ω-3 Lipid Infusion in a Heart Allotransplant Model

Abstract

Background ω-3 Fatty acids may have a major impact on immune responses involved in heart transplant rejection. We compared the effects of posttransplant intravenous supplementation with ω-3–rich versus ω-6–rich lipid emulsions on graft survival, plasma fatty acid profiles, and levels of arachidonic acid versus eicosapentaenoic acid–derived lipid mediators. Methods and Results Inbred PVG and Wistar-Kyoto rats were used as donors and recipients, respectively, in a model of heterotopic heart transplantation. Animals received 9 g/kg body wt per day of either fish oil–derived (n=8) or soybean oil–derived fat (n=7) in the form of a continuously infused lipid emulsion; controls were sham-infused with saline (n=8). Graft rejection was assessed by loss of activity of the transplant. The fish oil–derived preparation but not that originating from soybean oil caused an increase in total and free plasma fatty acids. Substantial quantities of eicosapentaenoic acid and docosahexaenoic acid appeared in the free fatty acid fraction, surpassing those of arachidonic acid. Ex vivo stimulation of neutrophils with the Ca 2+ ionophore A23187 demonstrated an increase in 5-series leukotriene (LT) generation in animals undergoing ω-3 lipid infusion (LTB 5 , ω-oxidation products of LTB 5 , LTA 5 secretion), with 5-series/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 ω-3 supplemented rats. Graft survival was 7.6±0.3 (mean±SEM) days in saline-infused, 10.4±0.7 in ω-6 lipid–infused, and 12.9±0.4 in ω-3 lipid–infused animals. Conclusions Posttransplant intravenous alimentation with fish oil–derived lipid emulsions prolongs heart transplant survival in excess to ω-6 lipids. Profound changes in fatty acid profiles and lipid mediator generation may underlie this finding.