Comparative effects of beta-adrenergic blocking drugs on experimental ventricular fibrillation threshold.
Comparative effects of beta-adrenergic blocking drugs on experimental ventricular fibrillation threshold.
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β-肾上腺素能阻滞药物对实验性心室颤动阈值的比较影响。
DOI：
10.1016/0002-9149(83)90368-5
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Green,LS
中科院分区：
文献类型：
--
作者：
Anderson,JL;Rodier,HE;Green,LS
最近的临床研究表明，某些β肾上腺素能阻断药物，如噻吗洛尔，可能会减少缺血性心脏病患者的猝死，但其机制尚未确定。为了评估和比较β受体阻滞药物作为预防猝死的潜在机制的抗纤维颤动作用，在静脉注射盐水溶液或3倍连续增量（0.003至1.0 mg/kg）的5种具有不同辅助特性的β受体阻滞药物期间，在冠状动脉缺血前后3分钟，测量麻醉、开胸犬的心室颤动（VF）阈值。在对照研究中，在非缺血状态下输送 11.7 ± 7.6 mA 的电流序列和在缺血状态下输送 7.0 ± 7.4 mA 的电流序列后，发生心室颤动 (n = 46)。所有 5 种 β 阻滞药物（盐水溶液除外）在非缺血（至 67 ± 30 mA）和缺血条件（至 42 ± 31 mA）下均导致 VF 阈值显着（平均 6 倍）增加（p < 0.001）。每种药物达到的最大 VF 阈值相似：噻吗洛尔，71、39 mA（非缺血、缺血条件，n = 10）：吲哚洛尔，81、46 mA（n = 7）；普萘洛尔，58.36 mA（n = 7）；美托洛尔，60、40 mA (n = 7)；和拉贝洛尔，67.52 mA (n = 6)。然而，首次出现最大效应的有效剂量（mg/kg）差异很大：噻吗洛尔，0.01 mg/kg；吲哚洛尔，0.1毫克/千克；普萘洛尔，0.3毫克/千克；美托洛尔，1.0毫克/公斤；和拉贝洛尔，1.0 mg/kg。抗纤维性颤动效力（mg/kg）通常与已知的β-阻滞效力比率相当，但噻吗洛尔的效力明显更高。星状神经节冲动的中断是室颤阈值增加的部分原因。因此，实验性阻断β-肾上腺素能药物会产生显着的抗纤维颤动作用。心室颤动阈值的增加被认为是一种可能的保护机制，β-受体阻滞药物可通过该机制减少猝死。
Recent clinical studies suggest that certain betaadrenergic blocking drugs, such as timolol, may reduce sudden death in patients with ischemic heart disease, but the mechanism has not been established. To assess and compare antifibrillatory effects of beta-blocking drugs as a potential mechanism of sudden death prevention, the ventricular fibrillation (VF) threshold was measured in anesthetized, open-chest dogs before and after 3 minutes of coronary ischemia during intravenous administration of saline solution or 3-fold serial increments (0.003 to 1.0 mg/kg) of 5 beta-blocking drugs with various accessory properties. Ventricular fibrillation occurred in control studies after delivery of a current train of 11.7 ± 7.6 mA in the nonischemic state and 7.0 ± 7.4 mA during ischemia (n = 46). All 5 betablocking drugs but not saline solution caused substantial (average 6-fold) increases (p < 0.001) in the VF threshold under both nonischemic (to 67 ± 30 mA) and ischemic conditions (to 42 ± 31 mA). The maximal VF thresholds attained were similar for individual drugs: timolol, 71, 39 mA (nonischemic, ischemic conditions, n = 10): pindolol, 81, 46 mA (n = 7); propranolol, 58,36 mA (n = 7); metoprolol, 60, 40 mA (n = 7); and labetolol, 67,52 mA (n = 6). The effective doses (mg/kg) at which maximal effects first occurred, however, varied widely: timolol, 0.01 mg/kg; pindolol, 0.1 mg/kg; propranolol, 0.3 mg/kg; metoprolol, 1.0 mg/kg; and labetolol, 1.0 mg/kg. The antifibrillatory potency (mg/kg) generally paralleled known ratios of beta-blocking efficacy, except for timolol's apparently greater potency. Interruption of stellate ganglionic impulses accounted for part of the augmentation in VF threshold. Thus, a substantial antifibrillatory effect accompanies experimental blockade of beta-adrenergics timuli. An increase in VF threshold is suggested as a possible protective mechanism by which beta-blocking drugs reduce sudden death.