title: Effects of intermittent nebulization of NONOate, DPTA/NO, on group B Streptococcus-induced pulmonary hypertension in newborn piglets.
abstract: BACKGROUND
  A single dose of NONOate attenuates pulmonary hypertension (PH) induced by group B Streptococcus (GBS) infusion and this is accompanied by a decrease in systemic vascular resistance (SVR).
  
  
  OBJECTIVE
  The objective of the study was to determine whether two doses of the NONOate sustain the attenuation in GBS-induced PH without further systemic compromise.
  
  
  METHODS
  15 anesthetized newborn piglets were randomized to receive placebo (n = 8) or two doses of nebulized DPTA/NO (n = 7) at 15 and 75 min after GBS-induced PH. Pulmonary artery (Ppa) and systemic (Psa) pressures, cardiac output (CO) and arterial blood gases were obtained at baseline and every 15 min until 180 min during GBS infusion.
  
  
  RESULTS
  Ppa and pulmonary vascular resistance (PVR) decreased significantly after the first dose of nebulized DPTA/NO and this effect was maintained after the second dose. Psa and SVR decreased after the first dose of DPTA/NO to values close to baseline and no further changes in systemic circulation were observed with repeated treatment. PVR/SVR increased with GBS infusion, but decreased after the first dose of DPTA/NO and remained significantly lower for 180 min. CO was significantly higher in the DPTA/NO group. Changes in Ppa, PVR, Psa, SVR, and CO with GBS infusion were not modified by placebo infusion. PaCO(2), base deficit, and pH did not differ between groups. PaO(2) was significantly lower in the DPTA/NO group after the second dose.
  
  
  CONCLUSIONS
  These data demonstrated that GBS-induced PH is attenuated with two doses of DPTA/NO without significant systemic effect. The vasodilatory effect is more pronounced in the pulmonary than in the systemic vasculature, as suggested by lower PVR/SVR in the DPTA/NO group. We speculate that NONOates may have a clinical application in the management of PH in neonates.
authors.affiliation: Department of Pediatrics, R-131, University of Miami School of Medicine, Miami, Fla 33101, USA.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Dabrowska
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hehre
authors.forename: John
authors.initials: J
authors.lastname: Ladino
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bancalari
authors.forename: Cleide
authors.initials: C
authors.lastname: Suguihara
mesh_terms: D000280:Administration, Inhalation; D000475:Alkenes / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D009330:Nebulizers and Vaporizers; D009569:Nitric Oxide / Q000008:administration & dosage*; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D013290:Streptococcal Infections / Q000150:complications / Q000188:drug therapy*; D013292:Streptococcus agalactiae; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000475:Alkenes; D020030:Nitric Oxide Donors; C453079:dipropylenetriamine-NONOate; D009569:Nitric Oxide