title: Inhaled nitric oxide combined with prostacyclin and adrenomedullin in acute respiratory failure with pulmonary hypertension in piglets.
abstract: Our aim was to evaluate if the combined inhalation of both nitric oxide (iNO) and aerosolized prostacyclin or iNO and adrenomedullin (ADM) is more effective in lowering pulmonary arterial pressure (PAP) and improving oxygenation than nitric oxide alone in an animal model with pulmonary hypertension (PH). Moreover, we studied the effect on pulmonary mechanics, surfactant activity, and pulmonary oxidative stress of the different treatments. Twenty-eight piglets with acute lung injury induced by lung lavages with saline were randomized to receive nitric oxide, nitric oxide plus prostacyclin, nitric oxide plus ADM or saline, after. Dynamic compliance, tidal volume, and airway resistance were measured. Lung tissue oxidation was evaluated by measuring total hydroperoxide and advanced oxidation protein products in bronchial aspirate samples. Surface surfactant activity was studied using Capillary Surfactometer. Inhaled nitric oxide combined with prostacyclin or ADM was more effective than nitric oxide alone in lowering PAP and improving oxygenation. Nitric oxide alone or combined increased lung compliance and tidal volume, and decreased airway resistance. No effects on surfactant surface activity and lung tissue oxidation were observed. The treatment with nitric oxide alone or combined with prostacyclin or ADM were effective in decreasing mean PAP and improving oxygenation in a piglet model of PH. However, nitric oxide plus prostacyclin and nitric oxide plus ADM were more effective than nitric oxide alone. The combination of aerosolized prostacyclin and ADM with nitric oxide might have a role in the treatment of infants with PH refractory to nitric oxide alone.
authors: Department of Surgical and Medical Critical Care, Section of Neonatology, Careggi University Hospital of Florence, Florence, Italy. cdani@unifi.it
authors: Carlo
authors: C
authors: Dani
authors: Vittorio
authors: V
authors: Pavoni
authors: Iuri
authors: I
authors: Corsini
authors: Mariangela
authors: M
authors: Longini
authors: Gabriele
authors: G
authors: Gori
authors: Lara
authors: L
authors: Giannesello
authors: Avio
authors: A
authors: Perna
authors: Gaetano
authors: G
authors: Gritti
authors: Ferdinando
authors: F
authors: Paternostro
authors: Annalisa
authors: A
authors: Forestieri
authors: Giuseppe
authors: G
authors: Buonocore
authors: Firmino F
authors: FF
authors: Rubaltelli
mesh_terms: D000280:Administration, Inhalation; D053607:Adrenomedullin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011663:Pulmonary Surfactants; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D012129:Respiratory Function Tests; D034421:Sus scrofa; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D011663:Pulmonary Surfactants; D014665:Vasodilator Agents; D053607:Adrenomedullin; D009569:Nitric Oxide; D011464:Epoprostenol