Effect of metoprolol on myocardial apoptosis and caspase-9 activation after coronary microembolization in rats.
OBJECTIVE
To explore the effect of metoprolol on myocardial apoptosis and caspase-9 activation after coronary microembolization (CME) in rats.


METHODS
Forty rats were randomly divided into four groups (n=10 each): a sham operation (control) group, CME plus saline (CME) group, CME plus metoprolol (metoprolol) group and caspase-9 inhibitor Z-LEHD-FMK (ZLF) group. CME was induced by injecting 3000 polyethylene microspheres (42 μm diameter) into the left ventricle during a 10 s occlusion of the ascending aorta. Echocardiography, terminal deoxynucleotidyl transferase dUTP nick end labelling and Western blotting were used to evaluate cardiac function, apoptosis and activation of caspase-9/caspase-3, respectively, 6 h after CME.


RESULTS
The echocardiographic parameters of left ventricular function were significantly decreased in the CME group compared with the control group (P<0.05); however, the metoprolol group and ZLF group showed significantly improved cardiac function compared with CME alone (P<0.05). Compared with the control group, the myocardial apoptosis rate and the levels of activated caspase-9 and -3 increased significantly in the CME group (P<0.05). Again, these effects were ameliorated by metoprolol and ZLF (P<0.05).


CONCLUSIONS
The present study demonstrates that metoprolol and ZLF can protect the rat myocardium during CME by inhibiting apoptosis and improving cardiac function, likely by inhibiting apoptosis/ mitochondrial apoptotic pathway. These results suggest that antiapoptotic therapies may be useful in treating CME.
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Qiang
Q
Su
Lang
L
Li
Yang-Chun
YC
Liu
You
Y
Zhou
Yong-Guang
YG
Lu
Wei-Ming
WM
Wen
Apoptosis; Caspase-3; Caspase-9; Coronary microembolization; Metoprolol