© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Altered response to ibutilide in a heart failure model
Division of Cardiovascular Disease, Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN, USA
* Corresponding author. Cardiology Division, UHN-62 Oregon Health Sciences University 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA. Tel.: +1-503-494-8750; fax: +1-503-494-8550 chughs{at}ohsu.edu
Objective: Despite the frequent use of anti-arrhythmic drugs in the general population, the electrophysiologic effects of these agents have not been elucidated in congestive heart failure (CHF). Methods: To examine the impact of left ventricular dysfunction on actions of type III anti-arrhythmic drugs, we evaluated the actions of ibutilide in a canine model of pacing-induced dilated cardiomyopathy. Following ablation of the atrioventricular node, effects on action potential duration at 90% (APD90) were compared in vivo, between eight CHF animals and seven controls. Monophasic action potential recordings were obtained from right and left ventricular endocardium/epicardium during and after three doses of ibutilide (0.01, 0.02 and 0.05 mg/kg), at pacing cycle lengths of 300–1000 ms. Results: APD90 prolongation with ibutilide (0.01 mg/kg) was significantly greater in CHF vs. controls (P = 0.0026, ANOVA). However, plasma ibutilide levels at this dose, were not significantly different between the two groups. In CHF, maximal effects were observed at the lowest dose, whereas effects were gradual and dose-dependent in controls. With ibutilide administration (0.01 mg/kg), an increased dispersion of left–right ventricular APD90 was observed in CHF, but not in controls (P = 0.03). A trend was observed, for increased incidence of non-sustained polymorphic ventricular tachycardia in CHF. Conclusions: In the presence of CHF, the actions of ibutilide are altered significantly. These findings may reflect altered tissue effects, as a consequence of myocardial electrical remodeling in CHF.
KEYWORDS Antiarrhythmic agents; Heart failure; K-channel; Remodeling; Ventricular arrhythmias
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