In vivo and in vitro electrophysiologic effects of terodiline on dog myocardium.
In vivo and in vitro electrophysiologic effects of terodiline on dog myocardium.
复制标题
特罗地林对狗心肌的体内和体外电生理作用。
DOI：
10.1111/j.1540-8167.1995.tb00418.x
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发表时间：
1995
影响因子：
2.7
通讯作者：
Zipes,DP
中科院分区：
文献类型：
--
作者：
Pressler,ML;Warner,MR;Rubart,M;Rardon,DP;Zipes,DP
特罗地林的电生理效应。简介：特罗地林被广泛用于治疗尿失禁，据报道可引起心动过缓和尖端扭体。方法和结果：在本研究中，我们表征了特罗地林在活体犬心脏组织和离体犬心脏浦肯野纤维中的电生理作用。特地地林(1~10μM)可剂量依赖性地降低动作电位波幅和最大上搏速度(Vmax)。这些效应的阈值是∼2μM(0.6 mg/L)，且这种变化具有周期依赖性。特罗地林(≥2μM)也能抑制动作电位平台，但在≤10μM浓度下对动作电位时程无明显影响。体内实验表明，大剂量特罗地林(3 mg/kg)可延长AH和HV间期，减慢自发窦性心率，延长心室不应期，并抑制迷走神经诱发的窦房结减慢。交感神经对自发性窦性心率的影响不变。在离体犬和麻醉犬的浦肯野纤维上，特罗地林在正常或低钾条件下均不引起后除极、重复放电或室性快速性心律失常。结论：特罗地林(≤1~2μM)可阻断犬心肌组织的钠、钙通道和M受体。
Electrophysiologic Effects of Terodiline.Introduction:Terodiline hydrochloride, widely prescribed for urinary incontinence, has been reported to cause bradycardia and torsades de pointes.Methods and Results:In this study, we characterized the electrophysiologic effects of terodiline in dog cardiac tissues in vivo and in isolated canine cardiac Purkinje fibers. Terodiline (1 to 10 μM) resulted in dose‐dependent reduction of action potential amplitude and maximal upstroke velocity (Vmax). The threshold for these effects was ∼ 2 μM (0.6 mg/L), and the changes were cycle‐length dependent. Terodiline (≥ 2 μM) also depressed the action potential plateau but did not significantly alter action potential duration at concentrations ≤ 10 μM. In vivo studies demonstrated that high doses of terodiline (3 mg/kg) lengthened AH and HV intervals, slowed spontaneous sinus rate, prolonged ventricular refractoriness, and inhibited vagally induced slowing of the sinus node. Sympathetic effects on spontaneous sinus rate were unchanged. In both isolated canine Purkinje fibers and anesthetized dogs, terodiline did not evoke afterdepolarizations, repetitive firing, or ventricular tachyarrhythmias under normal or hypokalemic conditions.Conclusion: Our findings suggest that terodiline (≤ 1 to 2 μM) leads to blockade of sodium and calcium channels as well as muscarinic receptors in canine cardiac tissues.