Iida M, Kodama I, Toyama J
Department of Circulation, Nagoya University, Japan.
Cardiovasc Res. 1996 Apr;31(4):640-50.
In a computer simulation study to mimic cardiac action potential, the total open time of the sodium channel at each excitation has been shown by other authors to be longer during propagation parallel (longitudinal, L) to fiber orientation than perpendicular (transverse, T) to that. If this is the case in actual cardiac tissue, the Class I antiarrhythmic drug action on conduction would be affected by their mode of sodium channel block. The present study was designed to test this hypothesis.
Effects of flecainide (F), quinidine (Q), aprindine (A) and SD3212 (S) on conduction velocity (theta), amplitude of extracellular potentials (phi e), and maximum upstroke velocity (Vmax) of action potentials were examined in isolated rabbit ventricular muscles with microscopic anisotropy.
F (0.1-1 microM) or Q (2-10 microM), which blocks the sodium channel mainly during the activated state, caused a concentration- and frequency-dependent decrease in theta and phi e. The reduction was more prominent during L than T propagation, giving rise to a decrease in their anisotropic ratio (theta L/theta T). A (1-5 microM) or S (3-10 microM), which blocks the channel during the inactivated state, also decreased theta and phi e. However, the reduction was similar during L and T propagation, and the anisotropic ratio of theta and phi e remained unaffected. The decrease of maximum upstroke velocity (Vmax) of action potential by F or Q was greater during L than T propagation; VmaxL/VmaxT was decreased significantly. In contrast, the Vmax reduction by A(3 microM) or S (10 microM) was similar during L and T propagation.
Different state-dependence of sodium channel block may underlie different negative dromotropic effects of Class I drugs in anisotropic cardiac muscle.
在一项模拟心脏动作电位的计算机模拟研究中，其他作者已表明，在与纤维方向平行（纵向，L）传播时，每次兴奋时钠通道的总开放时间比垂直（横向，T）于纤维方向传播时更长。如果在实际心脏组织中也是如此，那么I类抗心律失常药物对传导的作用将受到其钠通道阻滞方式的影响。本研究旨在验证这一假设。
在具有微观各向异性的离体兔心室肌中，研究了氟卡尼（F）、奎尼丁（Q）、阿普林定（A）和SD3212（S）对传导速度（θ）、细胞外电位幅度（φe）和动作电位最大上升速度（Vmax）的影响。
主要在激活状态下阻滞钠通道的F（0.1 - 1微摩尔）或Q（2 - 10微摩尔），导致θ和φe呈浓度和频率依赖性降低。在L向传播时的降低比T向传播时更显著，导致其各向异性比率（θL/θT）降低。主要在失活状态下阻滞通道的A（1 - 5微摩尔）或S（3 - 10微摩尔），也降低了θ和φe。然而，在L向和T向传播时的降低相似，θ和φe的各向异性比率保持不变。F或Q使动作电位最大上升速度（Vmax）的降低在L向传播时比T向传播时更大；VmaxL/VmaxT显著降低。相比之下，A（3微摩尔）或S（10微摩尔）使Vmax的降低在L向和T向传播时相似。
钠通道阻滞的不同状态依赖性可能是I类药物在各向异性心肌中产生不同负性变传导作用的基础。
