COMBINED EFFECTS OF DIFFERENT CLASS-I ANTIARRHYTHMIC AGENTS ON MAXIMUM RATE OF DEPOLARIZATION (VMAX) OF ACTION-POTENTIALS IN GUINEA-PIG PAPILLARY-MUSCLES

被引：3
作者：
HIRAOKA, M
NITTA, J
SUNAMI, A
SAWANOBORI, T
机构：
[1] Department of Cardiovascular Diseases, Medical Research Institute, Tokyo
[2] 2nd Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo
来源：
CARDIOVASCULAR DRUGS AND THERAPY | 1991年 / 5卷
关键词：
CLASS-I ANTIARRHYTHMIC AGENTS; COMBINATION THERAPY; VMAX; ACTION POTENTIALS; NA+ CURRENT; USE-DEPENDENT BLOCK;
D O I：
10.1007/BF00120827
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
The combination of two different kinds of class I antiarrhythmic agents (class Ia, Ib, or Ic) was examined with regard to their effects on the maximum rate of depolarization (V(max)) of action Potentials in guinea-pig papillary muscles. The combinations of disopyramide plus lidocaine, disopyramide plus mexiletine, mexiletine plus flecainide, and disopyramide plus flecainide were employed to study their effects on use-dependent block of V(max). All the combinations increased the percent of use-dependent block at most of the frequencies employed (0.1-3.3 Hz) as compared to the effects of the single use of either drug, but no decrease in use-dependent block was found with any of the combinations. The time courses of the development of use-dependent block by disopyramide, lidocaine, and mexiletine were best expressed by two exponential functions, whereas those by flecainide were expressed by a single exponential function. Disopyramide plus lidocaine and disopyramide plus mexiletine produced increases in the time constant of the fast component of the block (tau-f), the fast fraction of the block (A(f), and the ratio of the fast to the slow fraction (A(f)/A(s)). Mexiletine plus flecainide increased tau-f, A(f), and A(s); whereas disopyramide plus flecainide caused no changes in the kinetic parameters of use-dependent block. These results suggest that there may be diverse modes of interaction between the drug and the Na+ channel, and the combination of two different types of the drug may sometimes provide different effects on the fast and slow components of the use-dependent block of V(max).
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页码：791 / 800
页数：10
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