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The end-expiratory lung-volume level of premature newborn infants is maintained above passive resting volume during active breathing, through the combination of reduced time constant and high respiratory rate. To determine whether nasal continuous positive airway pressure (NCPAP) alters this characteristic dynamic breathing pattern, we studied the effects of various NCPAP levels on the dynamic elevation of end-expiratory lung volume level (DeltaEELV) in spontaneously breathing premature newborn infants, using respiratory inductive plethysmography (RIP). Eleven premature newborn infants with moderate respiratory failure were included. NCPAP levels were set in a random order to 0, 2, 4, and 6 cm H2O. Tidal volume (Vt), rib-cage contribution to Vt (%RC), phase angle between abdominal and thoracic motions (theta), respiratory rate (RR), and inspiratory and expiratory times (Ti and Te) were continuously recorded by RIP. The slope of the linear part of the expiratory flow-volume relation was extrapolated up to zero flow level to evaluate the dynamic elevation of the functional residual capacity (FRC) (DeltaEELV). The time-constant of the respiratory system (tauRS) was calculated as the slope of the linear part of the expiratory flow-volume loop. At NCPAP = 6 cm H2O, DeltaEELV reached 0.6 +/- 0.2 times the Vt at NCPAP = 0 cm H2O. An increase in NCPAP level resulted in a significant decrease in DeltaEELV (P < 0.01). A decrease in DeltaEELV during NCPAP was associated with a significant increase in Te from 0.62 +/- 0.13 sec at NCPAP = 0 cm H2O to 0.80 +/- 0.07 sec at NCPAP = 6 cm H2O (P < 0.05), and a decrease in tauRS from 0.4 +/- 0.1 sec at NCPAP = 0 cm H2O to 0.24 +/- 0.04 sec at NCPAP = 6 cm H2O (P < 0.01). These results indicate that the characteristic spontaneous breathing pattern causing a dynamic elevation of FRC is abolished by NCPAP. We speculate that the dynamic volume-preserving mechanisms resulting from expiratory flow braking are no longer required during NCPAP, as the constant pressure may passively elevate FRC.

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Recent in vitro studies reported that nitric oxide release and pulmonary vasorelaxation can be mediated by endothelial ␣ 2 -adrenoceptor activation. As norepinephrine (␣ 1 -,␣ 2 -, and ␤ 1 -adrenoceptor agonist) was found to induce pulmonary vasodilation in the ovine fetus, we hypothesized that ␣ 2 -adrenoceptors may modulate basal pulmonary vascular tone and mediate the vascular effect of norepinephrine during fetal life. To determine the role of ␣ 2 -adrenoceptors and the mechanisms of norepinephrine-mediated vasodilation in the fetal pulmonary circulation, we tested, in chronically prepared late-gestation fetal lambs, the hemodynamic response to 1) yohimbine (␣ 2 antagonist); 2) UK 14,304 (␣ 2 agonist) with and without L-nitro-arginine (nitric oxide synthase inhibitor); and 3) norepinephrine infusion with and without yohimbine. We found that yohimbine increased mean pulmonary artery pressure by 15% (p Ͻ 0.05), decreased pulmonary flow by 22% (p Ͻ 0.01), and increased pulmonary vascular resistance by 51% (p Ͻ 0.01). UK 14,304 increased pulmonary flow by 145% (p Ͻ 0.01) and decreased pulmonary vascular resistance by 58% (p Ͻ 0.01). L-Nitro-arginine abolished the UK 14,304-mediated pulmonary vasodilation. Norepinephrine (0.5 g·kg Ϫ1 ·min Ϫ1 ) increased both pulmonary flow by 61% (p Ͻ 0.01) and pulmonary arterial pressure by 13% (p Ͻ 0.01) and decreased pulmonary vascular resistance by 33% (p Ͻ 0.01). Yohimbine abolished the norepinephrine-induced pulmonary vasodilation. This study suggests that 1) a basal ␣ 2 -adrenoceptor activation-induced pulmonary vasodilation exists during fetal life; 2) the pulmonary vascular effects of ␣ 2 -adrenoceptor activation are related at least in part to nitric oxide production; and 3) the norepinephrine-mediated pulmonary vasodilation involves ␣ 2 -adrenoceptor activation. As a surge of norepinephrine exists at birth, we speculate that norepinephrine and endothelial ␣ 2 -adrenoceptor activation may play a significant role in pulmonary vasodilation at birth. High resistance and low blood flow characterize the fetal pulmonary circulation. PVR decreases dramatically during the normal transition from the fetal to neonatal circulation at birth. Three main factors contribute to the increase of Q p during this transition: ventilation of the lung (1), increased O 2 (2), and hemodynamic forces, such as increased shear stress (3). Vasoactive mediators released from the endothelium, such as NO, play a major role in the regulation of acute changes in vascular tone in the perinatal lung, and in many cases, modulate the pulmonary vascular response to these birth-related stimuli (4). Inhibition of NO synthesis can attenuate the postnatal adaptation of the pulmonary circulation (5). The vasodilator action of several substances, such as acetylcholine, bradykinin, or ADP, and shear stress are dependent, at least in part, on NO release (6). More recently, in vitro studies reported that NO release and pulmonary vasorelaxation can also be mediated by endothelial ␣ 2 -adrenoceptor activation (7-9). Ho...

Objective: Adaptation to extra-uterine life requires dramatic increase in pulmonary blood flow. Mechanisms that induce pulmonary vasodilatation at birth are incompletely understood but include alveolar ventilation, increase in PaO₂, and production of vasoactive mediators. We hypothesized that antenatal glucocorticoids (GC) increase pulmonary vasodilatation to birth-related stimuli. Study Design: To test this hypothesis, we studied the pulmonary hemodynamic response at birth to mechanical ventilation with low (<10%) and then with high (100%) FiO₂ in chronically prepared late-gestation fetal lambs treated or not by antenatal maternal steroids. Results: Basal mean aortic and pulmonary artery pressure (PAP), left pulmonary blood flow, pulmonary vascular resistance (PVR), and blood gas were similar between control and dexamethasone-treated animals (GC group). During mechanical ventilation with low FiO₂, mean PVR decreased by 40% in the control group (from 0.44 ± 0.01 to 0.25 ± 0.01 mm Hg/ml/min) and by 60% in the GC group (from 0.44 ± 0.02 to 0.19 ± 0.02 mm Hg/ml/min) (p < 0.01). When subsequently ventilated with 100% O₂, there was no difference in PVR decrease between groups (0.15 ± 0.02 mm Hg/ml/min in the GC group vs. 0.14 ± 0.01 mm Hg/ml/min in the control group). Conclusion: Antenatal GC enhance pulmonary vasodilatation induced by alveolar ventilation at birth but do not alter the pulmonary vascular response to O₂. We speculate that antenatal steroids exposure improve adaptation at birth through acceleration of both parenchymal and vascular lung maturation.

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