[Effects of pretreatment with metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization in rats].
OBJECTIVE
To investigate the effects of metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization(CME) in rats.


METHODS
Adult rats were randomly assigned into CME group (intraventricular injection of 3000 microspheres with 42 µm in diameter), sham-operated group (0.1 ml saline) and CME plus metoprolol group (pretreatment with 3 bolus metoprolol 2.5 mg/kg intravenous injection at 10 minutes interval at 30 minutes before microspheres injection, n = 15, each group). Cardiac function was evaluated by echocardiography at 6 hours post various treatments. Cardiomyocyte apoptosis was detected with TUNEL staining and the expression of caspase-3 and caspase-8 was detected with Western blot analysis.


RESULTS
Compared with sham-operated group, LVEF (72.68% ± 3.26% vs. 82.64% ± 3.43%, P < 0.05), fractional shortening (FS) (37.46% ± 2.38% vs. 42.85% ± 3.25%) and cardiac output (CO) [(0.101 ± 0.006) L/min vs. (0.162 ± 0.008) L/min] were significantly reduced while left ventricular end-diastolic diameter (LVEDd) [(6.22 ± 0.17) mm vs. (5.18 ± 0.43) mm] was significantly increased in CME group (all P < 0.05). Cardiac function [LVEF:73.94% ± 4.22%, FS:38.53% ± 2.03%, CO:(0.120 ± 0.012) L/min, LVEDd:(6.18 ± 0.27) mm] was similar in CME plus metoprolol group compared to CME group (all P > 0.05). The cardiomyocytes apoptosis rates (3.19% ± 1.23% vs. 0.18% ± 0.10%) and the levels of activated caspase-3 and caspase-8 proteins were significantly increased in CME group than in sham-operated group (all P < 0.05). The cardiomyocyte apoptosis rate (1.32% ± 0.28%) and the levels of activated caspase-3 and caspase-8 proteins were significantly lower in CME plus metoprolol group than in CME group (all P < 0.05).


CONCLUSIONS
Metoprolol pretreatment reduced post-CME myocardial apoptosis possibly through downregulating death receptor-mediated apoptotic pathway.
Department of Cardiology, First Affiliated Hospital of Guangxi Medical University,Nanning 530021, China.
Qiang
Q
Su
Lang
L
Li
You
Y
Zhou
Jiang-you
JY
Wang
Wei-ming
WM
Wen
Yong-guang
YG
Lu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000378:metabolism*; D054059:Coronary Occlusion / Q000188:drug therapy; D004195:Disease Models, Animal; D004617:Embolism / Q000188:drug therapy; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
C505528:Casp8 protein, rat; D053181:Caspase 8; D008790:Metoprolol