Antiarrhythmic and Hemodynamic Actions of Flecainide Acetate (R-818) in the Ischemic Porcine Heart

The haemodynamic effect of intravenous flecainide acetate in patients with coronary artery disease.

“…Since no significant increase in difference between Vmax (control) and Vmax (flecainide) could be demonstrated at higher paced heart rate, it might be argued that the drug had no additional depressant effect on left ventricular performance at an increasing level of stress ( Figure 6). In the anaesthetized pig a negative inotropic action on the myocardium was observed following 2 mg/kg flecainide intravenously as stroke volume decreased, while pre-and afterload were not affected and max LV dP/dt decreased by 20% (Verdouw et al, 1979 stroke index and max LV dP/dt were observed. It is thus reasonable to assume that the decrease in the stroke index in this study is at least partly due to a slight negative inotropic effect of flecainide, although one must also take into account that the systemic vascular resistance was elevated.…”

“…In their experimental study in pigs, Verdouw et al (1979) demonstrated that flecainide did not modify the degree of ischaemia and that the ischaemic heart could tolerate the administration of a dose of 2 mg/kg without additional depression of overall left ventricular function. However in the present study, one patient on flecainide experienced angina at a lower paced heart rate than during the control APST.…”

“…It is thus reasonable to assume that the decrease in the stroke index in this study is at least partly due to a slight negative inotropic effect of flecainide, although one must also take into account that the systemic vascular resistance was elevated. In the forementioned experimental study (Verdouw et al, 1979) The negative inotropic effect and the slight increase in peripheral vascular resistance may be undesired in patients with severe ischaemic heart disease or those suffering from a myocardial infarction and a failing heart. It therefore appears advisable to administer the drug at a rate much slower than 0.2 mg/kg/min in patients at risk in order to avoid these acute haemodynamic changes related to the initial high plasma levels.…”

Effects of Flecainide Acetate on Ventricular Tachyarrhythmia and Fibrillation in Dogs with Recent Myocardial Infarction

“…In nonischemic anesthetized dogs, however, flecainide failed to alter consistently either traditional ventricular fibrillation threshold values or ventricular fibrillation thresholds following premature complexes [Hodess et al, 1979]. In anesthetized pigs, flecainide reduced the incidence of ventricular ectopic complexes, tachycardia and ventricular fibrillation during myocardial ischemia caused by the partial occlusion of the left anterior descending coronary artery, whereas the drug failed to reduce both the time to development or incidence of isch emic ventricular fibrillation following com plete occlusion of the distal left anterior de scending coronary artery [Verdouw et al, 1979]. It is noteworthy that the experimental antiarrhythmic evaluations of flecainide ace tate reviewed above were conducted in the absence of previous myocardial injury.…”

“…Flecainide acetate has been shown effective in suppressing a variety of experimentally induced ventricular dysrhythmias in animals [Schmid et al, 1975;Verdouw et al, 1979], and in suppressing ventricular premature de polarizations in man in several independent investigations [see Nappi and Anderson, 1985;Somberg and Tepper, 1986 for re views], Few preclinical or clinical studies, however, have examined the efficacy of fle cainide acetate in preventing ventricular ta chyarrhythmias or, more importantly, ven tricular fibrillation in the setting of recent myocardial ischemic injury.…”