Differential effects of inhaled nitric oxide on normoxic and hypoxic isolated in situ neonatal pig lungs perfused by extracorporeal membrane oxygenation.
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 log delta PVR. Data were analyzed statistically by repeated measures of analysis of variance, comparing log delta PVR to baseline at each dose of NO, and comparing log delta PVR for normoxic and hypoxic lungs at each dose of NO.(ABSTRACT TRUNCATED AT 250 WORDS)
Butler
M W
MW
Division of Pediatric Surgery, Columbia University, College of Physicians and Surgeons, New York, NY.
Lazar
E L
EL
Smerling
A J
AJ
Stolar
C J
CJ
D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D015199:Extracorporeal Membrane Oxygenation; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000503:physiopathology*; D009569:Nitric Oxide / Q000494:pharmacology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D009569:Nitric Oxide