Low-dose carvedilol reduces transmural heterogeneity of ventricular repolarization in congestive heart failure

Authors: ZHONG, Jiang-hua; CHEN, Xiao-pan¹; YUN, Mei-ling¹; LI, Wei-jing¹; CHEN, Yan-fang²; YAO, Zhen

Source: Acta Pharmacologica Sinica, Volume 28, Number 8, August 2007 , pp. 1161-1165(5)

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Abstract:

Aim: To study the effects of carvedilol on the transmural heterogeneity of ventricular repolarization in rabbits with congestive heart failure (CHF). Methods: Rabbits were randomly divided into 3 groups: control, CHF and carvedilol treated CHF group. Monophasic action potential duration (MAPD) in the 3 myocardial layers was simultaneously recorded. Results: All the rabbits in the CHF group had signs of severe CHF. Compared with the control group, the mean blood pressure and cardiac output were significantly decreased, while peripheral resistance was significantly increased in the CHF group. This proved that the CHF model was successful created with adriamycin in this study. Compared to the control group, the ventricular fibrillation threshold (VFT) was remarkably decreased and all MAPD of the 3 myocardial layers were extended in rabbits with CHF. However, the extension of MAPD in the midmyocardium was more obvious. The transmural dispersion of repolarization (TDR) was significantly increased in CHF. Low-dose carvedilol (0.25 mg/kg, twice daily) had no effects on ventricular remodeling. Treatment with low-dose carvedilol significantly increased VFT. Although the MAPD of the 3 myocardial layers were further prolonged in the carvedilol treated CHF group, the prolongation of MAPD in the midmyocardium was shorter than those in the epicardium and endocardium. Treatment with low-dose carvedilol significantly decreased TDR in CHF. Conclusion: In the present study, the transmural heterogeneity of ventricular repolarization increased in the rabbits with CHF. Low-dose carvedilol decreased the transmural heterogeneity of ventricular repolarization in CHF, which may be related to its direct electrophysiological property rather than its effect on ventricular remodeling.

Keywords: carvedilol; congestive heart failure; midmyo-cardium; monophasic action potential duration; repolarization

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2007.00613.x

Affiliations: 1: Department of Cardiology, Affiliated Hospital of Hainan Medical College, Haikou 570102, China 2: Department of Pharmacology and Toxicology, Wright State University, Ohio 45435, USA

Publication date: 2007-08-01

Low-dose carvedilol reduces transmural heterogeneity of ventricular repolarization in congestive heart failure

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