Grover G J, Parham C S
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, NJ 08543-4000.
Eur J Pharmacol. 1987 Nov 3;143(1):109-17. doi: 10.1016/0014-2999(87)90740-0.
The purpose of this study was to determine if diltiazem can reduce the severity of pacing-induced ischemia independently of increases in overall and microregional ischemic blood flow. Sixteen anesthetized dogs were subjected to atrial pacing and had their left anterior descending coronary arteries (LAD) occluded until significant ST-elevation occurred. Cessation of pacing resulted in abolition of ST-segment elevation. ST-elevation as well as hemodynamics were measured during 5 min periods of pacing + LAD stenosis before, and 10, 40 and 70 min after treatment with intracoronary (i.c., just distal to the stenosis) diltiazem (1.8 micrograms/kg), i.v. diltiazem (180 micrograms/kg) or saline. Myocardial blood flow was measured using radioactive microspheres under baseline conditions, pacing, pacing + stenosis, and pacing + stenosis + drug (70 min post-drug). Both i.c. and i.v. diltiazem significantly and similarly reduced pacing-induced ST-elevation at 40 and 70 min post-drug with the highest measured reductions occurring for both at 70 min (50-60% reduction). Overall ischemic regional myocardial blood flow was unaffected by i.c. and i.v. diltiazem. Diltiazem given i.v. resulted in reduced flow in the lightly ischemic region and increased flows in the subepicardial half of the severely ischemic region. Diltiazem given i.c. resulted in a reduced subepicardial flow in the lightly ischemic region with no other changes occurring in the other regions. Thus, both i.c. and i.v. diltiazem can reduce the severity of pacing-induced ischemia and, in the doses given, in an equivalent fashion. Diltiazem also seems to be able to reduce severity of ischemia in a manner independent of increases in ischemic region flow and in fact can reduce flow in marginally ischemic tissue.
本研究的目的是确定地尔硫䓬能否在不依赖于整体和微血管区域缺血血流量增加的情况下,减轻起搏诱导的缺血严重程度。16只麻醉犬接受心房起搏,并将其左前降支冠状动脉(LAD)闭塞,直至出现明显的ST段抬高。起搏停止导致ST段抬高消失。在冠状动脉内(即狭窄远端)给予地尔硫䓬(1.8微克/千克)、静脉注射地尔硫䓬(180微克/千克)或生理盐水治疗前、治疗后10、40和70分钟,在起搏+LAD狭窄的5分钟期间测量ST段抬高以及血流动力学。在基线条件、起搏、起搏+狭窄以及起搏+狭窄+药物(给药后70分钟)情况下,使用放射性微球测量心肌血流量。冠状动脉内和静脉注射地尔硫䓬在给药后40和70分钟均能显著且相似地减轻起搏诱导的ST段抬高,两者在70分钟时测量到的最大降幅均为50 - 60%。冠状动脉内和静脉注射地尔硫䓬均未影响整体缺血区域的心肌血流量。静脉注射地尔硫䓬导致轻度缺血区域血流量减少,重度缺血区域心外膜下半部分血流量增加。冠状动脉内给予地尔硫䓬导致轻度缺血区域心外膜血流量减少,其他区域无其他变化。因此,冠状动脉内和静脉注射地尔硫䓬均能减轻起搏诱导的缺血严重程度,且在所给剂量下效果相当。地尔硫䓬似乎还能够以不依赖于缺血区域血流量增加的方式减轻缺血严重程度,事实上还能减少轻度缺血组织的血流量。