Differential effects of inhaled nitric oxide on normoxic and hypoxic isolated in situ neonatal pig lungs perfused by extracorporeal membrane oxygenation

Marilyn W. Butler, Eric L. Lazar, Arthur J. Smerling, Charles J.H. Stolar

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Inhaled nitric oxide (NO) is effective as a selective pulmonary vasodilator, but its effects on uninjured lungs subjected to normoxia and hypoxia have not been fully studied. The authors sought the response of pulmonary vascular resistance (PVR) to inhaled NO in piglet lungs devoid of ischemic injury in a model of reversible pulmonary hypertension. If the changes were dose-responsive, the authors asked whether the PVR changes were related to normoxia or hypoxia, and hypothesized that the change would be more pronounced for hypoxia than normoxia. In situ isolated piglet lungs were prepared by occlusive tracheostomy and ligation of the ductus arteriosus and aorta. Cannulae positioned in the left atrium and pulmonary artery were connected to a standard extracorporeal membrane oxygenation (ECMO) circuit, and flow was increased to approximate cardiac output. After stabilization, piglets (aged 5 to 14 days, weighing 3.2 to 6.4 kg) were divided into two groups of four each: normoxic (Fio2 0.30, normal PVR) and hypoxic (Fio2 0.07, increased PVR). NO was administered at 10 to 80 parts per million (ppm) in increments of 10 ppm, for 5 minutes at each concentration, with a return to baseline before each new dose. Flow, pulmonary arterial (PA) and left atrial (LA) pressures were continuously monitored, from which PVR was calculated (PVR = [PPA - PLA]/flow) and expressed as logΔPVR. Data were analyzed statistically by repeated measures of analysis of variance, comparing logΔPVR to baseline at each dose of NO, and comparing logΔPVR for normoxic and hypoxic lungs at each dose of NO. The authors found: (1) NO significantly decreased PVR at all doses in both normoxic and hypoxic piglet lungs (P < .05). (2) Effects of NO were dose-dependent (P < .05). (3) Normoxic piglet lungs showed a steady decline in PVR throughout the entire dose range. (4) Hypoxic piglet lungs had a rapid decrease in PVR, with maximum effect at 30 to 40 ppm. In conclusion: (1) This model allows reversible pulmonary hypertension in normal lungs, with physiological responses to hypoxia and NO. (2) NO reduces PVR even in normoxia; however, intrinsic endogenous NO release may account for the more attenuated response to inhaled NO. (3) The more exaggerated response to NO in hypoxia may result from increased sensitivity in the face of decreased endogenous release of NO.

Original languageEnglish (US)
Pages (from-to)275-279
Number of pages5
JournalJournal of pediatric surgery
Volume29
Issue number2
DOIs
StatePublished - Feb 1994

Keywords

  • Pulmonary hypertension
  • inhaled nitric oxide, extracorporeal membrane oxygenation (ECMO)

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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