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


CONCLUSIONS
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.
Wen
Huazhi
H
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, 238, Jiefang Road, Wuchang, Wuhan 430060, PR China.
Jiang
Hong
H
Lu
Zhibing
Z
Hu
Xiaorong
X
He
Bo
B
Tang
Qizhu
Q
Huang
Congxin
C
D000200:Action Potentials; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology; D017776:Autonomic Pathways / Q000378:metabolism / Q000503:physiopathology; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D019922:GAP-43 Protein / Q000378:metabolism; D006321:Heart / Q000294:innervation / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011412:Propanolamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D019922:GAP-43 Protein; D011412:Propanolamines; D012333:RNA, Messenger; D000077261:Carvedilol; D014446:Tyrosine 3-Monooxygenase