Univ. Lille, EA 4489 - Perinatal Environment and Health, Lille, France.
CHU Lille, Department of Pediatric Surgery, Hospital Jeanne de Flandre, Lille, France.
PLoS One. 2018 Jun 27;13(6):e0198778. doi: 10.1371/journal.pone.0198778. eCollection 2018.
Persistent pulmonary hypertension (PPHN) remains a severe complication of the transition to extra-uterine life with significant morbidity and mortality in the newborns. Dehydroepiandrosterone (DHEA) represents a new pharmacological agent with vascular effects, including improvement of PPHN in several animal models. We hypothesized that DHEA could decrease pulmonary vascular resistance (PVR) in the pulmonary circulation of fetal sheep. We studied the effect of intravenous infusion of DHEA in fetal lambs using chronically instrumented sheep at 128 days of gestation. PVR was computed before and after intravenous infusion of increasing doses of DHEA. We assessed pre-treatment by L-nitroarginine, an inhibitor of NO production. Blood gases and doses of DHEA were measured in both sheep and fetus before/after DHEA infusion. Intravenous infusion of DHEA had a vasodilator effect with a significant decrease in PVR (respectively -11%, -14% and -36% after infusion of 6, 12 and 24 mg DHEA, p<0.01) without damaging effects on systemic circulation or on blood gases. The inhibitory effect of pre-treatment with L-nitroarginine resulted in a significant increase in PVR. We demonstrated a potent vasodilator effect of DHEA on fetal pulmonary circulation without deleterious effects. DHEA might represent a new treatment for PPHN.
持续性肺动脉高压（PPHN）仍然是新生儿过渡到宫外生活的严重并发症，具有较高的发病率和死亡率。脱氢表雄酮（DHEA）是一种具有血管作用的新型药物，包括在几种动物模型中改善 PPHN。我们假设 DHEA 可以降低胎儿羊的肺循环中的肺血管阻力（PVR）。我们使用 128 天妊娠的慢性仪器化绵羊研究了静脉内输注 DHEA 对胎儿羊的影响。在静脉内输注递增剂量的 DHEA 之前和之后计算 PVR。我们评估了一氧化氮合酶抑制剂 L-硝基精氨酸预处理的效果。在 DHEA 输注前后测量了羊和胎儿的血气和 DHEA 剂量。静脉内输注 DHEA 具有血管舒张作用，PVR 显著降低（分别在输注 6、12 和 24mg DHEA 后降低 11%、14%和 36%，p<0.01），而对全身循环或血气没有损害作用。L-硝基精氨酸预处理的抑制作用导致 PVR 显著增加。我们证明了 DHEA 对胎儿肺循环具有强大的血管舒张作用，而没有不良影响。DHEA 可能是 PPHN 的一种新治疗方法。
