Effects of acetyl strophanthidin on duration of atrial fibrillation in the neurally-intact and blockaded dog

Abstract

Although the inotropic and dromotropic effects of cardiac glycosides in atrial fibrillation (AF) are well recognized, their action on AF itself is not clear. Accordingly, to determine whether cardiac glycosides prolong AF, the duration of electrically induced AF, atrioventricular conduction, and left ventricular function were assessed for 30 minutes before and for 30 minutes following intravenous administration of acetyl strophanthidin (AS), 20 micrograms/kg, in neurally intact, beta-blocked, and beta-blocked and vagotomized dogs. In the intact dog, AS, 20 micrograms/kg, increased peak dp/dt by 132 +/- 35 mmHg.sec-1, p less than 0.05, and slowed ventricular response by 16 +/- 7 min-1, p less than 0.05, but had a variable effect on AF duration. While the increased left ventricular peak dp/dt persisted for 15 minutes after AS, an increased duration of AF was evident only at 20 minutes, when the effects of AS on left ventricular (LV) inotropy were no longer apparent. Moreover, the subset of dogs that did not demonstrate prolongation of average duration of AF after AS had a greater increment of peak dp/dt than those that showed prolongation, 237 +/- 52 versus 53 +/- 31 mmHg.sec-1, p less than 0.05. An additional 20 micrograms/kg, which produced ventricular extrasystoles, prolonged AF duration when compared to both control and 30-minute measurements. Acetyl strophanthidin, 20 micrograms/kg, had a variable effect on duration of AF with beta-blockade but prolonged duration by 114 +/- 34%, p less than 0.05, with both vagotomy and beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

The relation of quinidine-Induced elevation of serum digoxin concentration to the conversion of atrial fibrillation-flutter: A pilot study

“…In a randomized, placebo-controlled trial of patients with atrial fibrillation and normal left ventricular function, digoxin did not increase the number of conversions to sinus rhythm; moreover, in that study SDC was higher than the levels found in this investigation [3]. However, two experimental studies in dogs [4][5], one of which showed a relation between the conversion of atrial fibrillation to the inotropic actions of acetyl strophanthidin I5], an electrophysiologic study in humans [6], and several clinical trials demonstrating the efficacy of prophylactic digoxin in preventing postoperative atrial fibrillation indicate that the controversy is still not resolved. In any case, when digoxin and quinidine are used in the treatment of atrial fibrillation or flutter, elevation of SDC by quinidine does not appear to play an important role in the return to sinus rhythm.…”

Effects of Cardiac Glycosides on Atrial Contractile Dysfunction After Short-term Atrial Fibrillation

“…36 Previously, we have found a lack of benefit of AS on the duration of AF induced by short bursts of rapid atrial stimulation. 27 Those investigations also demonstrated a prolongation of AF at toxic dosages of AS, 27 effects that can be explained by the intense neurohumoral actions including sympathetic effects, 26 and by the delayed afterdepolarizations (oscillations) that occur with excessive amounts of cardiac glycosides. 37 Because atrial hypocontractility following AF is associated with reduced calcium transients, 17 the direct cellular action of cardiac glycosides, which increases cytosolic calcium, 38 could explain the favorable action of AS on atrial stunning.…”

“…To assess the effects of cardiac glycosides on post-AF atrial stunning, a model of AF, rapid atrial electrical stimulation for 5 min, which has been shown to produce transient atrial contractile dysfunction, 15,20 was used, and acetylstrophanthidin (AS), a cardiac glycoside with a time of action overlapping with the development of these abnormalities, 27 was administered. Experiments were performed under neurally intact and autonomically blockaded conditions, and the effects of the glycoside were determined both with baseline conditions already influenced by AS and under conditions without use of the drug.…”