title: The effect of a nebulized NO donor, DPTA/NO, on acute hypoxic pulmonary hypertension in newborn piglets.
abstract: NONOates, novel NO donors, are complexes of NO with nucleophiles which spontaneously and nonenzymatically release NO in aqueous solution. This study sought to determine the cardiopulmonary effects of the nebulized NONOate dipropylenetriamine (DPTA)/NO in newborn piglets with acute hypoxia-induced pulmonary hypertension. Twenty sedated and mechanically ventilated piglets (4-10 days old) exposed to hypoxia (Fi(O2) = 0.14) were randomly assigned to receive nebulized saline as placebo (PL) or DPTA/NO (75 mg) after 30 min of hypoxia. Pulmonary artery (P(pa)) and wedge pressures, systemic (P(sa)) and right atrial pressures, cardiac output (CO) and arterial blood gas were measured at baseline and every 15 min for 2 h. Methemoglobin levels were measured at baseline and 1 h after drug nebulization. Data (means +/- SD) were analyzed by repeated-measures analysis of variance. Acute hypoxia resulted in an increase in P(pa) and pulmonary vascular resistance (PVR), which was significantly attenuated by DPTA/NO nebulization as compared to the PL group (p < 0.0001). Changes in P(sa), CO, systemic vascular resistance (SVR), arterial blood gas and methemoglobin levels were not different between groups. In contrast to the increase in PVR/SVR observed during hypoxia in the PL group, there was a significant decrease in this ratio after NONOate administration (p < 0.0001). These data show that acute hypoxic pulmonary hypertension in newborn piglets is markedly attenuated by NONOate nebulization. This response is predominantly in the pulmonary vasculature as the PVR/SVR was significantly lower in the treated group. We speculate that NONOates may have clinical application in the treatment of persistent pulmonary hypertension of the newborn.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Miami School of Medicine, Miami, FL 33101, USA.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Young
authors.forename: John
authors.initials: J
authors.lastname: Ladino
authors.forename: Cristina
authors.initials: C
authors.lastname: Navarrete
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dabrowska
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hehre
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bancalari
authors.forename: Cleide
authors.initials: C
authors.lastname: Suguihara
mesh_terms: D000208:Acute Disease; D000475:Alkenes / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D009330:Nebulizers and Vaporizers; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D011897:Random Allocation; D012129:Respiratory Function Tests; D013552:Swine
chemical_list: D000475:Alkenes; D020030:Nitric Oxide Donors; C453079:dipropylenetriamine-NONOate