Freysz M, Timour Q, Bertrix L, Loufoua J, Aupetit J F, Faucon G
Department of Medical Pharmacology, Claude Bernard University, Lyon, France.
Anesth Analg. 1995 Apr;80(4):657-63. doi: 10.1097/00000539-199504000-00002.
Myocardial ischemia sensitizes the cardiotoxic effects of bupivacaine, especially the propensity to ventricular fibrillation. To investigate this sensitization and to elucidate its mechanism, the influence of bupivacaine alone, or associated with ischemia, was studied on electrical fibrillation threshold in anesthetized, open chest pigs. Determination of fibrillation threshold was performed with impulses of 100 ms duration at the rate of 180 bpm, in the absence of ischemia and at the end of increasing periods of ischemia (30, 60, 120, 180 s) obtained by complete occlusion of the left anterior descending coronary artery close to its origin. The effect of bupivacaine (1.00 mg/kg initial dose plus 0.04 mg.kg-1.min-1 over 25 min) was compared to the control in the same animals. This effect corresponded to 1.4-1.8 micrograms/mL plasma concentrations likely to be observed in humans after regional anesthesia. Bupivacaine significantly increased the fibrillation threshold before coronary occlusion from approximately 7.0 to 9.5 mA. In contrast, during ischemia the fibrillation threshold was shifted to the left and down, with a hastening of spontaneous fibrillation. Recording of monophasic action potentials in the ischemic area revealed that conduction time was prolonged by more than 100% under the combined influence of ischemia and bupivacaine, whereas the major enhancement of excitability due to ischemia was not attenuated by bupivacine. Therefore, bupivacaine should be used with caution in the condition of ischemia, especially if heart rate is rapid. In the present experiments, tachycardia is another factor in the enhancement of bupivacaine effects on conduction.
心肌缺血会使布比卡因的心脏毒性作用增强，尤其是增加心室颤动的倾向。为了研究这种敏感性并阐明其机制，我们在麻醉开胸猪身上研究了单独使用布比卡因或与缺血联合使用时对电颤阈的影响。在无缺血状态下以及通过完全闭塞左冠状动脉前降支近端使其缺血时间逐渐增加（30、60、120、180秒）后，以180次/分钟的频率施加100毫秒持续时间的脉冲来测定电颤阈。将布比卡因（初始剂量1.00毫克/千克，随后25分钟内以0.04毫克·千克⁻¹·分钟⁻¹给药）的作用与同一动物的对照组进行比较。这种效应相当于区域麻醉后人体血浆中可能观察到的1.4 - 1.8微克/毫升的浓度。在冠状动脉闭塞前，布比卡因显著提高了电颤阈，从约7.0毫安提高到9.5毫安。相比之下，在缺血期间，电颤阈向左下方移动，同时自发颤动加速。对缺血区域单相动作电位的记录显示，在缺血和布比卡因的联合影响下，传导时间延长超过100%，而缺血引起的兴奋性主要增强并未被布比卡因减弱。因此，在缺血情况下使用布比卡因应谨慎，尤其是心率较快时。在本实验中，心动过速是增强布比卡因对传导作用的另一个因素。
