LIPID-MEDIATED MODIFICATION OF RAT-HEART ALLOGRAFT SURVIVAL

The effect on allograft survival of intravenous fat emulsions that differed in the ratio of functionally important n-3 and n-6 fatty acids was studied in a heterotopic cardiac transplant model in rats. Twenty percent fat emulsions were administered by continuous infusion at a dosage of 9 g fat/kg body weight per day, starting immediately after transplantation and continuing until complete rejection. The n-6 and n-3 fatty acids represent 75 %, 43 %, 60 %, and 59 % of all fatty acids in safflower oil, fish oil, soybean oil, and a 1:1 mixture of safflower and fish oil, respectively. The n-6 fatty acids predominate in safflower oil (370/1) and soybean oil (6.5/1), while the n-3 fatty acids dominate in the fish oil (7.6/1). The 1:1 mixture of safflower and fish oil has the balanced composition (n-6/n-3 = 2.1/1) recommended by Kinsella and served as oil-treated controls. Continuous infusion of safflower oil, fish oil, and soybean oil prolonged graft survival time to 13.3, 12.3, and 10.4 days, respectively, compared to 6.8 days in the oil-treated controls (P < 0.01 for all comparisons). Another control group infused with saline rejected the allografts after 7.8 days (P = NS compared to oil-treated controls; P < 0.01 for all other comparisons). The data suggest that intravenous administration of polyunsaturated fat emulsions results in an immunosuppressive effect that seems to be dependent on the n-3/n-6 fatty acid ratio of the fat emulsion. The n-6 fatty acids turned out to be just as immunosuppressive as the n-3 fatty acids if each fatty acid family was applied as the main polyunsaturated fatty acid source. Soybean oil with a n-3/n-6 fatty acid ratio, coming closer to the ratio of the oil-treated controls, was significantly less immunosuppressive than safflower oil.