Comparative Cardiotoxicity of Bupivacaine and Lidocaine in the Isolated Perfused Mammalian Heart
Comparative Cardiotoxicity of Bupivacaine and Lidocaine in the Isolated Perfused Mammalian Heart
复制标题
布比卡因和利多卡因在离体灌注哺乳动物心脏中的比较心脏毒性
作者：
Ralph D. Tanzs;Tammy Heskett;R. Loehning;C. Fairfax
本研究旨在比较布比卡因和利多卡因对离体灌注豚鼠 Langendorff 心脏制剂的直接作用。封固后 60 分钟，将盐酸布比卡因（0.3 或 3 μg/ml）或盐酸利多卡因（10 或 30 μg/ml）添加到灌注液中，并将效果（如果有）与 30、60 和 90 分钟后未处理的对照值进行比较。尽管两种药物的最高浓度总是会导致心率、df/dt、冠脉血流量和心肌耗氧量 (M&OV0312;O2) 显着降低，但在使用布比卡因后，这些降低幅度始终更大。此外，暴露于 3 μg/ml 布比卡因的心脏中，12 个制剂中有 6 个出现心律失常。这些心律失常最常见的是心脏传导阻滞和双联或三联律。其他研究表明，3 μg/ml 布比卡因产生的冠脉血流量和 M&O2 减少是其直接负性肌力和变时作用的结果。虽然布比卡因和利多卡因产生的心肌抑制可以通过替换新鲜灌注液而容易地逆转，但逐步增加细胞外钙浓度并不能增强3μg/ml布比卡因或10μg/ml利多卡因产生的负性肌力或变时作用。我们得出的结论是，在此模型中，3 ng/ml 未结合的布比卡因比 30 μg/ml 未结合的利多卡因更具心脏毒性。
This study was designed to compare the direct actions of bupivacaine and lidocaine on the isolated perfused guinea pig Langendorff heart preparation. Sixty min after mounting, either bupivacaine HCl (0.3 or 3 μg/ml) or lidocaine HCl (10 or 30 μg/ml) was added to the perfusate, and the effect (if any) was compared to untreated control values 30, 60, and 90 min later. Although the highest concentrations of both drugs invariably produced statistically significant reductions in heart rate, df/dt, coronary blood flow, and myocardial oxygen consumption (M&OV0312;O2), these reductions were consistently greater after bupivacaine. Moreover, arrhythmias occurred in 6 of 12 preparations in those hearts exposed to 3 μg/ml of bupivacaine. Most often these arrhythmias consisted of heart block and bi-or trigeminy. Additional studies indicated that the reduction in coronary blood flow and M&OV0312;O2 produced by 3 μg/ml of bupivacaine was a consequence of its direct negative inotropic and chronotropic action. Although the myocardial depression produced by bupivacaine and lidocaine could be reversed readily by substituting fresh perfusate, increasing the extracellular calcium concentration in stepwise increments did not augment the negative inotropic or chronotropic effect produced by 3 μg/ml of bupivacaine or 10 μg/ml of lidocaine. We conclude that 3 ng/ml of unbound bupivacaine is more cardiotoxic than 30 μg/ml of unbound lidocaine in this model.