Combined effects of nitric oxide and hyperoxia on surfactant
function and pulmonary inflammation.
Robbins, Carolyn G., Jonathan M. Davis, T. Allen Merritt, John D.
Amirkhanian, Namita Sahgal, Frederick C. Morin Iii, Stuart Horowitz.
Department of Pediatrics (Neonatology) and the CardioPulmonary
Research Institute, Winthrop-University Hospital, SUNY at Stony Brook
School of Medicine, Mineola, New York 11501; Division of Neonatology,
University of California at Davis, Sacramento, California 95817;
Children's Hospital and State University of New York at Buffalo,
Buffalo, New York 14222
APStracts 2:0107L, 1995.
NO and its derivative ONOO- are potent free radicals that can cause
cell damage, especially in the presence of O2. To determine the
potential pulmonary toxicities of NO and ONOO- in vitro,
Survanta(R)(2.5mg/ml) was exposed to ONOO- (0.3-8mM) in the presence
of two different buffering systems (HEPES and phosphate buffer) and
minimum surface tension (MST) was determined with an oscillating
bubble surfactometer. Significant increases in MST were seen only
with exposure to 8 mM ONOO-, indicating that in vitro, high
concentrations of ONOO- can inhibit natural surfactant function. The
in vivo effects of NO and hyperoxia were then studied in 4 groups of
newborn piglets ventilated for 48 h with 21%O2, 100%O2, 21%O2 and
100ppm NO or with 90% O2 and 100ppm NO. Five animals served as an
untreated control group. Bronchoalveolar lavage fluid (BAL) obtained
at 48 h was subjected to centrifugation and the surfactant pellet was
reconstituted to 5 mg phospholipid/ml. Significant increases in MST
were seen in surfactant from piglets ventilated with NO and 90% O2
compared to either untreated controls or piglets ventilated with 21%
O2 for 48 h (p < 0.05, ANOVA). Significant increases in
neutrophil chemotactic activity (NCA) of BAL were also found in the
NO and O2 group (p < 0.05) with significant positive interaction
between NO and O2 found (p < 0.01). These data indicate that
inhaled NO, in vivo, in the presence of hyperoxia, causes significant
surfactant dysfunction and early evidence of pulmonary inflammation.
This suggests that NO therapy may exacerbate pulmonary O2 toxicity.
Received 2 February 1995; accepted in final form 1 June 1995.
APS Manuscript Number L35-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.