Carvedilol ameliorates sympathetic nerve sprouting and electrical remodeling after myocardial infarction in rats.

Abstract

BACKGROUND:

We hypothesized that carvedilol, a nonselective β-blocker, can exert antiarrhythmogenic effects by inhibiting sympathetic nerve sprouting and electrical remodeling at peri-infarct zones after myocardial infarction (MI).

METHODS:

MI was induced by ligation of the coronary artery. The rats in the carvedilol group received 5.0mg/kg carvedilol twice a day. Eight weeks after MI, monophasic action potential duration (MAPD), effective refractory period (ERP) and the inducibility of ventricular arrhythmia at the peri-infarct zones were evaluated and compared with MI rats. After these studies, the expression of growth associated protein 43 (GAP43) and tyrosinehydroxylase (TH) at the peri-infarct zones were examined by western blot and RT-PCR analysis.

RESULTS:

Eight weeks after surgery, carvedilol shortened the duration of the MAPD determined as 20% (MAPD(20)) and 90% (MAPD(90)) repolarization time (33 ± 9 ms and 110 ± 18 ms vs 21 ± 6 ms and 76 ± 13 ms, both P<0.05) and ERP (76 ± 15 ms vs 62 ± 12 ms, P<0.05), respectively. Carvedilol decreased the inducibility of ventricular arrhythmia after MI (76% vs 32%, P<0.05). The expression of GAP43 and TH were suppressed by carvedilol after MI.

CONCLUSION:

Carvedilol exerts antiarrhythmogenic effects by ameliorating sympathetic nerve sprouting and electrical remodeling in MI rats. The effects of carvedilol on amelioration of electrical remodeling may be partly related to the inhibition of sympathetic remodeling.

• Authors: Huazhi Wen, Hong Jiang, Zhibing Lu, Xiaorong Hu, Bo He, Qizhu Tang, Congxin Huang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 64 Issue 7 Pg. 446-50 (Sep 2010) ISSN: 1950-6007 [Electronic] France
• PMID: 20359859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier Masson SAS. All rights reserved.

Chemical References

• Adrenergic beta-Antagonists
• Carbazoles
• GAP-43 Protein
• Propanolamines
• RNA, Messenger
• Carvedilol
• Tyrosine 3-Monooxygenase

Topics

• Action Potentials
• Adrenergic beta-Antagonists (pharmacology)
• Animals
• Arrhythmias, Cardiac (metabolism, physiopathology)
• Autonomic Pathways (metabolism, physiopathology)
• Carbazoles (pharmacology)
• Carvedilol
• GAP-43 Protein (metabolism)
• Heart (innervation, physiopathology)
• Male
• Myocardial Infarction (drug therapy, metabolism, physiopathology)
• Propanolamines (pharmacology)
• RNA, Messenger (metabolism)
• Random Allocation
• Rats
• Rats, Wistar
• Sympathetic Nervous System (drug effects, physiopathology)
• Tyrosine 3-Monooxygenase (metabolism)
• Ventricular Remodeling (drug effects)