Isolated working rat hearts were perfused with the perfluorochemical emulsion Fluosol-43 to determine whether it would support prolonged, stable cardiac function. The perfluorochemical emulsion provides a controlled perfusate composition, relatively high oxygen capacity, and a colloid osmotic pressure that is similar to that of plasma. Electrically paced (325 beats/min) hearts were perfused for 6 h at 35 degrees C in a recirculating system. Hemodynamic and mechanical function of seven Krebs-Henseleit-perfused hearts declined significantly more than that of seven Fluosol-43-perfused hearts over the 6-h period. The percent of initial function remaining at 6 h for Krebs-Henseleit-perfused vs. Fluosol-43-perfused hearts was 70.3 +/- 5.0 vs. 95.4 +/- 1.1% (P less than 0.001) for left ventricular peak systolic pressure; 55.6 +/- 7.7 vs. 97.5 +/- 2.4% (P less than 0.001) for dP/dtmax; 27.1 +/- 7.2 vs. 60.6 +/- 5.2% (P less than 0.005) for cardiac output; 11.0 +/- 6.3 vs. 67.2 +/- 3.4% (P less than 0.001) for external work efficiency; and 17.4 +/- 8.4 vs. 67.7 +/- 4.5% (P less than 0.001) for stroke rhythmic than Fluosol-43-perfused hearts during the last 3 h of perfusion. Perfusate lactate concentration was 4.5-fold higher in the Krebs-Henseleit perfusate than in the Fluosol-43 perfusate at 6 h, reflecting greater anaerobic metabolism in the Krebs-Henseleit-perfused hearts. Thus isolated rat hearts perfused with Fluosol-43 have greater maintenance of hemodynamic and mechanical function over a longer time period than hearts perfused with Krebs-Henseleit bicarbonate buffer.