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We examined an 8-hour cardiopulmonary preservation technique and the role of free radical-induced injury during cardiopulmonary preservation and transplantation. Hence, donor dogs were placed on cardiopulmonary bypass, rapidly cooled to 15 degrees C, and heterotopic heart-unilateral left lung transplantations were performed. In group 1 (n = 5), hearts and lungs were transplanted immediately after core-cooling and cardioplegic arrest. In groups 2 to 5 (n = 5 in each group), heart-lung blocks were excised and stored at 4 degrees C for 8 hours before transplantation. During preservation hearts were perfused (20 mm Hg) with oxygenated extracellular solution (pH 7.4, 410 m0sm/L) and the lungs immersed in the same solution. In groups 3 through 5 recombinant human superoxide distumase (r,h-SOD, total 40 mg/kg) was administered during either donor cooling, donor preservation, or just before and during reperfusion, respectively. Load independent analysis of myocardial function was assessed by determining the ratio of the end-systolic pressure to end-systolic dimension. Pulmonary preservation was evaluated by determination of extravascular lung water of the implanted left lung, arterial oxygenation on 40% inspired oxygen, and pulmonary vascular resistance. Although arterial oxygenation was similar in each group, pulmonary vascular resistance was increased in groups 2 through 4 after implantation. Furthermore, in groups 2 and 4 impaired myocardial function and increased extravascular lung water were observed. Administration of r,h-SOD, however, just before and during reperfusion significantly enhanced cardiopulmonary preservation. These results indicate that free radical-induced injury is primarily the result of reperfusion. Thus the best time for administration of r,h-SOD is before and during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)