Rosen M A, Thigpen J W, Shnider S M, Foutz S E, Levinson G, Koike M
Anesth Analg. 1985 Nov;64(11):1089-96.
Awake, unanesthetized, and paralyzed sheep made hypoxic and acidotic were given equivalent low and high intravenous doses of lidocaine and bupivacaine over 10 sec. Within 30 sec of injections, all animals had electroencephalographic evidence of convulsions. After administration of low-dose lidocaine, arrhythmias associated with significant hemodynamic changes did not occur; after administration of high-dose lidocaine, half of the animals became hypotensive but had no arrhythmias other than sinus tachycardia. However, after administration of low-dose bupivacaine, all sheep had evidence of serious electrocardiographic changes or arrhythmias, and one animal died. After administration of high-dose bupivacaine, serious electrocardiographic changes occurred in all animals, and despite resuscitative efforts, all died. The most common abnormality after bupivacaine administration was a wide-QRS-complex bradycardia, occurring in most animals regardless of dose. Two-thirds of the animals given high-dose bupivacaine had electromechanical dissociation and subsequent refractory asystole. Although the mechanism of action is not known, bupivacaine appears to be more cardiotoxic than lidocaine. This toxicity is enhanced in animals by the presence of hypercarbia, acidosis, and hypoxia.
对清醒、未麻醉且已瘫痪的绵羊造成低氧血症和酸中毒，在10秒内静脉注射等量的低剂量和高剂量利多卡因及布比卡因。注射后30秒内，所有动物均有脑电图显示惊厥。给予低剂量利多卡因后，未出现伴有显著血流动力学变化的心律失常；给予高剂量利多卡因后，一半动物出现低血压，但除窦性心动过速外无其他心律失常。然而，给予低剂量布比卡因后，所有绵羊均有严重心电图改变或心律失常的迹象，且有一只动物死亡。给予高剂量布比卡因后，所有动物均出现严重心电图改变，尽管进行了复苏努力，但所有动物均死亡。布比卡因给药后最常见的异常是宽QRS波群心动过缓，大多数动物无论剂量如何都会出现。三分之二给予高剂量布比卡因的动物出现电机械分离及随后的顽固性心搏停止。尽管作用机制尚不清楚，但布比卡因似乎比利多卡因更具心脏毒性。高碳酸血症、酸中毒和低氧血症会增强动物的这种毒性。
