Beta blocker metoprolol protects against contractile dysfunction in rats after coronary microembolization by regulating expression of myocardial inflammatory cytokines.

摘要

AIMS: To examine the effects of metoprolol on expression of myocardial inflammatory cytokines and myocardial function in rats following coronary microembolization (CME). MAIN METHODS: Male rats were randomly assigned to receive either sham-operation (control group), CME plus saline (CME group), or CME plus metoprolol (metoprolol group). CME was induced by injecting 3000 polyethylene microspheres (42 mum) into the left ventricle during a 10-second occlusion of the ascending aorta. Metoprolol (2.5mg/kg) or saline was administered as three intravenous bolus injections after CME. At 3h, 6h, 12h, 24h and 4 weeks after CME, myocardial function was measured with echocardiography; and the mRNA and protein levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10) and interleukin 1-beta (IL-1beta) were determined. KEY FINDINGS: Induced CME led to markedly higher mRNA and protein levels of TNF-alpha, IL-1beta and IL-10 at 3, 6, 12, and 24h, as well as reduced left ventricular function, compared to the control group. Metoprolol administration reduced TNF-alpha and IL-1beta levels, but increased IL-10 levels at 3, 6, 12, and 24h compared to the CME group. Moreover, metoprolol treatment resulted in significantly improved left ventricular function at 12h, 24h and 4 weeks, but afforded no cardiac protection at 3h and 12h, compared to the CME group. SIGNIFICANCE: Higher levels of TNF-alpha and IL-1beta in rats following CME are associated with the development of myocardial contractile dysfunction. Metoprolol-conferred protection against progressive contractile dysfunction following CME may be mediated by its anti-inflammation potential.