Chen F, Wetzel G T, Klitzner T S
Department of Pediatrics, University of California at Los Angeles, School of Medicine 90024.
Dev Pharmacol Ther. 1992;19(2-3):118-30. doi: 10.1159/000457473.
Recent studies suggest that amiodarone's acute clinical effects in infants and children are related predominantly to its class I antiarrhythmic activity. However, the effects of amiodarone on Na+ currents have not been investigated directly in immature cardiac cells. Accordingly, the tight seal whole cell voltage clamp technique was used to measure time- and voltage-dependent Na+ currents in acutely isolated neonatal ventricular myocytes from 2- to 5-day-old rabbits, before and after addition of amiodarone (0.1-10 microM). To evaluate the class I antiarrhythmic activity of amiodarone in this age group, the effects of amiodarone on Na+ currents were compared with those of procainamide. Similar to procainamide, amiodarone significantly decreased peak inward Na+ current in neonatal ventricular myocytes. Moreover, both amiodarone and procainamide shifted the steady-state inactivation curve to more negative membrane potentials and delayed recovery of the Na+ current from inactivation. Thus, the effects of amiodarone on the Na+ current in immature myocardium are qualitatively similar to those of procainamide, suggesting that amiodarone may act acutely as a class I antiarrhythmic agent in the newborn heart.
近期研究表明,胺碘酮对婴幼儿的急性临床作用主要与其Ⅰ类抗心律失常活性有关。然而,胺碘酮对钠电流的影响尚未在未成熟心肌细胞中直接进行研究。因此,采用紧密封接全细胞电压钳技术,在添加胺碘酮(0.1 - 10微摩尔)之前和之后,测量2至5日龄兔急性分离的新生心室肌细胞中时间和电压依赖性钠电流。为了评估胺碘酮在该年龄组的Ⅰ类抗心律失常活性,将胺碘酮对钠电流的影响与普鲁卡因胺的影响进行了比较。与普鲁卡因胺相似,胺碘酮显著降低了新生心室肌细胞内向钠电流峰值。此外,胺碘酮和普鲁卡因胺均使稳态失活曲线向更负的膜电位偏移,并延迟了钠电流从失活状态的恢复。因此,胺碘酮对未成熟心肌中钠电流的影响在性质上与普鲁卡因胺相似,这表明胺碘酮在新生儿心脏中可能作为Ⅰ类抗心律失常药物发挥急性作用。