title: Effect of modulators of hypoxic pulmonary vasoconstriction on the response to inhaled nitric oxide in a neonatal model of severe pulmonary atelectasis.
abstract: Hypoxic pulmonary vasoconstriction (HPV) is an intrinsic mechanism that facilitates ventilation to perfusion matching and preservation of oxygenation. We investigated the neonatal HPV response from extensive atelectasis and tested the hypothesis that (I) the resulting hypoxemia is corrected by inhaled nitric oxide (NO); (2) the "pulmonary steal" of blood away from hypoxic area is further improved by modulators of the HPV. Intratracheal injection of steel beads in 32 piglets (7 to 20 days) resulted in atelectasis of 50% to 75% of the lungs. The piglets were then randomized to receive saline (control), indomethacin (IND) 2 mg/kg, doxapram (DOX) 0.5 mg/kg/h or almitrine (ALM) 4 micrograms/kg/min. After 30 minutes, all animals were subjected to NO at 40 ppm. Atelectasis resulted in severe impairment in oxygenation (PaO2 - 105 +/- 6 mm Hg, AaDO2 = 536 +/- 9 mm Hg; shunt fraction = 31% +/- 2%) and moderate pulmonary hypertension. Mean pulmonary artery pressure (PAP) increased to 35 +/- 0.8 mm Hg. NO reduced pulmonary vascular resistance (PVR) from 128 +/- 14 mm Hg/kg/mL/min to 74 +/- 9 mm Hg/kg/mL/min and improved gas exchange (PaO2 = 180 +/- 50 and AaDO2 = 438 +/- 50 mm Hg). Following the development of atelectasis, the peripheral chemoreceptor agonists (ALM and DOX) did not modify gas exchange and had no significant cardiovascular effect. ALM and DOX failed to enhance the response to NO. IND did not alter HPV, but prevented the improvement in gas exchange associated with NO-induced pulmonary vasodilation.
authors.affiliation: Division of Neonatology, University of South Alabama, Mobile, USA.
authors.forename: F G
authors.initials: FG
authors.lastname: Eyal
authors.forename: W E
authors.initials: WE
authors.lastname: Hachey
authors.forename: N L
authors.initials: NL
authors.lastname: Curtet-Eyal
authors.forename: F E
authors.initials: FE
authors.lastname: Kellum
authors.forename: G
authors.initials: G
authors.lastname: Alpan
mesh_terms: D000280:Administration, Inhalation; D000402:Airway Obstruction / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D009569:Nitric Oxide / Q000627:therapeutic use*; D001261:Pulmonary Atelectasis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D009569:Nitric Oxide