Ye V Z, Wyse K R, Campbell T J
Department of Cardiology, St. Vincent's Hospital, Sydney, Australia.
J Cardiovasc Pharmacol. 1993 Jan;21(1):47-55. doi: 10.1097/00005344-199301000-00008.
We have previously shown reduced selectivity for depolarized and acidotic myocardium for encainide and flecainide compared to lidocaine and amiodarone. The present study aims to compare propafenone and two of its metabolites (5-OH-propafenone and N-despropyl-propafenone) to lidocaine in the same model. Standard microelectrode methods were used to record intracellular action potentials from strips of guinea pig right ventricular myocardium superfused with either standard physiological saline (pH 7.3; pO2 > 600 mm Hg; [K+] = 5.6 mM), or the same solution modified to produce either hyperkalemia (K+ = 11.2 mM), acidosis (pH = 6.3), or hypoxia (pO2 = 60 mm Hg). The effects on action potential parameters of three "therapeutic" concentrations of lidocaine, propafenone, and two of its metabolites were studied under all four conditions at four different drive rates from 200 to 25 beats/min. Hyperkalemia, in the absence of drugs, produced reductions in the resting potential (-86.7 +/- 2.5 to -71.8 +/- 3.7 mV) and the maximum rate of depolarization (Vmax, 300.0 +/- 46.5 to 205.6 +/- 37.6 V/s). All four drugs produced increased depression of Vmax in hyperkalemia and acidosis compared to control conditions, but it was a consistent finding that at concentrations that were approximately equipotent in control conditions, lidocaine produced greater increments in depression of Vmax in hyperkalemic and acidotic superfusate than did propafenone or either of its metabolites. Qualitatively similar results were obtained for both metabolites compared to lidocaine. Hypoxia produced no significant modulation of drug effects.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前已经表明，与利多卡因和胺碘酮相比，恩卡尼和氟卡尼对去极化和酸中毒心肌的选择性降低。本研究旨在在同一模型中比较普罗帕酮及其两种代谢产物（5-羟基普罗帕酮和N-去丙基普罗帕酮）与利多卡因。采用标准微电极方法记录豚鼠右心室心肌条的细胞内动作电位，心肌条用标准生理盐水（pH 7.3；pO2>600 mmHg；[K+]=5.6 mM）或经改良以产生高钾血症（K+=11.2 mM）、酸中毒（pH=6.3）或低氧（pO2=60 mmHg）的相同溶液进行灌流。在四种不同的驱动频率（200至25次/分钟）下，研究了三种“治疗”浓度的利多卡因、普罗帕酮及其两种代谢产物在所有四种条件下对动作电位参数的影响。在无药物情况下，高钾血症导致静息电位降低（从-86.7±2.5 mV降至-71.8±3.7 mV）以及最大去极化速率降低（Vmax，从300.0±46.5 V/s降至205.6±37.6 V/s）。与对照条件相比，所有四种药物在高钾血症和酸中毒时均使Vmax的抑制作用增强，但一个一致的发现是，在对照条件下大致等效的浓度下，利多卡因在高钾血症和酸中毒灌流液中使Vmax抑制作用的增加幅度大于普罗帕酮或其任何一种代谢产物。与利多卡因相比，两种代谢产物获得了定性相似的结果。低氧对药物效应无显著调节作用。（摘要截短于250字）
