Pulmonary Hemodynamics in Neonatal Lambs Resuscitated with 21%, 50%, and 100% Oxygen

Abstract

ABSTRACT:The effect of resuscitation with varying levels of O 2 on pulmonary hemodynamics at birth is not well known. We hypothesized that the decrease in pulmonary vascular resistance (PVR) and subsequent response to pulmonary vasoconstrictors and vasodilators will differ following resuscitation with 21%, 50%, or 100%O 2 for 30 min at birth in normal term lambs. Lambs at 141 d gestation were delivered by cesarean section and ventilated with 21% (21% Res; n ϭ 6), 50% (50% Res; n ϭ 6), or 100% O 2 (100% Res; n ϭ 7) for 30 min followed by ventilation with 21% O 2 in all three groups. A greater decrease in PVR was seen with 50% and 100% O 2 ventilation than with 21% O 2 (0.21 Ϯ 0.02, 0.21 Ϯ 0.02, and 0.34 Ϯ 0.05 mm Hg/mL/min/kg, respectively). Subsequent pulmonary vasoconstriction to hypoxia (10% O 2 ) and the thromboxane analog U46619 (0.5 and 1 g/kg/min) was similar in all three groups. After inducing a stable elevation in PVR with U46619, impaired pulmonary vasodilation to inhaled NO (59 Ϯ 4, 65 Ϯ 4, and 74 Ϯ 5% of baseline PVR with 21, 50, and 100%Res, respectively) and acetylcholine infusion (67 Ϯ 8, 75 Ϯ 6, and 87 Ϯ 4% of baseline PVR with 21, 50, and 100%Res, respectively) and rebound pulmonary hypertension following their withdrawal were observed in the 100%Res group. We conclude that, while ventilation with 100% O 2 at birth results in a greater initial decrease in PVR, subsequent pulmonary vasodilation to NO/acetylcholine is impaired. (Pediatr Res 62: 313-318, 2007) F etal pulmonary vascular resistance is high and O 2 plays a crucial role in mediating the pulmonary vascular transition at birth (1). However, the optimal level of O 2 supplementation during resuscitation of a newborn infant remains controversial (2) despite publication of new guidelines (3). During resuscitation of a depressed newborn infant with potentially high PVR, there is concern that room air resuscitation may result in inadequate pulmonary vasodilation. It has been suggested that breathing 100% O 2 dilates constricted pulmonary arteries more efficiently than room air.Previous studies have demonstrated conflicting results regarding the effect of ventilation with different gas mixtures on PVR. Some studies indicate that ventilation with nitrogen, air, and O 2 are similarly effective in reducing fetal PVR in lambs (4,5). Other studies indicate that PVR drops more effectively with 100% O 2 (6) or air (7,8) than with a nitrogen-rich gas. It may be important to find an intermediate level of O 2 that has the advantages of short-term reduction in PVR without the toxicity of 100% O 2 (9,10). Recent studies examined pulmonary hemodynamic responses to 21% or 100% O 2 ventilation, but were conducted on hypoxemic lambs only after 12-72 h of age, after PVR had dropped from high fetal levels immediately after birth (11)(12)(13). Understanding the precise pulmonary hemodynamic response to ventilation with room air, 100% O 2 , and an intermediate level of O 2 exposure (such as 50% O 2 ) in animals at birth is vital for determining the safest protocol ...

Exposure to Supplemental Oxygen and Its Effects on Oxidative Stress and Antioxidant Enzyme Activity in Term Newborn Lambs

“…We have also shown that ventilation with 21% O 2 results in a rapid reduction in pulmonary vascular resistance and does not interfere with subsequent vasodilation to NO and acetylcholine, whereas resuscitation with 100% O 2 impairs vasodilation to these agents (8). Because oxidative stress influences apoptosis and cell growth (9), oxygen exposure may have long-term consequences on growth and development.…”

Part 11: Neonatal Resuscitation

“…14,15 There is evidence in newborn animal models of asphyxia that exposure to high concentrations of oxygen at resuscitation does not confer any clinical advantage and is potentially harmful at the cellular level. 16,17 Two animal models of hypoxia-ischemia and persistent bradycardia found that those resuscitated with room air rather than 100% oxygen developed untoward biochemical changes in the brain (LOE 5 18,19 ).…”

Blunted Hypoxic Pulmonary Vasoconstriction in Experimental Neonatal Chronic Lung Disease

“…O 2 toxicity and/or chronic ventilation, the two main causes contributing to lung injury in premature infants, may impede K v channel expression/ function in the pulmonary vasculature. More recently, the deleterious effect of even brief (30 min) hyperoxia (decreased vasodilation to nitric oxide and acetylcholine) on the pulmonary circulation was reported (39,40). Interestingly, the authors also show that lambs previously exposed for a brief period (30 min) to 100% O 2 did not have enhanced pulmonary vasoconstriction in response to subsequent hypoxic ventilation.…”