title: Hemodynamic effects and metabolic fate of inhaled nitric oxide in hypoxic piglets.
abstract: We describe the hemodynamic effects and metabolic fate of inhaled NO gas in 12 anesthetized piglets. Pulmonary and systemic hemodynamic responses to incremental [NO] (5-80 ppm) were tested during ventilation with high- [0.30 inspired O2 fraction (FIO2)] and low-O2 (0.10 FIO2) mixtures. In six animals, inhalation of 40 ppm NO was maintained over 6 h to test effects of prolonged exposure (0.30 FIO2). In the other six animals, pulmonary hypertension was induced by hypoxic ventilation (0.10 FIO2) and responses to NO were tested. Inhaled low [NO] partially reversed pulmonary hypertension induced by alveolar hypoxia; mean pulmonary arterial pressure decreased from 31.4 +/- 2.3 mmHg during hypoxia to 18.2 +/- 1.2 mmHg during 5 ppm NO. Mean pulmonary arterial pressure at 0.10 FIO2 did not fall further at higher [NO] (10-40 ppm) and never reached control levels. Pulmonary vascular resistance increased with institution of hypoxic ventilation and fell with subsequent administration of NO, ultimately reaching control levels. Inhaled NO did not affect systemic vascular resistance. Plasma levels of NO2- + NO3- and methemoglobin (MetHb) levels increased with increasing [NO]. Over 6 h of NO administration during high-O2 ventilation, MetHb equilibrated at subtoxic levels while NO2- + NO3- increased. Nitrosylhemoglobin, analyzed by electron paramagnetic resonance spectrophotometry was not detected in blood at any time. At the relatively low concentrations (5-80 ppm) that are effective in relieving experimental pulmonary hypertension induced by alveolar hypoxia, inhaled NO gas causes accumulation of NO2- + NO3- in plasma and a small increase in MetHb but no detectable nitrosylhemoglobin.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
authors.forename: T D
authors.initials: TD
authors.lastname: Jacob
authors.forename: D K
authors.initials: DK
authors.lastname: Nakayama
authors.forename: I
authors.initials: I
authors.lastname: Seki
authors.forename: R
authors.initials: R
authors.lastname: Exler
authors.forename: J R
authors.initials: JR
authors.lastname: Lancaster
authors.forename: M A
authors.initials: MA
authors.lastname: Sweetland
authors.forename: S
authors.initials: S
authors.lastname: Yousem
authors.forename: R L
authors.initials: RL
authors.lastname: Simmons
authors.forename: T R
authors.initials: TR
authors.lastname: Billiar
authors.forename: A B
authors.initials: AB
authors.lastname: Peitzman
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006439:Hemodynamics / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D008706:Methemoglobin / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange; D013552:Swine
chemical_list: D006454:Hemoglobins; C008657:nitrosyl hemoglobin; D009569:Nitric Oxide; D008706:Methemoglobin; D006152:Cyclic GMP