Gewirtz H, Gross S L, Williams D O, Most A S
Circulation. 1984 May;69(5):1048-57. doi: 10.1161/01.cir.69.5.1048.
This study tested the hypothesis that intrinsic negative inotropic effects of a drug used to induce coronary vasodilation distal to a severe coronary arterial stenosis may influence the extent of redistribution of transmural flow and its metabolic consequences. To test this hypothesis, studies were conducted in eight closed-chest, sedated swine with severe (82% reduction in luminal diameter) coronary arterial stenoses. Measurement of hemodynamic parameters, regional myocardial blood flow (microsphere technique), lactate metabolism, and oxygen consumption were made (1) under control conditions, (2) after 10 min of intracoronary infusion of a vasodilator distal to the stenosis, and (3) under repeat control conditions. Each animal received both intracoronary adenosine (400 micrograms/min) and nifedipine (50 micrograms/min). The order of drug infusion was chosen at random and a control period separated administration of each. In response to nifedipine there was no significant change in the group mean (+/- SD) value of endocardial flow (1.21 +/- 0.34 to 1.29 +/- 0.61 ml/min X g-1) distal to the stenosis. In contrast, epicardial flow increased in comparison with control in response to nifedipine (1.30 +/- 0.58 to 1.79 +/- 0.74 ml/min X g-1; p less than .05). Regional myocardial oxygen consumption (MVO2) declined in comparison with control in response to nifedipine (14.0 +/- 4.2 to 11.1 +/- 5.0 ml/min X 100 g-1; p less than .05). Regional lactate extraction did not change in comparison with control during infusion of nifedipine (18.2 +/- 22.4 vs 11.7 +/- 16.8). In response to adenosine, endocardial blood flow distal to the stenosis declined in comparison with control (1.25 +/- 0.53 to 1.07 +/- 0.38 ml/min X g-1; p less than .05), while epicardial flow increased (1.31 +/- 0.55 to 2.26 +/- 0.59 ml/min X g-1; p less than .01). Regional MVO2 also tended to decline in comparison with control in response to adenosine (13.4 +/- 4.9 to 11.7 +/- 2.9 ml/min X 100 g-1) and was significantly (p less than .05) reduced in comparison with postintervention control (14.6 +/- 4.2 ml/min X 100 g-1). In contrast to nifedipine, adenosine caused a significant decline in regional lactate extraction in comparison with control (12.7 +/- 23.2% to -40.6 +/- 55.0%; p less than .01). Thus, administration of nifedipine, a negative inotropic agent, resulted in (1) a decline in regional MVO2, (2) increased epicardial blood flow with variable effects on endocardial flow distal to the stenosis, and (3) no evidence of de novo or worsening ischemia, even in animals in which endocardial flow decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
用于诱导严重冠状动脉狭窄远端冠状动脉血管舒张的药物的内在负性肌力作用，可能会影响透壁血流再分布的程度及其代谢后果。为验证该假设，对8只闭胸、镇静的患有严重（管腔直径减少82%）冠状动脉狭窄的猪进行了研究。在以下情况下进行了血流动力学参数、局部心肌血流量（微球技术）、乳酸代谢和氧消耗的测量：（1）在对照条件下；（2）在狭窄远端冠状动脉内输注血管扩张剂10分钟后；（3）在重复对照条件下。每只动物均接受冠状动脉内腺苷（400微克/分钟）和硝苯地平（50微克/分钟）。药物输注顺序随机选择，且每次给药之间有一个对照期。硝苯地平给药后，狭窄远端的心内膜血流组均值（±标准差）值无显著变化（从1.21±0.34至1.29±0.61毫升/分钟×克-1）。相比之下，硝苯地平给药后，心外膜血流与对照相比增加（从1.30±0.58至1.79±0.74毫升/分钟×克-1；p<0.05）。硝苯地平给药后，局部心肌氧消耗（MVO2）与对照相比下降（从14.0±4.2至11.1±5.0毫升/分钟×100克-1；p<0.05）。硝苯地平输注期间，局部乳酸摄取与对照相比无变化（18.2±22.4对11.7±16.8）。腺苷给药后，狭窄远端的心内膜血流与对照相比下降（从1.25±0.53至1.07±0.38毫升/分钟×克-1；p<0.05），而心外膜血流增加（从1.31±0.55至2.26±0.59毫升/分钟×克-1；p<0.01）。腺苷给药后，局部MVO2与对照相比也有下降趋势（从13.4±4.9至11.7±2.9毫升/分钟×100克-1），且与干预后对照（14.6±4.2毫升/分钟×100克-1）相比显著降低（p<0.05）。与硝苯地平相反，腺苷给药后局部乳酸摄取与对照相比显著下降（从12.7±23.2%至-40.6±55.0%；p<0.01）。因此，负性肌力药物硝苯地平的给药导致：（1）局部MVO2下降；（2）心外膜血流增加，对狭窄远端的心内膜血流有不同影响；（3）即使在心内膜血流减少的动物中，也没有新的或恶化的缺血证据。（摘要截断于400字）
