Vos M A, Gorgels A P, Drenth J P, Leunissen J D, Wellens H J
Department of Cardiology, Academic Hospital Maastricht, University of Limburg, The Netherlands.
Eur J Pharmacol. 1989 Jun 8;165(1):139-45. doi: 10.1016/0014-2999(89)90780-2.
The ability of flunarizine to terminate ouabain-induced ventricular tachycardia was investigated in conscious dogs. These arrhythmias result from triggered activity based on delayed afterdepolarizations. Sustained ventricular tachycardia was induced by ouabain (48 +/- 6 micrograms/kg) and pacing in 13 animals with surgically induced complete atrioventricular block. Flunarizine was administered i.v. when the arrhythmia had persisted for at least 20 min. Flunarizine induced an increase of the R-R interval from 300 +/- 30 to 410 +/- 50 ms (P less than or equal to 0.001) in all dogs. Flunarizine (2 mg/kg) terminated ventricular tachycardia with long R-R intervals (330 +/- 20 ms) in seven dogs. An additional dose of flunarizine (1 mg/kg) resulted in termination of the faster tachycardias (280 +/- 15 ms). The arrhythmias were not induced again by pacing for 27 +/- 18 min. Reinitiated tachycardias could be suppressed again by flunarizine. In conclusion, flunarizine (1) slows and terminates arrhythmias resulting from delayed afterdepolarizations, and (2) prevents their reinitiation.
在清醒犬中研究了氟桂利嗪终止哇巴因诱发的室性心动过速的能力。这些心律失常是由基于延迟后除极的触发活动引起的。在13只手术诱导完全性房室传导阻滞的动物中,通过哇巴因(48±6微克/千克)和起搏诱发持续性室性心动过速。当心律失常持续至少20分钟时静脉注射氟桂利嗪。氟桂利嗪使所有犬的R-R间期从300±30毫秒增加到410±50毫秒(P≤0.001)。氟桂利嗪(2毫克/千克)使7只犬的长R-R间期(330±20毫秒)的室性心动过速终止。额外剂量的氟桂利嗪(1毫克/千克)导致更快的心动过速(280±15毫秒)终止。起搏27±18分钟未再次诱发心律失常。重新诱发的心动过速可再次被氟桂利嗪抑制。总之,氟桂利嗪(1)减慢并终止由延迟后除极引起的心律失常,(2)防止其再次发作。