Lathers C M
Eur J Pharmacol. 1980 Jun 13;64(2-3):95-106. doi: 10.1016/0014-2999(80)90032-1.
The purpose of this study was to determine the effect of the beta-blocking agent timolol on postganglionic cardiac and preganglionic splanchnic sympathetic and vagal neural discharge, ouabain-induced arrhythmia, heart rate and mean arterial blood pressure. Cats were anesthetized with alpha-chloralose, given atropine, and pretreated with timolol (5 mg/kg, i.v. infused at a rate of 0.5 mg/kg/min for 10 min). Bolus injections of ouabain (25 microgram/kg, i.v.) were given every 15 min until the animals died; the first injection was given 15 min after the end of the timolol infusion. When compared with cats (n = 13) receiving only ouabain, timolol (n = 11 cats) increased the time to ouabain-induced arrhythmia and death from 23 +/- 3 to 48 +/- 7 and 46 +/- 3 to 76 +/- 9 min, respectively (p less than 0.05). Both heat rate and mean arterial blood pressure had decreased from 137 +/- 4 to 104 +/- 6 beats/min and 133 +/- 6 to 103 +/- 7 mm Hg, respectively (P less than 0.05); ouabain did not reverse the decreases. Neural activity monitored from the vagus and from the postganglionic cardiac and preganglionic splanchnic sympathetic nerves was not significantly altered by the infusion of timolol. The administration of ouabain after timolol did not alter splanchnic nor vagal discharge. Most important was the observation that postganglionic cardiac sympathetic neural discharge exhibited both increases and decreases, i.e., a nonuniform neural discharge, at the time of ouabain-induced arrhythmia and that the ouabain-induced nonuniformity did not occur in the cats pretreated with timolol. Thus, the protective effect of timolol may be due, in part, to prevention of the nonuniform postganglionic cardiac sympathetic neural discharge and to the prevention of ouabain-induced increases in vagal discharge. The establishment of beta-blockade and a direct negative inotropic action may also have contributed to the antiarrhythmic action of timolol.
本研究的目的是确定β受体阻滞剂噻吗洛尔对节后心脏、节前内脏交感神经和迷走神经放电、哇巴因诱发的心律失常、心率和平均动脉血压的影响。猫用α-氯醛糖麻醉，给予阿托品，并预先用噻吗洛尔（5mg/kg，静脉注射，以0.5mg/kg/min的速率输注10分钟）进行预处理。每15分钟静脉推注一次哇巴因（25μg/kg），直至动物死亡；第一次注射在噻吗洛尔输注结束后15分钟进行。与仅接受哇巴因的猫（n = 13）相比，噻吗洛尔（n = 11只猫）使哇巴因诱发心律失常和死亡的时间分别从23±3分钟增加到48±7分钟以及从46±3分钟增加到76±9分钟（p<0.05）。心率和平均动脉血压分别从137±4次/分钟降至104±6次/分钟以及从133±6mmHg降至103±7mmHg（P<0.05）；哇巴因并未逆转这些下降。从迷走神经、节后心脏交感神经和节前内脏交感神经监测到的神经活动并未因噻吗洛尔的输注而发生显著改变。在噻吗洛尔给药后给予哇巴因并未改变内脏或迷走神经放电。最重要的观察结果是，在哇巴因诱发心律失常时，节后心脏交感神经放电既增加又减少，即神经放电不均匀，而在用噻吗洛尔预处理的猫中未出现哇巴因诱发的不均匀性。因此，噻吗洛尔的保护作用可能部分归因于预防节后心脏交感神经放电不均匀以及预防哇巴因诱发的迷走神经放电增加。β受体阻滞的建立和直接负性肌力作用也可能对噻吗洛尔的抗心律失常作用有贡献。
