Medlin R P, Ransom M M, Watts J A, Kline J A
Department of Emergency Medicine, Carolinas Medical Center, Charlotte 28232-2861, USA.
J Cardiovasc Pharmacol. 1996 Dec;28(6):792-8. doi: 10.1097/00005344-199612000-00009.
Haloperidol and lorazepam are commonly used to sedate ethanol (E)-intoxicated patients in emergency departments. This study was conducted to explore the role of ethanol in altering the potency of haloperidol and lorazepam with respect to cardiac conduction and contraction. For mechanical studies, isolated rat hearts were studied under isovolumetric conditions by using standard Langendorff technique. Hearts were perfused with Krebs-Heinseleit-Bicarbonate buffer containing haloperidol or lorazepam in concentrations ranging from 100 to 750 ng/ml (one heart per drug concentration). For both haloperidol and lorazepam individually, significant reductions in Left ventricular-generated pressure (LVGP) were observed at a concentration of 750 ng/ml (haloperidol = 2,250 nM and lorazepam = 2,000 nM). The addition of 20 and 65 mM ethanol shifted the concentration-response effect of haloperidol such that LVGP was significantly reduced at haloperidol = 500 and 300 ng/ml, respectively (p < 0.05 vs. basal control; paired t test). Ethanol produced no observable shift on the lorazepam concentration-response for LVGP. For electrophysiologic studies, hearts were perfused with haloperidol and lorazepam (300 ng/ml) +/- 65 mM ethanol. Compared with basal control, E + H significantly decreased heart rate (-74 +/- 12 beats/min) and increased His-ventricular conduction time (+7.6 +/- 1.5 ms vs. +1.7 +/- 0.6 ms for control hearts). Both haloperidol and EH significantly increased atrioventricular (AV) effective refractory period and the atrioventricular-His (AH) conduction interval. No significant changes in any electrophysiologic parameter were observed with ethanol or lorazepam perfused individually or with the combination of ethanol and lorazepam. Ethanol potentiates haloperidol-induced electromechanical depression of isolated rat hearts. Ethanol had no such effect on lorazepam.
在急诊科，氟哌啶醇和劳拉西泮常用于使乙醇（E）中毒患者镇静。本研究旨在探讨乙醇在改变氟哌啶醇和劳拉西泮对心脏传导和收缩的效力方面所起的作用。对于机械学研究，采用标准Langendorff技术在等容条件下研究离体大鼠心脏。用含有浓度范围为100至750 ng/ml氟哌啶醇或劳拉西泮的Krebs - Heinseleit - 碳酸氢盐缓冲液灌注心脏（每个药物浓度一颗心脏）。对于氟哌啶醇和劳拉西泮单独而言，在浓度为750 ng/ml（氟哌啶醇 = 2250 nM，劳拉西泮 = 2000 nM）时观察到左心室产生压力（LVGP）显著降低。添加20 mM和65 mM乙醇使氟哌啶醇的浓度 - 反应效应发生偏移，使得在氟哌啶醇分别为500 ng/ml和300 ng/ml时LVGP显著降低（与基础对照相比，p < 0.05；配对t检验）。乙醇对劳拉西泮的LVGP浓度 - 反应未产生可观察到的偏移。对于电生理学研究，用氟哌啶醇和劳拉西泮（300 ng/ml）±65 mM乙醇灌注心脏。与基础对照相比，E + H显著降低心率（-74 ± 12次/分钟）并延长希氏束 - 心室传导时间（对照心脏为+1.7 ± 0.6 ms，E + H为+7.6 ± 1.5 ms）。氟哌啶醇和EH均显著增加房室（AV）有效不应期和房室 - 希氏束（AH）传导间期。单独灌注乙醇或劳拉西泮或乙醇与劳拉西泮联合灌注时，未观察到任何电生理参数有显著变化。乙醇增强了氟哌啶醇诱导的离体大鼠心脏的机电抑制作用。乙醇对劳拉西泮无此作用。
