title: Endothelin-1 influences the efficacy of inhaled nitric oxide in experimental acute lung injury.
abstract: Beneficial effects of inhaled nitric oxide (iNO) on arterial oxygenation in acute lung injury (ALI) suggest the presence of vasoconstriction in ventilated lung regions and this may be influenced by endothelin-1 (ET-1). We studied a possible interaction between ET-1 and iNO in experimental ALI. Sixteen piglets were anesthetized and mechanically ventilated (inspired O2 fraction, 1.0). After induction of ALI by surfactant depletion, animals were randomly assigned to either inhale 30 ppm NO (iNO group, n = 8), or to receive no further intervention (controls, n = 8). Measurements were performed during the following 4 hrs. In all animals, induction of ALI significantly decreased arterial oxygen tension (PaO2) from 569 +/- 15 (prelavage) to 58 +/- 3 mm Hg. Inhaled NO significantly increased PaO2 when compared with controls (iNO group: 265 +/- 51 mm Hg; controls: 50 +/- 4 mm Hg, values at 4 hrs, P < 0.01). Prelavage ET-1 plasma levels were comparable between groups (iNO: 0.74 +/- 0.03, controls: 0.71 +/- 0.03 fmol/ml, NS). During the protocol, the ET-1 levels increased and were different at 3 hrs (iNO: 0.93 +/- 0.06, controls: 1.25 +/- 0.09 fmol/ml; P < 0.05). PaO2 changes induced by iNO revealed a moderate and significant correlation with ET-1 plasma levels (R = 0.548, P = 0.001). Our data suggest that endogenous ET-1 production influences the efficacy of iNO in ALI. Furthermore, iNO reduced ET-1 plasma levels, possibly indicating anti-inflammatory properties of iNO in the early phase of ALI.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Charité, Campus Virchow-Klinikum, University Medical Center, Berlin, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Busch
authors.forename: Bodil
authors.initials: B
authors.lastname: Petersen
authors.forename: Maria
authors.initials: M
authors.lastname: Deja
authors.forename: Bernd
authors.initials: B
authors.lastname: Donaubauer
authors.forename: Sven
authors.initials: S
authors.lastname: Laudi
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jaumann
authors.forename: Sven
authors.initials: S
authors.lastname: Bercker
authors.forename: Willehad
authors.initials: W
authors.lastname: Boemke
authors.forename: Udo
authors.initials: U
authors.lastname: Kaisers
mesh_terms: D000208:Acute Disease; D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury; D009569:Nitric Oxide / Q000008:administration & dosage / Q000378:metabolism*; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D011897:Random Allocation; D013552:Swine
chemical_list: D019332:Endothelin-1; D009569:Nitric Oxide