Krishnan S C, Antzelevitch C
Masonic Medical Research Laboratory, Utica, N.Y. 13504.
Circ Res. 1991 Aug;69(2):277-91. doi: 10.1161/01.res.69.2.277.
Using microelectrode techniques we compared the effects of tetrodotoxin (TTX, 2-3 microM), DL-propranolol (1-3 micrograms/ml), and flecainide acetate (10-15 microM) on isolated canine ventricular epicardial (epicardium) and endocardial (endocardium) tissues. Propranolol, TTX, and flecainide decreased Vmax and phase 0 amplitude in a use-dependent manner in both tissues. The effects of propranolol were slow to develop and wash out. TTX and propranolol always abbreviated action potential duration in endocardium. Action potential duration was abbreviated by 23.8 +/- 5.6 msec after propranolol (1 microgram/ml, basic cycle length [BCL] = 1,000 msec) and 10.8 +/- 12.9 msec after TTX (2 microM, BCL = 1,000 msec). In epicardium, the reduction of phase 0 and 1 amplitudes led to a slowing of the second action potential upstroke and an increase in the amplitude of phase 2. This accentuation of the notch resulted in a paradoxical prolongation of the epicardial action potential. Action potential duration was prolonged 34.4 +/- 11.3 msec after 4 hours of exposure to propranolol (1 microgram/ml, BCL = 1,000 msec), 11.1 +/- 6.3 msec after 15 minutes of exposure to TTX (2 microM, BCL = 1,000 msec), and 19.9 +/- 8.2 msec after 25-45 minutes of exposure to flecainide (15 microM, BCL = 500 msec). With stronger sodium block, phase 1 terminated at more negative potentials, the second upstroke often failed to appear, and an all-or-none repolarization ensued causing a marked abbreviation of the epicardial action potential. In some epicardial preparations, we observed marked abbreviation at some sites but prolongation at other sites after sodium blockade with flecainide. The dispersion of repolarization was often attended by reentrant activity. The differential response of epicardium and endocardium to sodium blockade was not observed when the preparations were pretreated with 4-aminopyridine or ryanodine, agents known to diminish the transient outward current and epicardial notch. Acceleration-induced prolongation of refractoriness was observed after sodium blockade in epicardium but not in endocardium. Postrepolarization refractoriness also occurred in epicardium but not in endocardium after TTX, propranolol, or flecainide exposure. The data indicate that propranolol, TTX, and flecainide, via their action to block sodium current, may exert opposite effects on action potential duration and refractoriness in cells spanning the ventricular wall. The presence of the transient outward current in epicardium but not in endocardium appears to contribute importantly to these differences.(ABSTRACT TRUNCATED AT 400 WORDS)
我们运用微电极技术，比较了河豚毒素（TTX，2 - 3微摩尔）、DL - 普萘洛尔（1 - 3微克/毫升）和醋酸氟卡尼（10 - 15微摩尔）对离体犬心室心外膜（epicardium）和心内膜（endocardium）组织的影响。普萘洛尔、TTX和氟卡尼在两种组织中均以使用依赖的方式降低Vmax和0期振幅。普萘洛尔的作用起效缓慢且消除也慢。TTX和普萘洛尔总是缩短心内膜的动作电位时程。在普萘洛尔（1微克/毫升，基础周期长度[BCL]=1000毫秒）作用后，动作电位时程缩短23.8±5.6毫秒；在TTX（2微摩尔，BCL = 1000毫秒）作用后，缩短10.8±12.9毫秒。在心外膜，0期和1期振幅的降低导致第二个动作电位上升支减慢以及2期振幅增加。这种切迹的加重导致心外膜动作电位出现反常延长。在暴露于普萘洛尔（1微克/毫升，BCL = 1000毫秒）4小时后，动作电位时程延长34.4±11.3毫秒；在暴露于TTX（2微摩尔，BCL = 1000毫秒）15分钟后，延长11.1±6.3毫秒；在暴露于氟卡尼（15微摩尔，BCL = 500毫秒）25 - 45分钟后，延长19.9±8.2毫秒。随着更强的钠通道阻滞，1期在更正电位时终止，第二个上升支常未出现，随后出现全或无的复极化，导致心外膜动作电位显著缩短。在一些心外膜标本中，用氟卡尼进行钠通道阻滞后，我们在一些部位观察到显著缩短，而在其他部位观察到延长。复极离散常伴有折返活动。当标本用4 - 氨基吡啶或ryanodine预处理时，未观察到心外膜和心内膜对钠通道阻滞的不同反应，已知这两种药物可减少瞬时外向电流和心外膜切迹。在心外膜钠通道阻滞后观察到加速诱导的不应期延长，而在心内膜未观察到。在暴露于TTX、普萘洛尔或氟卡尼后，心外膜也出现复极后不应期，而心内膜未出现。数据表明，普萘洛尔、TTX和氟卡尼通过其阻断钠电流的作用，可能对跨越心室壁的细胞的动作电位时程和不应期产生相反的影响。心外膜中存在瞬时外向电流而心内膜中不存在，这似乎对这些差异起重要作用。（摘要截断于400字）
