[Effects of early treatment with metoprolol on myocardial inflammatory cytokine expression and heart function in rats with acute myocardial infarction].
OBJECTIVE
The aim of study was to explore the effects of early beta-adrenergic blockade-metoprolol treatment on myocardial inflammatory cytokine expression and heart function in rats after acute myocardial infarction (AMI).


METHODS
The therapeutic effects of metoprolol on myocardial inflammation and heart function up to 4 weeks (according to the protocol of CCS-2) were studied by the rat model of AMI. Myocardial inflammation was examined by taking account of the number of lymphocytes infiltrated in the myocardium and analyzing the myocardial cytokine production including the pro-inflammatory cytokines: interleukin (IL)-1beta, 6 and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokine: IL-10. Echocardiography was used to evaluate heart function.


RESULTS
The levels of TNF-alpha, IL-1beta, IL-6 and IL-10 in AMI group were markedly elevated compared to sham rats (P < 0.01) and the cytokines principally excreted by cardiac myocytes. After 4 weeks therapy, metoprolol reduced the production of TNF-alpha and IL-1beta and increased IL-10 levels (P < 0.05) in cardiac myocytes, but had no effect on the number of lymphocytes infiltrated in myocardium. Echocardiography showed that metoprolol markedly improved left heart function (P < 0.05).


CONCLUSIONS
Early metoprolol treatment can improve heart function and myocardial inflammatory cytokine expression after AMI. One immunopharmacologic mechanism underlying the beneficial effects of beta-adrenergic blockade may involve the attenuation of pro-inflammatory cytokines and the increase of anti-inflammatory cytokine levels in cardiac myocytes.
Cheng
Xiang
X
Laboratory of Cardiovascular Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Liao
Yu-hua
YH
Li
Bin
B
Yang
Ya-li
YL
Zhang
Jin-ying
JY
Lu
Bao-jun
BJ
Ge
Hong-xia
HX
Liu
Ying
Y
Guo
Zhang-qiang
ZQ
Zhang
Ling
L
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D016207:Cytokines / Q000032:analysis* / Q000235:genetics; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D012333:RNA, Messenger; D008790:Metoprolol