TY - JOUR
T1 - Altered response to ibutilide in a heart failure model
AU - Chugh, Sumeet S.
AU - Johnson, Susan B.
AU - Packer, Douglas L.
N1 - Funding Information:
This study was supported by the Mayo Foundation Clinical Investigator Program (Douglas L. Packer). The authors thank Pharmacia & Upjohn for their assistance in obtaining ibutilide levels.
PY - 2001
Y1 - 2001
N2 - 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. (C) 2001 Elsevier Science B.V.
AB - 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. (C) 2001 Elsevier Science B.V.
KW - Antiarrhythmic agents
KW - Heart failure
KW - K-channel
KW - Remodeling
KW - Ventricular arrhythmias
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U2 - 10.1016/S0008-6363(00)00235-2
DO - 10.1016/S0008-6363(00)00235-2
M3 - Article
C2 - 11121800
AN - SCOPUS:0034747793
SN - 0008-6363
VL - 49
SP - 94
EP - 102
JO - Cardiovascular research
JF - Cardiovascular research
IS - 1
ER -