EFFECT OF INTRAVENOUS LIPID EMULSIONS ENRICHED WITH GAMMA-LINOLENIC ACID ON PLASMA N-6 FATTY-ACIDS AND PROSTAGLANDIN BIOSYNTHESIS AFTER BURN AND ENDOTOXIN INJURY IN RATS

Objective: To study the effect of intravenous lipid emulsions enriched with gamma-linolenic acid on plasma fatty acids and series-2 prostagl andins to determine if the slow conversion of linoleic acid by DELTA-6 -desaturase to gamma-linolenic acid could be bypassed to provide subst rate for the formation of dihomo-gamma-linolenic acid, the immediate p recursor for series-1 prostaglandins, in control and injured rats. Dih omo-gamma-linolenic acid can also compete with arachidonic acid for ox idative metabolism by cyclooxygenase to modulate series-2 prostaglandi n biosynthesis. Design: Prospective, randomized, controlled, double-bl ind study. Setting: Research laboratory at a university medical center . Subjects: Thirty-three control and thirty-one injured male Sprague-D awley rats were randomized into one of four parenteral dietary treatme nt groups. Interventions: Rats were injured by the combined actions of a 30% body surface area full-thickness skin burn and a nonlethal inje ction of endotoxin (1 mg/kg ip). The rats were parenterally fed 200 kc al/kg/day, 1.5 g nitrogen/kg/day, and 30% of nonprotein calories as li pid (20% soybean lipid emulsion enriched with 2.7%, 4.4%, or 6.1% gamm a-linolenic acid derived from borage oil) for 3 days. Control rats wer e treated similarly but were not injured. A 20% soybean/safflower oil lipid emulsion was used as the control diet (0% gamma-linolenic acid). Plasma was analyzed on day 3 to determine the concentrations of total fatty acids, thromboxane B2, 6-keto-prostaglandin F1alpha, and bicycl o-prostaglandin E. Measurements and Main Results: Parenteral nutrition with 2.7%, 4.4%, and 6.1% gamma-linolenic acid increased the plasma p ercentages (mol%) of gamma-linolenic acid and dihomo-gamma-linolenic a cid in a dose-dependent fashion in control and injured rats. Supplemen tation with gamma-linolenic acid did not increase the plasma percentag e of arachidonic acid as compared with the 0% gamma-linolenic acid lip id emulsion in control and injured rats. The ratio of dihomo-gamma-lin olenic acid to arachidonic acid was significantly increased in respons e to 4.4% and 6.1% gamma-linolenic acid in both the control and injure d groups. The plasma ratio of thromboxane B2 to 6-keto-prostaglandin F 1alpha was substantially reduced with gamma-linolenic acid compared wi th 0% gamma-linolenic acid in injured rats. Bicyclo-prostaglandin E co ncentration was significantly higher with 2.7% gamma-linolenic acid in injured rats. Injured rats were protein catabolic, as evidenced by a net negative nitrogen balance and loss of body mass compared with cont rols, but neither group showed overt signs of intolerance to the diets . Conclusions: Supplementation of parenteral nutrition with gamma-lino lenic acid had the following effects: a) increased plasma gamma-linole nic acid, dihomo-gamma-linolenic acid, and bicyclo-prostaglandin E; b) increased the plasma ratio of dihomo-gamma-linolenic acid to arachido nic acid; and c) favorably reduced the ratio of thromboxane B2 to 6-ke to-prostaglandin F1alpha in injured rats. These results reflect the po tential capacity of gamma-linolenic acid-enriched lipid emulsions to h ave the following actions: a) to increase dihomo-gamma-linolenic acid, which is the fatty acid precursor of the antiaggregatory, anti-inflam matory eicosanoid, prostaglandin E1; and b) to modulate arachidonic ac id-derived series-2 prostaglandins after injury.