Vos M A, Gorgels A P, Leunissen J D, van der Nagel T, Halbertsma F J, Wellens H J
Department of Cardiology, University Hospital, Maastricht, The Netherlands.
J Cardiovasc Pharmacol. 1992 May;19(5):682-90.
In conscious dogs with chronic atrioventricular (AV) block, we recently demonstrated that flunarizine is effective against ouabain-induced arrhythmias (triggered activity resulting from delayed afterdepolarizations, DADs) but fails to suppress spontaneous ventricular tachycardias (VT) occurring 24 h after left anterior descending coronary artery occlusion (abnormal automaticity). Neither does flunarizine affect normal automaticity, which suggests that flunarizine could be used as a clinical tool to recognize cardiac arrhythmias based on triggered activity. To elucidate further the arrhythmia mechanism-specific action of flunarizine, we investigated (a) its hemodynamic and electrophysiologic effects in 6 anesthetized dogs, (b) its ability to prevent pacing-induced VT 7 days after myocardial infarction (reentry) in 9 anesthetized animals, and (c) its effect on premature escape beats (PEBs) in 9 conscious dogs with chronic AV block. PEBs are probably caused by DADs. Flunarizine decreased systemic blood pressure (p less than 0.01), and left ventricular dP/dt (p less than 0.01), but did not affect AH or HV internal, QRS duration, QT time, or the effective refractory period of either AV node or right ventricle over a wide range of (paced) cycle lengths. Flunarizine decreased the inducibility of PEBs by 42% (p less than 0.01), but not that of the reentrant VT in any of the 6 inducible dogs. Therefore, we conclude that although flunarizine has no electrophysiologic effects in normal heart, it prevents induction of PEBs. The inability of flunarizine to prevent induction of reentrant VT confirms the mechanism-specific action of flunarizine against triggered activity.
在清醒的慢性房室（AV）传导阻滞犬中，我们最近证实氟桂利嗪对哇巴因诱发的心律失常（由延迟后除极，即DADs引起的触发活动）有效，但不能抑制左前降支冠状动脉闭塞24小时后出现的自发性室性心动过速（VT，异常自律性）。氟桂利嗪也不影响正常自律性，这表明氟桂利嗪可作为一种临床工具，用于识别基于触发活动的心律失常。为了进一步阐明氟桂利嗪对心律失常机制的特异性作用，我们研究了：（a）其对6只麻醉犬的血流动力学和电生理作用；（b）其在9只麻醉动物中预防心肌梗死后7天起搏诱发的VT（折返）的能力；（c）其对9只清醒慢性AV阻滞犬的早搏逸搏（PEBs）的作用。PEBs可能由DADs引起。氟桂利嗪降低了体循环血压（p<0.01）和左心室dP/dt（p<0.01），但在较宽的（起搏）周期长度范围内，不影响AH或HV间期、QRS时限、QT间期，或房室结或右心室的有效不应期。氟桂利嗪使PEBs的诱发率降低了42%（p<0.01），但在6只可诱发的犬中，对折返性VT的诱发率没有影响。因此，我们得出结论，尽管氟桂利嗪在正常心脏中没有电生理作用，但它能预防PEBs的诱发。氟桂利嗪不能预防折返性VT的诱发，证实了氟桂利嗪对触发活动的机制特异性作用。
