Effects of n-3 polyunsaturated fatty acids in the fetal pulmonary circulation

Objective: Although evidence exists that n-3 polyunsaturated fatty acids may improve the outcome in patients with severe respiratory failure, little is known regarding their pulmonary circulatory effects. This question is clinically relevant in respiratory failure associated with pulmonary hypertension, in particular in newborn infants with persistent pulmonary hypertension. The objective of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the fetal pulmonary circulation. Design: Randomized, placebo-controlled comparative laboratory investigation. Setting: University research facility. Subjects: Fifty-two chronically prepared lamb fetuses. Interventions: Catheters and ultrasonic flow transducer were placed through a left thoracotomy in the lamb fetus to determine aortic, pulmonary, and left atrial pressures and left pulmonary artery blood flow. Measurements and Main Results: We compared the pulmonary vascular responses to 120 mins of Omegaven (lipid emulsions enriched in n-3 polyunsaturated fatty acids) or Intralipide (lipid emulsions enriched in n-6 polyunsaturated fatty acids) infusion. Then we investigated the effects of Omegaven on the pulmonary circulation after nitric oxide synthase inhibition by L-nitro-arginine, potassium channel blockade by tetraethylammonium, and cytochrome P450 epoxygenase inhibition by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Pulmonary artery and aortic pressures as well as blood gases and plasma lactate concentrations did not change during either fat emulsion infusion. Left pulmonary blood flow increased by 30% and pulmonary vascular resistance decreased by 28% during Omegaven infusion, whereas left pulmonary blood flow and pulmonary vascular resistance did not change during Intralipide infusion. This pulmonary vascular response to Omegaven was not altered by L-nitroarginine. At the opposite, Omegaven induced pulmonary vasodilatation was abolished by tetraethylammonium and markedly attenuated by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Conclusions: Lipid emulsion containing n-3 polyunsaturated fatty acids may induce a potent and sustained vasodilatation in the fetal lung. This pulmonary vasodilator response is mediated through production of vasoactive mediators by cytochrome P450 epoxygenase and through activation of potassium channels. (Crit Care Med 2011; 39: 1431-1438)