且对限制缺血性损伤、梗死面积、重塑以及梗死相关并发症(包括住院死亡和长达1年的死亡)也安全。最近的研究表明,在急性前壁Q波心肌梗死愈合阶段进行更长时间的硝酸盐治疗可进一步限制左心室重塑并保留功能。然而,最近完成的ISIS-4大型试验的初步结果表明,20世纪90年代疑似心肌梗死患者长期使用硝酸盐并不能显著提高生存率。