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.(ABSTRACT TRUNCATED AT 250 WORDS)
Grimm
H
H
Karolinska Institute, Department of Transplantation Surgery, Huddinge Hospital, Stockholm, Sweden.
Tibell
A
A
Norrlind
B
B
Larsson-Backström
C
C
Wretlind
A
A
Groth
C G
CG
D000818:Animals; D005217:Fat Emulsions, Intravenous / Q000737:chemistry / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D014184:Transplantation, Homologous
D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated