Varró A, Lathrop D A, Surawicz B
Krannert Institute of Cardiology, Department of Medicine, Indiana University College of Medicine, Indianapolis.
J Cardiovasc Pharmacol. 1990 Nov;16(5):757-63. doi: 10.1097/00005344-199011000-00010.
We compared the effects of a low (0.09 microgram/ml) concentration of propranolol expected to produce only beta-adrenoceptor blockade and a high concentration (0.9 microgram/ml) expected to produce additional direct local anesthetic-like electrophysiological effects on basic and premature action potentials. Both isolated dog cardiac Purkinje and ventricular muscle fibers were examined using conventional microelectrode techniques. The low concentration of propranolol produced no significant electrophysiological change in either fiber type. The high concentration of propranolol shortened the action potential duration and refractoriness while decreasing the maximal upstroke velocity (Vmax) in both Purkinje and ventricular muscle fibers at a constant basic cycle length. In Purkinje fibers, the high concentration also slowed the kinetics of restitution of the action potential duration (tau c from 124.6 +/- 6.5 to 201.4 +/- 16.0 ms, p less than 0.01, n = 7), slowed the recovery kinetics of Vmax, and shifted the early portion of the normalized restitution curve toward longer action potential duration values in both fiber types. The range of premature action potential durations, defined as the difference between action potential durations during the first 100 ms of restitution, was decreased by the high concentration of propranolol in both Purkinje and ventricular muscle fibers by 39.5% and 33.9%, respectively. These findings indicate that (a) low concentrations of propranolol produced no direct electrophysiological effect, and (b) high concentrations of propranolol produced several potential antiarrhythmic effects in addition to the previously reported effects on Vmax and the action potential duration.
我们比较了低浓度（0.09微克/毫升）普萘洛尔预期仅产生β-肾上腺素能受体阻滞作用，以及高浓度（0.9微克/毫升）普萘洛尔预期产生额外的类似局部麻醉药的直接电生理效应时，对基础动作电位和早搏动作电位的影响。使用传统微电极技术对分离的犬心脏浦肯野纤维和心室肌纤维进行了检查。低浓度普萘洛尔对两种纤维类型均未产生明显的电生理变化。在恒定的基础周期长度下，高浓度普萘洛尔缩短了动作电位时程和不应期，同时降低了浦肯野纤维和心室肌纤维的最大除极速度（Vmax）。在浦肯野纤维中，高浓度普萘洛尔还减慢了动作电位时程恢复的动力学（tau c从124.6±6.5毫秒变为201.4±16.0毫秒，p<0.01，n = 7），减慢了Vmax的恢复动力学，并使两种纤维类型的标准化恢复曲线的早期部分向更长的动作电位时程值偏移。高浓度普萘洛尔使浦肯野纤维和心室肌纤维早搏动作电位时程范围（定义为恢复的前100毫秒内动作电位时程的差异）分别降低了39.5%和33.9%。这些发现表明：（a）低浓度普萘洛尔未产生直接电生理效应；（b）高浓度普萘洛尔除了先前报道的对Vmax和动作电位时程的影响外，还产生了几种潜在的抗心律失常作用。
