Inhaled nitric oxide prevents the increase in pulmonary vascular
permeability caused by hydrogen peroxide.
Poss, W. Bradley, Otwell D. Timmons, Imad S. Farrukh, John R. Hoidal,
and John R. Michael.
Division of Respiratory, Critical Care and Occupational Pulmonary
Medicine, Department of Medicine, Veterans Administration Medical
Center and the University of Utah School of Medicine and the Division
of Pediatric Critical Care, Department of Pediatrics, University of
Utah School of Medicine, Salt Lake City, Utah 84132
APStracts 2:0201A, 1995.
Given the widespread interest in using inhaled nitric oxide (NO.) in
the treatment of acute lung injury and the importance of oxygen
radicals in the pathogenesis of this condition, we studied the
effects, in buffer-perfused isolated rabbit lungs, of inhaled NO. (24
parts per million) on the oxidant lung injury caused by generating
hydrogen peroxide with glucose and glucose oxidase (GOX). Since
inhaled NO. may affect vascular pressure, experiments were performed
at a constant pulmonary arterial pressure. Infusion of GOX (462.5
mU/ml) substantially increased vascular permeability, as indicated by
an increase in the lung/perfusate 125I-albumin ratio (control 0.041
+/- .007 vs. GOX 0.141 +/- .041, P<0.02), the lavage/perfusate
125I-albumin ratio (control 0.004 +/- .001 vs. GOX 0.054 +/- .016,
P<0.003) and the change in pulmonary vascular filtration
coefficient (Kf,c) after 30 minutes of perfusion (_ Kf,c, control
-1.4 +/- 1.2 vs. GOX 9.5 +/- 3.7 ml/mmHg. min.100 gm dry lung weight,
P<0.01). Perfusion with GOX also increased wet/dry lung weight
(control 7.7 +/- 1 vs. GOX 11.4 +/- 1, P<0.001). Lungs treated with
inhaled NO. before perfusion with GOX had lung/perfusate and
lavage/perfusate 125I-albumin ratios that were not significantly
different from control values and intermediate between the control
and GOX groups (lung/perfusate ratios: control 0.041 +/- .007, GOX
0.141 +/- .041, and GOX + NO. 0.091 +/- .014, P<0.18 for GOX + NO.
vs control or GOX) and (lavage/perfusate ratios: control 0.004 +/-
.001, GOX 0.054 +/- .016 vs. GOX + NO. 0.027 +/- .006, P<0.12 for
GOX + NO. vs control and P<0.07 GOX + NO. vs GOX). Treatment with
inhaled NO. prevented the increase in Kf,c caused by GOX (_ Kf,c
after 30 minutes, GOX 9.5 +/- 3.7 vs. GOX + NO. 1.3 +/- 0.8
ml/mmHg.min.100.gm dry lung weight, P<0.05) and eliminated the
increase in wet/dry lung weight produced by GOX (GOX 11.4 +/- 1 vs.
GOX + NO. 7.8 +/- 1, P<0.01). Thus, inhaled NO. substantially
reduced the increase in pulmonary vascular permeability caused in the
isolated lung by the intravascular generation of hydrogen peroxide.
Received 20 October 1994; accepted in final form 5 May 1995.
APS Manuscript Number A1079-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.