Stowe D F, Habazettl H, Graf B M, Kampine J P, Bosnjak Z J
Departments of Anesthesiology and Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Anesthesiology. 1995 Nov;83(5):1065-77. doi: 10.1097/00000542-199511000-00020.
Halothane exerts a potent negative inotropic effect on the heart and mimics many of the cardiac effects of lowered extracellular CaCl2. Reduced slow inward Ca2+ current and sarcoplasmic reticular effects on intracellular Ca2+ are likely involved. The authors reported previously that halothane protects against hypoxic and ischemia reperfusion injury in isolated hearts. The aim of this isolated heart study was to compare protective effects of halothane and low CaCl2 (0.5 mM) administered during 1 day of hypothermic perfusion on return of normothermic perfusion.
Guinea pig hearts (n = 66) were isolated and perfused at 37 degrees C with a Krebs' solution, gassed with 96% O2, 4% CO2, and containing 2.5 mM Ca2+, and 4.5 mM K+. Heart rate, isovolumetric left ventricular pressure, coronary flow, %O2 extraction, O2 consumption rate, and relative cardiac efficiency (EFF = heart rate.left ventricular pressure/O2 consumption rate) were measured in five groups of hearts: time controls (no hypothermia); 1.5, and 3% halothane delivered by vaporizer; cold controls (hypothermia only); and 0.5 mM CaCl2. Halothane was administered, or CaCl2 was decreased 0.5 h before hypothermia at 3.8 +/- 0.1 degrees C, during hypothermia for 22 h, and for 0.5 h after rewarming to 37.0 +/- 0.1 degrees C. Hearts were perfused at 25% of initial coronary flow during hypothermia.
All groups had similar ventricular function and vasodilator responses before hypothermia. During normothermic reperfusion after hypothermia, both concentrations of halothane protected better than low CaCl2. Values, expressed as a percent of initial values in the five groups (time control, 3% halothane, 1.5% halothane, cold control, and 0.5 mM CaCl2, were respectively: 90 +/- 6, 54 +/- 6*, 48 +/- 5*, 27 +/- 8, 27 +/- 4% for left ventricular pressure; 84 +/- 5, 61 +/- 4*, 62 +/- 6*, 40 +/- 5, 34 +/- 5% for EFF; and 102 +/- 3, 63 +/- 3*, 66 +/- 3*, 55 +/- 2, 42 +/- 2% for coronary flow (*P < 0.05 halothane vs. 0.5 mM CaCl2). The coronary flow response to endothelium-dependent (acetylcholine) and endothelium-independent (nitroprusside) vasodilators was also greater after halothane than after 0.5 mM CaCl2.
Halothane administered during hypothermia restores left ventricular pressure, cardiac efficiency, basal coronary flow, and flow responses better than low CaCl2. Although halothane and low CaCl2 both reduce intracellular Ca2+, contractile force, and metabolic demand, the better protective effect of halothane is not likely simply due to a reduction in contractile function and metabolic rate before or initially after hypothermia because these were reduced much more by low CaCl2 than by halothane.
氟烷对心脏有强大的负性肌力作用，可模拟细胞外氯化钙浓度降低时的许多心脏效应。可能涉及慢内向钙电流减少以及肌浆网对细胞内钙的作用。作者之前报道过氟烷可保护离体心脏免受缺氧和缺血再灌注损伤。本离体心脏研究的目的是比较在低温灌注1天期间给予氟烷和低氯化钙（0.5 mM）对恢复正常体温灌注的保护作用。
分离豚鼠心脏（n = 66），在37℃用含2.5 mM氯化钙和4.5 mM钾的克雷布斯溶液灌注，通以96%氧气、4%二氧化碳。在五组心脏中测量心率、等容左心室压力、冠状动脉流量、氧提取率、氧消耗率和相对心脏效率（EFF = 心率×左心室压力/氧消耗率）：时间对照组（无低温）；通过蒸发器给予1.5%和3%氟烷；冷对照组（仅低温）；以及0.5 mM氯化钙。在3.8±0.1℃低温前0.5小时给予氟烷，或降低氯化钙浓度，在低温期间持续22小时，并在复温至37.0±0.1℃后0.5小时。低温期间以初始冠状动脉流量的25%进行灌注。
所有组在低温前具有相似的心室功能和血管舒张反应。在低温后的常温再灌注期间，两种浓度的氟烷的保护作用均优于低氯化钙。以五组初始值的百分比表示的值（时间对照组、3%氟烷组、1.5%氟烷组、冷对照组和0.5 mM氯化钙组）分别为：左心室压力：90±6、54±6*、48±5*、27±8、27±4%；EFF：84±5、61±4*、62±6*、40±5、34±5%；冠状动脉流量：102±3、63±3*、66±3*、55±2、42±2%（*氟烷与0.5 mM氯化钙相比，P < 0.05）。氟烷后对内皮依赖性（乙酰胆碱）和内皮非依赖性（硝普钠）血管舒张剂的冠状动脉流量反应也大于0.5 mM氯化钙后。
低温期间给予氟烷比低氯化钙能更好地恢复左心室压力、心脏效率、基础冠状动脉流量和流量反应。虽然氟烷和低氯化钙均降低细胞内钙、收缩力和代谢需求，但氟烷更好的保护作用不太可能仅仅归因于低温前或低温后初期收缩功能和代谢率的降低，因为低氯化钙比氟烷对这些指标的降低幅度更大。
