EFFECTS OF ENDOTOXIN ON PIGS PREFED OMEGA-3 VS OMEGA-6 FATTY ACID-ENRICHED DIETS

We investigated in a porcine model whether omega-3 fatty acids modify the physiological response to sepsis. For 8 days, 16 male pigs were fed a diet containing 18% fat by weight enriched with either omega-3 or omega-6 fatty acids (FA). A group of six pigs receiving their regular diet served as controls. The omega-3 FA-supplemented pigs had elevated levels of omega-3 FA in their serum-free FA, serum phospholipid (PL), and platelet PL levels compared with either of the other groups. On the ninth day, the unanesthetized pigs were injected with 0.3 mg/kg of endotoxin (Escherichia coli) intravenously. The animals had a significant decrease in their arterial O2 pressure (Pa(O2)) [from 84.4 +/- 6.8 (SD) to 64 +/- 9.4, and from 83.1 +/- 7.2 to 55.9 +/- 6.3 mmHg in the omega-6 FA and regular diet groups, respectively]. The Pa(O2) did not decrease in the omega-3 FA pigs. The omega-3 FA group had significantly lower pulmonary vascular resistance (541 +/- 205 dyn . s . cm-5) 20 min after endotoxin compared with either the omega-6 FA or regular diet groups (797 +/- 233 and 1,102 +/- 552 dyn . s . cm-5, respectively) and more normal blood pressure compared with the other two groups. Plasma thromboxane (Tx) B2 and 6-ketoprostaglandin F1alpha (6-keto-PGF1alpha) levels were lowest in the omega-3 FA diet group and highest in the regular diet group. The fall in Pao, was correlated with changes in plasma levels of TxB2 measured at the same time as the Pa(O2) (r = -0.64, P < 0.02) and with changes in plasma levels of 6-keto-PGF1alpha (r = -0.51, P < 0.05). It is possible with a short-term diet containing high amounts of omega-3 FA to increase plasma and platelet concentrations of omega-3 FA. These diets reduced the rise in plasma eicosanoid levels and maintained arterial oxygenation, arterial blood pressure, and more normal pulmonary vascular resistance in response to intravenous endotoxin.