OMEGA-3 LIPID INFUSION IN A HEART ALLOTRANSPLANT MODEL - SHIFT IN FATTY-ACID AND LIPID MEDIATOR PROFILES AND PROLONGATION OF TRANSPLANT SURVIVAL

Background omega-3 Fatty acids may have a major impact on immune respo nses involved in heart transplant rejection. We compared the effects o f posttransplant intravenous supplementation with omega-3-rich versus omega-6-rich lipid emulsions on graft survival, plasma fatty acid prof iles, and levels of arachidonic acid versus eicosapentaenoic acid-deri ved lipid mediators. Methods and Results Inbred PVG and Wistar-Kyoto r ats were used as donors and recipients, respectively, in a model of he terotopic heart transplantation. Animals received 9 g/kg body wt per d ay of either fish oil-derived (n=8) or soybean oil-derived fat (n=7) i n the form of a continuously infused lipid emulsion; controls were sha m-infused with saline (n=8). Graft rejection was assessed by loss of a ctivity of the transplant. The fish oil-derived preparation but not th at originating from soybean oil caused an increase in total and free p lasma fatty acids. Substantial quantities of eicosapentaenoic acid and docosahexaenoic acid appeared in the free fatty acid fraction, surpas sing those of arachidonic acid. Ex vivo stimulation of neutrophils wit h the Ca2+ ionophore A23187 demonstrated an increase in 5-series leuko triene (LT) generation in animals undergoing omega-3 lipid infusion (L TB(5), omega-oxidation products of LTB(5), LTA(5) secretion), with 5-s eries/4-series LT ratios ranging between 0.08 and 0.36. Ratios of TX B -3/B-2 liberated from ex vivo stimulated platelets even approached 1:1 in omega-3 supple mented rats. Graft survival was 7.6+/-0.3 (mean+/-S EM) days in saline-infused, 10.4+/-0.7 in omega-6 lipid-infused, acid 12.9+/-0.4 in omega-3 lipid-infused animals. Conclusions Posttransplan t intravenous alimentation with fish oil-derived lipid emulsions prolo ngs heart transplant survival in excess to omega-6 lipids. Profound ch anges in fatty acid profiles and lipid mediator generation may underli e this finding.