Glucocorticoid treatment prevents progressive myocardial dysfunction resulting from experimental coronary microembolization

Abstract

Background - The frequency and importance of microembolization in patients with acute coronary syndromes and during coronary interventions have recently been appreciated. Experimental microembolization induces immediate ischemic dysfunction, which recovers within minutes. Subsequently, progressive contractile dysfunction develops over several hours and is not associated with reduced regional myocardial blood flow (perfusion-contraction mismatch) but rather with a local inflammatory reaction. We have now studied the effect of antiinflammatory glucocorticoid treatment on this progressive contractile dysfunction. Methods and Results - Microembolization was induced by injecting microspheres (42-μm diameter) into the left circumflex coronary artery. Anesthetized dogs were followed up for 8 hours and received placebo (n=7) or methylprednisolone 30 mg/kg IV either 30 minutes before (n=7) or 30 minutes after (n=5) microembolization. In addition, chronically instrumented dogs received either placebo (n=4) or methylprednisolone (n=4) 30 minutes after microembolization and were followed up for 1 week. In acute placebo dogs, posterior systolic wall thickening was decreased from 20.0±2.1% (mean±SEM) at baseline to 5.8±0.6% at 8 hours after microembolization. Methylprednisolone prevented the progressive myocardial dysfunction. Increased leukocyte infiltration in the embolized myocardium was prevented only when methylprednisolone was given before microembolization. In chronic placebo dogs, progressive dysfunction recovered from 5.0±0.7% at 4 to 6 hours after microembolization back to baseline (19.1±1.6%) within 5 days. Again, methylprednisolone prevented the progressive myocardial dysfunction. Conclusions - Methylprednisolone, even when given after microembolization, prevents progressive contractile dysfunction.