LABORATORY INVESTIGATION

ABSTRACT It has been established that glucocorticoids and several nonsteroidal antiinflammatory drugs, when administered early after coronary occlusion, interfere with myocardial scar formation. To determine whether this action is associated with expansion of myocardial infarct during the first week of coronary occlusion and whether expansion affects ventricular function, the effects of indomethacin on the left ventricle in the early phase of infarction were studied. In a blinded randomized study, experimental myocardial infarction was produced in 17 open-chest dogs by ligation of the proximal left anterior descending coronary artery; the treated group (n 8) received 10 mg/kg iv indomethacin at 15 min and 3 hr after occlusion, and the control group (n 9) received saline. After 7 days, regional function expressed as percent change of area (%zXA) of the left ventricular cavity was calculated from short-axis two-dimensional echocardiograms at the level of the infarct, the animals were killed, and their hearts were examined. The ratio of infarct thickness to noninfarcted wall thickness was 1.20 + 0.08 (mean SEM) in the control group, and the ratio was lower in the indomethacin group, 0.96 + 0.04 (p <.025). An expansion index of myocardial infarction was calculated as previously described and was 1.02 0.04 in the control group vs 1.29 + 0.06 in the indomethacin group (p <.005). In eight dogs (six control and two treated) without expansion (expansion index less than 1.09), regional function expressed as %AA was 46.8 + 2.6 % (SEM), and in nine dogs (six treated and three control) with expansion, %AA was significantly lower, 28.7 ± 4.0 % (p <.005). In conclusion, indomethacin prevents the normal thickening of an infarct early in the healing phase; this interference with healing is associated with infarct expansion that in turn is associated with impaired regional function