Dose-dependent effects of short-term methylprednisolone on myocardial infarct extent, scar formation, and ventricular function

Abstract

Treatment with methylprednisolone (MP) of patients with acute myocardial infarcts remains a controversial topic; although some studies have shown that MP reduces infarct size, others have shown that it alters the healing process. To determine whether short-term MP limits infarct size and whether it alters the healing process of function, we investigated effects of different doses of MP or infarct size, scar formation, and cardiac function. Experimental infarction was produced in 23 anesthetized open-chest dogs by ligation of the proximal left anterior descending coronary artery. Group 1 dogs (n = 8) received MP 50 mg/kg iv 15 min and 3, 24, and 48 hr after occlusion (high MP); group 2 (n = 7) received MP 30 mg/kg iv 15 min after occlusion (low MP). Group 3 (n = 8) received saline (control). After 6 weeks of coronary occlusion, two-dimensional (2D) echocardiograms were performed, dogs were killed, and their hearts were examined. Regional function, expressed as percent of change in the area of the left ventricular cavity calculated from short-axis 2D echocardiograms, was markedly reduced in the high MP group with the percent of change in the area of 23.3 ± 4.9% compared with 38.4 ± 3.9% in the control group (p < .05) and with 40.5 ± 4.4% in the low MP group (p < .05). A ratio obtained by dividing infarct thickness by noninfarcted wall thickness was lower in the high MP group (0.42 ± 0.04 mean ± SEM) vs both the low MP group (0.95 ± 0.05) and the control group (0.88 ± 0.07; p < .01). Infarct extent was smaller in the low MP group, with the percent of infarcted endocardial circumference of 19.0 ± 1.9% vs the high MP group (30.0 ± 3.5%; p < .05). The percent of infarcted endocardial circumference in the control group was 25.0 ± 1.8% (p = NS). Scars in the treated and control groups were similar histologically and by hydroxyproline content. Therefore, high MP, but not low MP, caused marked scar thinning associated with reduction in regional function, without a change in collagen content.