Effects of pretreatment with metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization in rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of metoprolol on cardiomyocyte apoptosis and caspase-8 activation after coronary microembolization(CME) in rats.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>Metoprolol pretreatment reduced post-CME myocardial apoptosis possibly through downregulating death receptor-mediated apoptotic pathway.</p>

Effect of metoprolol on myocardial apoptosis after coronary microembolization in rats / 世界急诊医学杂志（英文）

@#BACKGROUND: Coronary microembolization (CME) is a serious complication following percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. The use of metoprolol before PCI can significantly protect ischemic myocardium from myocardial damage, but the function of metoprolol in the treatment of CME is not entirely clear. This study was to explore the effect and significance of metoprolol on myocardial apoptosis and caspase-3 activation after CME in rats. METHODS: Thirty rats were randomly divided into three groups including sham-operation (control group), CME plus saline (CME group), CME plus metoprolol (metoprolol group), 10 rats for each group. The CME group was induced by injecting 3000 polyethylene microspheres (42 μm) into the left ventricle during a 10-second occlusion of the ascending aorta; the control group was injected with physiological saline instead of microembolization ball; the metoprolol or saline group was given three intravenous bolus injections before CME. Echocardiography, TUNEL staining, and Western blotting were used to evaluate cardiac function, proportion of apoptotic cells and activation of caspase-3 respectively at 6 hours after operation. RESULTS: Echocardiographic parameters displayed that the metoprolol group improved cardiac function significantly compared with the CME group (P<0.05). The myocardial apoptotic rate of the CME group as wel as the contents of activated caspase-3 increased significantly (P<0.05), both of which were ameliorated significantly by metoprolol treatment (P<0.05). CONCLUSIONS: This study demonstrates that metoprolol can protect the myocardium during CME in rats by inhibiting apoptosis and improving cardiac function. These results suggest that the inhibition of apoptosis can be a potential therapeutic strategy for the treatment of CME.

Coronary microembolization induced myocardial contractile dysfunction and tumor necrosis factor-α mRNA expression partly inhibited by SB203580 through a p38 mitogen-activated protein kinase pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The microemboli produced during spontaneous plaque rupture and ulceration and during coronary intervention will reduce coronary reserve and cause cardiac dysfunction. It is though that inflammation caused by the microinfarction induced by the microembolization may play an essential role. It is known that the activation of p38 mitogen-activated protein kinases (MAPK) in both infected and non-infected inflammation in myocardium may cause a contractile dysfunction. But the relation between the activation of p38 MAPK and microembolization is still unknown.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into three groups: Sham group, coronary microembolization (CME) group and SB203580 group (n = 10 per group). CME rats were produced by injection of 42 µm microspheres into the left ventricle with occlusion of the ascending aorta. SB203580, a p38 MAPK inhibitor, was injected into the femoral vein after the injection of microspheres to make the SB203580 group. Left ventricular ejection fraction (LVEF) was determined by echocardiography. The protein concentration of P38 MAPK in the myocardium was assessed by Western blotting. The relative expression of mRNA for tumor necrosis factor (TNF)-α was assessed by the technique of semi-quantitative polymerase chain reaction amplification.</p><p><b>RESULTS</b>LVEF was depressed at three hours up to 12 hours in the CME group. Increased p38 MAPK activity and TNF-α mRNA expression were observed in the CME group. The administration of SB203580 partly inhibited p38 MAPK activity, but did not fully depress the TNF-α expression, and partly preserved cardiac contractile function.</p><p><b>CONCLUSIONS</b>p38 MAPK is significantly activated by CME and the inhibition of p38 MAPK can partly depress the TNF-α expression and preserve cardiac contractile function.</p>