To assess the effect of Fluosol-DA treatment on infarct morphology, detailed histologic examination was performed in 17 dogs with permanent proximal left anterior descending coronary artery occlusion. Two of the three groups of dogs received an equal blood volume exchange (40 ml/kg i.v.) with either Fluosol-DA (F) or heparinized autologous blood (H) 30 min post occlusion while being ventilated with 100% oxygen. A third group received no therapy (C). Animals were sacrificed 3 days post occlusion and sections were obtained for light and electron microscopy. Histologic studies showed that infarct size was statistically smaller in dogs treated with F 54 +/- 7% versus heparin 64 +/- 10% treatment or no therapy 79 +/- 6%. Fluosol-DA animals demonstrated decreased inflammatory infiltrate, larger viable subepicardial zones and greater endocardial sparing in the area surrounding the central zone of necrosis. By electron microscopy, perfluorochemical particles were found within endothelial and inflammatory cells in subepicardial zones of infarction. In midmyocardial zones, Fluosol-DA particles were present in capillaries, extracellular spaces and necrotic myocytes. In the normal myocardium Fluosol-DA particles were rarely seen within endothelial cells and never within the interstitium or myocytes. Thus, Fluosol-DA reduces infarct size and alters infarct morphology in the 3 day post permanent coronary occlusion model.