Effects of metoprolol on sympathetic remodeling and electrical remodeling at infarcted border zone after myocardial infarction in rabbits.
BACKGROUND
The findings of sympathetic remodeling and its electrophysiological implications force us to rerecognize the drugs presently used. The aim of this study was to investigate the effects of metoprolol on sympathetic remodeling and electrical remodeling at the infarcted border zone (IBZ) after myocardial infarction (MI).


METHODS
Forty rabbits were randomly assigned into two groups: MI group (n = 20), ligation of the anterior descending coronary; Metoprolol group (n = 20), ligation of the anterior descending coronary and administration of oral metoprolol 5 mg/kg/day. Eight weeks after surgery, transmural dispersion of repolarization (TDR) at baseline, TDR and difference of TDR (deltaTDR) during sympathetic nerve stimulation were measured at the IBZ. The distribution and densities of growth associated protein 43 and tyrosine hydroxylase positive nerves at the IBZ were detected with immunohistochemical techniques.


RESULTS
The study was completed in the 36 surviving animals (18 rabbits in each group). The densities of growth associated protein 43 and tyrosine hydroxylase positive nerves in the Metoprolol group (2,550 +/- 554 and 1,779 +/- 458 microm2/mm2, respectively) were lower than in the MI group (3,217 +/- 589 and 2,616 +/- 528 microm2/mm2, respectively; both p < 0.01). TDR at baseline, TDR and deltaTDR during sympathetic nerve stimulation were shorter in the Metoprolol group than in the MI group (p < 0.01 for all).


CONCLUSIONS
Metoprolol can inhibit sympathetic remodeling and electrical remodeling at the IBZ after MI. The association of metoprolol with improved electrical remodeling may be partly related to the inhibition of sympathetic remodeling.
Jiang
Hong
H
Department of Cardiology, Renmin Hospital of Wuhan University, Wuchang, Wuhan, China. hong_j_wurm@163.com
Lu
Zhibing
Z
Yu
Ying
Y
Zhao
Dongdong
D
Jian
Xiaoli
X
Yang
Bo
B
Huang
Congxin
C
D000200:Action Potentials / Q000187:drug effects*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D005260:Female; D019922:GAP-43 Protein / Q000096:biosynthesis; D006321:Heart / Q000294:innervation; D007150:Immunohistochemistry; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D000319:Adrenergic beta-Antagonists; D019922:GAP-43 Protein; D014446:Tyrosine 3-Monooxygenase; D008790:Metoprolol