Lynch J J, DiCarlo L A, Montgomery D G, Lucchesi B R
Department of Pharmacology, University of Michigan Medical School, Ann Arbor.
Pharmacology. 1987;35(4):181-93. doi: 10.1159/000138310.
The antiarrhythmic and antifibrillatory actions of the class IC antiarrhythmic agent flecainide acetate were examined in urethane-anesthetized dogs with recent myocardial infarction. The intravenous administration of flecainide in a loading dose of 1.0 mg/kg (n = 7) or 2.0 mg/kg (n = 6), followed by a maintenance infusion of 1.0 mg/kg/h to achieve plasma drug concentrations considered clinically therapeutic, failed to significantly elevate the electrical threshold current required to provoke ventricular fibrillation at infarct zone, border zone and non-infarct zone stimulation sites in postinfarction dogs. In 8 dogs which responded to baseline programmed stimulation with inducible sustained ventricular tachycardia, flecainide administered as 1.0 or 2.0 mg/kg loading doses followed by a 1.0 mg/kg/h maintenance infusion failed to prevent ventricular tachycardia initiation in any animal tested, although the post-treatment ventricular tachycardia cycle lengths were prolonged compared to baseline values (pre: 178 +/- 11 ms vs post: 202 +/- 17 ms, p less than 0.05). Flecainide administration apparently facilitated the induction of newly sustained ventricular tachycardia in 3 previously noninducible postinfarction dogs. The development of acute posterolateral ischemia at a site remote from previous anterior myocardial infarction resulted in the development of ventricular fibrillation in 4 of 11 (36%) saline-treated postinfarction dogs vs a cumulative 10 of 12 (83%) flecainide-treated, baseline noninducible postinfarction dogs (p less than 0.05 vs saline-treated). The incidence of sudden ischemic ventricular fibrillation was 7 of 7 (100%) among flecainide-treated baseline inducible postinfarction dogs. These data suggest that flecainide acetate may have only limited efficacy in preventing ventricular tachycardia or ventricular fibrillation soon after myocardial infarction.
在近期发生心肌梗死的乌拉坦麻醉犬中，研究了Ic类抗心律失常药物醋酸氟卡尼的抗心律失常和抗纤颤作用。静脉给予负荷剂量为1.0mg/kg（n = 7）或2.0mg/kg（n = 6）的醋酸氟卡尼，随后以1.0mg/kg/h的维持输注量给药，以达到临床治疗所需的血浆药物浓度，但未能显著提高梗死后犬梗死区、边缘区和非梗死区刺激部位诱发心室颤动所需的电阈值电流。在8只对基线程序刺激有可诱导的持续性室性心动过速反应的犬中，给予1.0或2.0mg/kg负荷剂量的醋酸氟卡尼，随后以1.0mg/kg/h的维持输注量给药，在任何受试动物中均未能预防室性心动过速的发作，尽管治疗后室性心动过速的周期长度与基线值相比有所延长（治疗前：178±11ms，治疗后：202±17ms，p<0.05）。醋酸氟卡尼给药显然促进了3只先前不可诱导的梗死后犬中新的持续性室性心动过速的诱发。在先前前壁心肌梗死部位以外的部位发生急性后外侧缺血，导致11只接受生理盐水治疗的梗死后犬中有4只（36%）发生心室颤动，而12只醋酸氟卡尼治疗的、基线不可诱导的梗死后犬中有10只（83%）发生心室颤动（与生理盐水治疗组相比，p<0.05）。在醋酸氟卡尼治疗的基线可诱导的梗死后犬中，缺血性室颤的发生率为7只中的7只（100%）。这些数据表明，醋酸氟卡尼在心肌梗死后不久预防室性心动过速或心室颤动方面可能只有有限的疗效。
