In Vivo Electropharmacological Effects of Amiodarone and Candesartan on Atria of Chronic Atrioventricular Block Dogs

Abstract

Abstract. Electropharmacological effects of chronically administered amiodarone and candesartan on atria that had been remodeled against congestive heart failure were assessed using dogs (about 10 kg in weight) with chronic atrioventricular block. Amiodarone was administered orally in a dose of 200 mg / body per day for the initial 7 days followed by 100 mg for the following 21 days (n = 7). Candesartan was administered in a dose of 12 mg / body per day for 28 days (n = 7). All animals survived the 4-week experimental period, indicating the lack of risks for inducing cardiohemodynamic collapse or torsade de pointes by these drugs. The plasma amiodarone concentration was 353 ng / ml at 4 weeks of treatment. Before candesartan treatment (control), intravenous administration of 30 ng / kg of angiotensin II increased the mean blood pressure by 18 mmHg, which was significantly decreased to 1 mmHg by 4 weeks of treatment. Amiodarone prolonged the atrial effective refractory period without affecting inter-atrial conduction time and decreased the duration of the burst pacing-induced atrial fibrillation, whereas candesartan hardly affected these variables. These results indicate that amiodarone should become a pragmatic pharmacological strategy against atrial fibrillation in patients with chronically compensated heart failure and suggest that a much higher dose of candesartan may be needed to exert its efficacy in this model.

Impacts of Surgically Performed Renal Denervation on the Cardiovascular and Electrophysiological Variables in the Chronic Atrioventricular Block Dogs – Comparison With Those of Amiodarone Treatment –

“…reported to possess the structural and electrophysiological remodeling that may promote the occurrence and maintenance of atrial fibrillation. 16,[18][19][20] In this study, amiodarone prolonged the AERP, which supports the clinical efficacy of amiodarone in preventing the recurrence of atrial fibrillation. 24 In contrast, renal denervation was reported to reduce the duration of rapid pacing-induced atrial fibrillation in the pig, by which the AERP and P-wave duration were hardly affected.…”

Simultaneous Assessment of Pharmacokinetics of Pilsicainide Transdermal Patch and Its Electropharmacological Effects on Atria of Chronic Atrioventricular Block Dogs

“…Thus, a new formulation of pilsicainide that can maintain optimal plasma drug concentration for a longer period may theoretically increase its utility and efficacy as an antiarrhythmic drug. Since we recently developed a novel transdermal patch containing pilsicainide, we simultaneously assessed the pharmacokinetics of the pilsicainide transdermal patch and its electropharmacological profile using the canine chronic atrioventricular block model (8). Previous studies have indicated that this model has a pathophysiology of chronically compensated heart failure together with the increase of sympathetic tone and the stretch activating paradigm of atria and ventricles, leading to fibrosis and conduction abnormalities that may promote the occurrence and maintenance of atrial fibrillation as well as ventricular arrhythmias (9 -11).…”