Exposure to hyperoxia in newborn mice increases long-term airway reactivity with persistent lung inflammation associated with a marked increase in lymphocytes, suggesting long-term consequences in adults. Pediatr Pulmonol. 2016;51:1131-1141. © 2016 Wiley Periodicals, Inc.

ObjectivesNeonatal resuscitation guidelines recommend 0.5–1 mL saline flush following 0.01–0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest.DesignForty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored.ResultsTen lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush.Conclusions0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted.

C-type natriuretic peptide (CNP) is a recently described endothelium-derived relaxing factor. CNP relaxes vascular smooth muscle and inhibits smooth muscle proliferation by binding to natriuretic peptide receptor (NPR) type B (NPR-B) and producing cGMP. Lung parenchyma and fifth-generation pulmonary arteries (PA) and veins (PV) were isolated from late-gestation fetal lambs. All three types of NPR mRNA were detected in PA and PV by RT-PCR. CNP and NPR-B immunostaining was positive in pulmonary vascular endothelium and medial smooth muscle. CNP concentration-response curves of PA and PV were compared with those of atrial natriuretic peptide (ANP) by use of standard tissue bath techniques. CNP relaxed PV significantly better than PA. ANP relaxed PA and PV equally, but ANP relaxed PA significantly better than CNP. Pretreating PA and PV with natriuretic peptide receptor blocker (HS-142-1) or cGMP-dependent protein kinase inhibitor Rp-beta-phenyl-1- N2-etheno-8-bromoguanosine 3',5'-cyclic monophosphorothionate significantly inhibited the CNP relaxation response, indicating that the response was mediated through the NPR-cGMP pathway. We conclude that CNP is important in mediating pulmonary venous tone in the fetus.

BackgroundCurrent neonatal resuscitation guidelines recommend tracheal suctioning of non-vigorous neonates born through meconium stained amniotic fluid.MethodsWe evaluated the effect of tracheal suctioning at birth in 29 lambs with asphyxia induced by cord occlusion and meconium aspiration during gasping.ResultsTracheal suctioning at birth (n=15) decreased amount of meconium in distal airways (53±29 particles/mm2 lung area) compared to no-suction (499±109 particles/mm2, n=14, p<0.001). Three lambs in the suction group had cardiac arrest during suctioning requiring chest compressions and epinephrine. Onset of ventilation was delayed in the suction group (146±11 vs. 47±3 sec in no-suction group, p=0.005). There was no difference in pulmonary blood flow, carotid blood flow, pulmonary or systemic blood pressure between the two groups. Left atrial pressure was significantly higher in the suction group. Tracheal suctioning resulted in higher PaO2/FiO2 levels (122±21 vs. 78±10 mmHg) and ventilator efficiency index (0.3±0.05 vs.0.16±0.03). Two lambs in the no-suction group required inhaled NO. Lung 3-nitrotyrosine levels were higher in the suction group (0.65±0.03 ng/μg protein) compared to the no-suction group (0.47 ± 0.06).ConclusionTracheal suctioning improves oxygenation and ventilation. Suctioning does not improve pulmonary/systemic hemodynamics or oxidative stress in an ovine model of acute meconium aspiration with asphyxia.

BACKGROUND Cases of necrotizing enterocolitis occurring within 48 h of packed red blood cell (PRBC) transfusions are increasingly being described in observational studies. Transfusion-associated gut injury is speculated to result from an abnormal mesenteric vascular response to transfusion. However, the mechanism of disruption of the balance between mesenteric vasoconstriction and relaxation following transfusion is not known. METHODS Preterm lambs (n = 16, 134 d gestation; term: 145–147 d) were delivered and ventilated for 24 h. All the lambs received orogastric feeds with colostrum. In addition, 10 of these lambs received PRBC transfusions. Vasoreactivity was evaluated in isolated mesenteric arterial rings using norepinephrine and endothelin-1 as vasoconstrictors. Endothelium-dependent (A23187, a calcium ionophore) and endothelium-independent (SNAP) nitric oxide (NO) donors were used as vasorelaxants. Mesenteric arterial endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC), and phosphodiesterase 5 (PDE5) mRNA analyses and protein assays were performed. RESULTS Transfusion with PRBC significantly increased mesenteric vasoconstriction to norepinephrine and endothelin-1 and impaired relaxation to A23187 and SNAP. Mesenteric arterial eNOS protein decreased following PRBC transfusion. No significant changes were noted in sGC and PDE5 mRNA or protein assays. CONCLUSION PRBC transfusion in enterally fed preterm lambs promotes mesenteric vasoconstriction and impairs vasorelaxation by reducing mesenteric arterial eNOS.