Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs

Dyuti Sharma,Véronique Houfflin-Debarge,Estelle Aubry,Rémi Besson,Laurent Storme,Philippe Deruelle,Thavarak Ouk,Ali Houeijeh

doi:10.3390/nu9070761

Abstract

Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E− (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E− (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.

Highlights

Many perinatal conditions such as premature rupture of the membrane, sepsis, meconium aspiration syndrome and pulmonary hypoplasia can promote cardiovascular maladaptation to extrauterine life in the newborn, called persistent pulmonary hypertension of the newborn (PPHN).This syndrome results from sustained elevation of pulmonary vascular resistance (PVR), causing severe hypoxemia
During the infusion of docosahexaenoic acid (DHA), no statistical difference was observed in Heart rate (HR) (164 ± 3, baseline mean (T-40 to T0) vs. 160 ± 3, infusion mean (T0 to T160) beats/min; p = 0.89), pulmonary arterial pressure (PAP) (53 ± 0.5, baseline mean (T-40 to T0) vs. 54 ± 0.4, infusion mean (T0 to T160) mmHg; p = 0.54) or PAo
We found that the infusion of effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on basal pulmonary vascular mg of induced a prolonged pulmonary vasodilatatory response, whereas the infusion of mg tone in chronically monitored fetal lambs during the end of gestation

Summary

Introduction

Many perinatal conditions such as premature rupture of the membrane, sepsis, meconium aspiration syndrome and pulmonary hypoplasia can promote cardiovascular maladaptation to extrauterine life in the newborn, called persistent pulmonary hypertension of the newborn (PPHN). This syndrome results from sustained elevation of pulmonary vascular resistance (PVR), causing severe hypoxemia. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). Rings treated with EPA were separated into three groups: E+ (intact endothelium), E− (endothelium stripped) and LNA E+

Objectives

Methods

Results

Discussion

Conclusion