Crystal G J, Kim S J, Salem M R, Khoury E, Gurevicius J
Department of Anesthesiology, Illinois Masonic Medical Center, Chicago 60657.
Anesthesiology. 1994 Jul;81(1):209-20. doi: 10.1097/00000542-199407000-00027.
Isoflurane causes vasodilation in the coronary circulation. The current study employed a canine model permitting selective intracoronary administrations of isoflurane (1) to test the hypothesis that coronary vasodilation by isoflurane is mediated by nitric oxide and (2) to evaluate the persistence of coronary vasodilation during an extended exposure to isoflurane.
Open-chest dogs anesthetized with fentanyl and midazolam were studied. The left anterior descending coronary artery (LAD) was perfused via extracorporeal system with normal arterial blood or with arterial blood equilibrated with 1.4% (1 MAC) isoflurane. In the LAD bed, coronary blood flow (CBF) was measured with an electromagnetic flowmeter and used to calculate myocardial oxygen consumption (MVO2). In series 1, performed at constant coronary perfusion pressure (CPP), the LAD was exposed to 3 h of isoflurane in two groups of eight dogs: control group, normal coronary endothelium; and experimental group, intracoronary infusion of the nitric oxide synthase inhibitor L-NAME (0.15 mg/min for 30 min). Series 2 was performed with CBF constant; thus, CPP varied directly with coronary vascular resistance. In this series, initial steady-state changes in CPP by isoflurane were evaluated in the same four dogs before and after L-NAME.
In the control group of series 1, isoflurane caused a maximal, initial increase in CBF of 444%; however, CBF decreased progressively reaching a value not significantly different from baseline after 3 h of isoflurane. Isoflurane caused a significant (approximately 35%) decrease in MVO2, which persisted during the 3-h administration. Findings after L-NAME (experimental group) were not significantly different from those in control group. In series 2, isoflurane caused significant decreases in CPP that were not affected by L-NAME.
The lack of effect of L-NAME on isoflurane-induced coronary vasodilation suggests that nitric oxide does not mediate this response. The increase in CBF during prolonged isoflurane waned over time, perhaps because of tachyphylaxis or emergence of a competitive vasoconstrictor mechanism, e.g., metabolic factors secondary to reduced oxygen demands.
异氟烷可导致冠状动脉循环血管舒张。本研究采用一种犬类模型，允许选择性冠状动脉内给予异氟烷，（1）以检验异氟烷引起冠状动脉血管舒张由一氧化氮介导的假说，（2）并评估长时间暴露于异氟烷期间冠状动脉血管舒张的持续性。
对用芬太尼和咪达唑仑麻醉的开胸犬进行研究。通过体外系统用正常动脉血或用与1.4%（1MAC）异氟烷平衡的动脉血灌注左前降支冠状动脉（LAD）。在LAD床，用电磁流量计测量冠状动脉血流量（CBF），并用于计算心肌耗氧量（MVO2）。在系列1中，在恒定冠状动脉灌注压（CPP）下进行，将LAD暴露于异氟烷3小时，分为两组，每组8只犬：对照组，冠状动脉内皮正常；实验组，冠状动脉内输注一氧化氮合酶抑制剂L-NAME（0.15mg/min，持续30分钟）。系列2在CBF恒定的情况下进行；因此，CPP随冠状动脉血管阻力直接变化。在该系列中，在给予L-NAME之前和之后，在同4只犬中评估异氟烷引起的CPP的初始稳态变化。
在系列1的对照组中，异氟烷使CBF最初最大增加444%；然而，异氟烷作用3小时后，CBF逐渐下降，降至与基线无显著差异的值。异氟烷使MVO2显著降低（约35%），在3小时给药期间持续存在。给予L-NAME后的结果（实验组）与对照组无显著差异。在系列2中，异氟烷使CPP显著降低，且不受L-NAME影响。
L-NAME对异氟烷诱导的冠状动脉血管舒张无作用，提示一氧化氮不介导此反应。长时间异氟烷作用期间CBF的增加随时间减弱，可能是因为快速耐受或出现竞争性血管收缩机制，例如继发于氧需求降低的代谢因素。
