Endo T, Kiuchi K, Sato N, Hayakawa H, Maroko P R
First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Am Heart J. 1990 May;119(5):1002-7. doi: 10.1016/s0002-8703(05)80228-5.
To examine whether gallopamil (D600), a methoxy derivative of verapamil, has sustained beneficial effects on the ischemic myocardium, its effects on the size of myocardial infarction determined 6 hours (protocol 1) and 24 hours (protocol 2) after left anterior descending coronary artery occlusion were compared in anesthetized, open-chest dogs. To quantify the extent of the hypoperfused zone, Tc-99m- or In-111-albumin microspheres were injected into the left atrium 1 minute after occlusion. Fifteen minutes after occlusion, dogs were randomly assigned to a control group or a gallopamil-treated group that received immediately after assignment 0.08 mg/kg of gallopamil followed by a continuous infusion of 0.2 mg/kg/hr for 6 hours. Six or 24 hours after occlusion, the left ventricle was cut into 3 mm thick slices for triphenyltetrazolium chloride staining and autoradiography. There were no differences in the extent of the hypoperfused zone among the four groups. In both protocols 1 and 2 the ratio of the extent of myocardial necrosis to the extent of the hypoperfused zone was significantly smaller in the treated groups (56.7 +/- 6.7% [n = 8], p less than 0.01 and 72.3 +/- 5.3% [n = 6], p less than 0.05 for protocols 1 and 2, respectively) than in the control groups (100.7 +/- 6.0% [n = 7] and 95.2 +/- 4.3% [n = 5] for protocols I and II, respectively). Thus gallopamil administered early after coronary artery occlusion had beneficial effects on the ischemic myocardium, which were sustained for at least 24 hours after the onset of infarction.
为研究维拉帕米的甲氧基衍生物加洛帕米(D600)对缺血心肌是否具有持续有益作用,在麻醉开胸犬中比较了其对左冠状动脉前降支闭塞6小时(方案1)和24小时(方案2)后所测定的心肌梗死面积的影响。为量化灌注不足区域的范围,在闭塞后1分钟将锝-99m或铟-111标记的白蛋白微球注入左心房。闭塞15分钟后,将犬随机分为对照组或加洛帕米治疗组,治疗组在分组后立即静脉注射0.08mg/kg加洛帕米,随后以0.2mg/kg/小时的速度持续输注6小时。闭塞6或24小时后,将左心室切成3mm厚的切片进行氯化三苯基四氮唑染色和放射自显影。四组间灌注不足区域的范围无差异。在方案1和方案2中,治疗组心肌坏死范围与灌注不足区域范围的比值均显著小于对照组(方案1中分别为56.7±6.7%[n = 8],p<0.01;方案2中为72.3±5.3%[n = 6],p<0.05)(方案1和方案2对照组分别为100.7±6.0%[n = 7]和95.2±4.3%[n = 5])。因此,冠状动脉闭塞后早期给予加洛帕米对缺血心肌具有有益作用,且在梗死发生后至少持续24小时。