12-HOUR CARDIOPULMONARY PRESERVATION USING DONOR CORE COOLING, LEUKOCYTE DEPLETION, AND LIPOSOMAL SUPEROXIDE-DISMUTASE

Because leukocytes and oxygen radical species contribute to ischemic and reperfusion injury during organ preservation, we examined the effect of a long-acting liposomal superoxide dismutase (liposomal SOD) and mechanical filtration of leukocytes on cardiopulmonary graft function after 12 hours of static preservation. Bovine heart-lung blocks were harvested, core cooled to 15-degrees-C, stored in 4-degrees-C donor blood for 12 hours, and then orthotopically transplanted (control group, n = 6). In the leukocyte-depletion group (n = 6), a leukocyte filter was incorporated in the bypass circuits of the donor and recipient. In the SOD group (n = 6), liposomal SOD (5000 U/kg) was administered in the cardioplegic solution, in the prime of the bypass circuits of donor and recipient, and immediately before recipient heart-lung reperfusion. In the combination group (n = 6), both leukocyte depletion (LD) and liposomal SOD were used. Only four of six control animals survived more than 2 hours after weaning from bypass, whereas all LD, SOD, and LD + SOD animals survived to be studied at 6 hours. Pulmonary function was assessed at 6 hours by arterial oxygen tension on 100% inspired oxygen (po2), pulmonary vascular resistance (PVR), and postmortem wet/dry lung weight ratios. Arterial po2 values (mm Hg) were as follows: control, 102 +/- 51; LD, 437 +/- 60*; SOD, 278 +/- 83; and LD + SOD, 504 +/- 54* (*p < 0.05 vs controls). PVR values (dynes . sec . cm5) were as follows: control, 1975 +/- 697; LD, 682 +/- 131*; SOD, 607 +/- 191*; and LD + SOD 367 +/- 87* (*p < 0.05 vs controls). Postmortem wet/dry lung weight ratios were as follows: control, 7.2 +/- 0.3; LD, 6.3 +/- 0.2; SOD, 6.3 +/- 0.3; and LD + SOD, 4.7 +/- 0.3* (*p < 0.05 vs controls). Donor core cooling and leukocyte depletion combined with liposomal SOD provided the best protection. With this technique, extended cardiopulmonary preservation for heart-lung transplantation may be achieved.