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An increase in oxygen tension is an important factor in decreasing pulmonary vascular resistance (PVR) at birth. Birth asphyxia results in acidosis and increased PVR. We determined the effect of resuscitation with 21 vs. 100% O2 on pulmonary hemodynamics, pulmonary arterial (PA) reactivity, and oxidant stress in a lamb model of in utero asphyxia. Term fetal lambs were acutely asphyxiated by intrauterine umbilical cord occlusion for 10 min resulting in acidosis (pH 6.96 ± 0.05 and Pco2 103 ± 5 Torr), bradycardia, systemic hypotension, and increased PVR. Lambs were treated with 30 min of resuscitation with 21% or 100% O2 ( n = 6 each). PaO2 was significantly elevated with 100% O2 resuscitation compared with 21% O2 (430 ± 38 vs. 64 ± 8 Torr), but changes in pH and PaCO2 were similar. The 100% O2 induced greater increase in pulmonary blood flow and decrease in PVR at 1 min of life, but subsequent values were similar to 21% O2 group between 2 and 30 min of life. Oxygen uptake from the lung and systemic oxygen extraction was similar between the two groups. Pulmonary arteries showed increased staining for superoxide anions and increased contractility to norepinephrine following resuscitation with 100% O2. The increased PA contractility induced by 100% O2 was reversed by scavenging superoxide anions with superoxide dismutase and catalase. We conclude that resuscitation of asphyxiated lambs with 100% O2 increases PaO2 but does not improve lung oxygen uptake, decrease PVR at 30 min, or increase systemic oxygen extraction ratios. Furthermore, 100% O2 also induces oxidative stress and increases PA contractility. These findings support the new neonatal resuscitation guidelines recommending 21% O2 for initial resuscitation of asphyxiated neonates.

Recent studies suggest that a bronchial-derived relaxing factor (BrDRF) decreases the contractility of newborn, but not fetal, rat pulmonary arteries (PAs) by a nitric oxide (NO)-mediated mechanism. We studied the effect of an adjacent bronchus on PA contractility to norepinephrine (NE) in late-gestation fetal ( n = 7), neonatal (1 day old, n = 9), ventilated neonatal (24-h ventilation from birth with 100% oxygen, n = 9), and adult sheep ( n = 6) in the presence and absence of the NO synthase inhibitor Nω-nitro-l-arginine (l-NNA). The sheep were anesthetized and killed, and fifth-generation PA rings with and without an attached adjacent bronchus (PA+Br) were contracted in standard tissue baths with NE (10−8–10−6 M). NE contractions were expressed as fraction of KCl (118 mM) contraction and as grams of contraction force. NE contractions were significantly diminished by the presence of an attached bronchus in the neonatal and ventilated neonatal and adult, but not fetal, lambs. Hyperoxic ventilation markedly increased NE contractions in PA and PA+Br. l-NNA significantly enhanced NE contractions in PA+Br in postnatal but not in fetal lambs. Pretreatment with l-NNA abolished the difference between NE contractions in PA and PA+Br in neonatal but not in hyperoxic ventilated neonatal lambs. We conclude that there is a BrDRF that is developmentally regulated and has vascular activity postnatally but not during fetal life. The effect of BrDRF is predominantly mediated by NO in air-breathing neonatal lambs but may involve a second non-NO mediator following hyperoxic ventilation. We speculate that BrDRF may have an important role in postnatal changes in pulmonary arterial reactivity.