Protection of lung tissue against ischemia/reperfusion injury by preconditioning with inhaled nitric oxide in an in situ pig model of normothermic pulmonary ischemia.
Topical administration of nitric oxide (NO) by inhalation is currently used as therapy in various pulmonary diseases, but preconditioning with NO to ameliorate lung ischemia/reperfusion (I/R) injury has not been fully evaluated. In this study, we investigated the effects of NO inhalation on functional pulmonary parameters using an in situ porcine model of normothermic pulmonary ischemia. After left lateral thoracotomy, left lung ischemia was maintained for 90 min, followed by a 5h reperfusion period (group I, n = 7). In group II (n = 6), I/R was preceded by inhalation of NO (10 min, 15 ppm). Animals in group III (n = 7) underwent sham surgery without NO inhalation or ischemia. In order to evaluate the effects of NO preconditioning, lung functional and hemodynamic parameters were measured, and the zymosan-stimulated release of reactive oxygen species in arterial blood was determined. Animals in group I developed significant pulmonary I/R injury, including pulmonary hypertension, a decreased pO(2) level in pulmonary venous blood of the ischemic lung, and a significant increase of the stimulated release of reactive oxygen species. All these effects were prevented, or the onset (release of reactive oxygen species) was delayed, by NO inhalation. These results indicate that preconditioning by NO inhalation before lung ischemia is protective against I/R injury in the porcine lung.
Waldow
Thomas
T
Herzzentrum Dresden GmbH, Universitätsklinikum Carl Gustav Carus, 01307 Dresden, Germany. wolfgang.witt@mailbox.tu-dresden.de
Alexiou
Konstantin
K
Witt
Wolfgang
W
Wagner
Florian M
FM
Kappert
Utz
U
Knaut
Michael
M
Matschke
Klaus
K
D000280:Administration, Inhalation; D000818:Animals; D006439:Hemodynamics; D007511:Ischemia; D019194:Ischemic Preconditioning; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology; D009569:Nitric Oxide / Q000008:administration & dosage*; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine
D017382:Reactive Oxygen Species; D009569:Nitric Oxide