Woosley R L, Kornhauser D, Smith R, Reele S, Higgins S B, Nies A S, Shand D G, Oates J A
Circulation. 1979 Oct;60(4):819-27. doi: 10.1161/01.cir.60.4.819.
The antiarrhythmic efficacy of propranolol was evaluated in 32 patients with chronic high frequency ventricular arrhythmias in a placebo-controlled protocol. After a placebo control period, propranolol was begun and the dosage increased sequentially until arrhythmia suppression was achieved, side effects appeared, or a maximum dosage of 960 mg/day was reached. Computerized analysis of ambulatory recordings was used to quantify the arrhythmias. Twenty-four patients had 70--100% arrhythmia suppression at plasma levels ranging from 12--1100 ng/ml (end of dosing interval). Eight patients in this group had frequent episodes of ventricular tachycardia that were totally suppressed at or below the dosage that produced greater than or equal to 70% suppression of ventricular ectopic depolarizations (VEDs). A biphasic dose-response curve was seen in five patients who responded with a decrease in arrhythmia frequency in the lower ranges of dosages but had increased frequency of ectopic rhythms as the dosage was increased above the optimal level. Only one-third of patients responded at doses less than or equal to 160 mg/day. However, with dosages of 200--640 mg/day, an additional 40% responded. Propranolol appears to control ventricular arrhythmias safely and effectively in many patients. The finding that the antiarrhythmic effect in many patients required plasma concentrations greater than those that produce substantial beta-adrenergic blockage raises a question whether blockade of cardiac beta receptors can directly account for all of the antiarrhythmic actions of propranolol.
在一项安慰剂对照试验中,对32例慢性高频室性心律失常患者评估了普萘洛尔的抗心律失常疗效。经过安慰剂对照期后,开始使用普萘洛尔并依次增加剂量,直至心律失常得到抑制、出现副作用或达到960毫克/天的最大剂量。采用动态心电图记录的计算机分析来量化心律失常。24例患者在血浆浓度为12 - 1100纳克/毫升(给药间隔末期)时心律失常抑制率达70% - 100%。该组中有8例频繁发作室性心动过速的患者,在产生大于或等于70%室性异位去极化(VEDs)抑制作用的剂量及以下时,室性心动过速完全被抑制。在5例患者中观察到双相剂量反应曲线,这些患者在较低剂量范围内心律失常频率降低,但当剂量增加到最佳水平以上时,异位节律频率增加。只有三分之一的患者在剂量小于或等于160毫克/天时出现反应。然而,在剂量为200 - 640毫克/天时,又有40%的患者出现反应。普萘洛尔似乎能在许多患者中安全有效地控制室性心律失常。许多患者的抗心律失常作用所需血浆浓度高于产生显著β - 肾上腺素能阻滞作用的浓度,这一发现提出了一个问题,即心脏β受体的阻滞是否能直接解释普萘洛尔所有的抗心律失常作用。