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

AimsTo examine the effects of metoprolol on expression of myocardial inflammatory cytokines and myocardial function in rats following coronary microembolization (CME).Main methodsMale 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 μm) into the left ventricle during a 10-second occlusion of the ascending aorta. Metoprolol (2.5 mg/kg) or saline was administered as three intravenous bolus injections after CME. At 3 h, 6 h, 12 h, 24 h and 4 weeks after CME, myocardial function was measured with echocardiography; and the mRNA and protein levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and interleukin 1-β (IL-1β) were determined.Key findingsInduced CME led to markedly higher mRNA and protein levels of TNF-α, IL-1β and IL-10 at 3, 6, 12, and 24 h, as well as reduced left ventricular function, compared to the control group. Metoprolol administration reduced TNF-α and IL-1β levels, but increased IL-10 levels at 3, 6, 12, and 24 h compared to the CME group. Moreover, metoprolol treatment resulted in significantly improved left ventricular function at 12 h, 24 h and 4 weeks, but afforded no cardiac protection at 3 h and 12 h, compared to the CME group.SignificanceHigher levels of TNF-α and IL-1β 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.