Effect of inhaled nitric oxide on pulmonary function after sepsis in a swine model.
BACKGROUND
Inhaled nitric oxide (NO) has been shown to improve sepsis induced pulmonary dysfunction. This study evaluated the mechanism by which inhaled NO improves pulmonary function in a porcine sepsis model.


METHODS
After an infusion of Escherichia coli lipopolysaccharide (LPS, 200 micrograms/kg), animals were resuscitated with saline solution (1 ml/kg/min) and observed for 3 hours while mechanically ventilated (fraction of inspired oxygen, 0.6; tidal volume, 12 ml/kg; positive end-expiratory pressure, 5 cm H2O). Group 1 (LPS, n = 6) received no additional treatment. Group 2 (NO, n = 6) received inhaled NO (40 ppm) for the last 2 hours. Group 3 (control, n = 5) received only saline solution without LPS. Cardiopulmonary variables and blood gases were measured serially. Multiple inert gas elimination technique was performed at 3 hours. Wet to dry lung weight ratio was measured after necropsy.


RESULTS
Lipopolysaccharide resulted in pulmonary arterial hypertension, pulmonary edema, and hypoxemia. Multiple inert gas elimination technique analysis indicated a significant increase in blood flow to true shunt and high ventilation perfusion distribution (VA/Q) areas with an increased dispersion of VA/Q distribution. All of these changes were significantly attenuated by NO.


CONCLUSIONS
Inhaled NO significantly improved LPS induced VA/Q mismatching by decreasing both true shunt and high VA/Q areas, by decreasing pulmonary edema, and by redistributing blood flow from true shunt to ventilated areas.
Ogura
H
H
U.S. Army Institute of Surgical Research, Fort Sam Houston, TX 78234-5012.
Cioffi
W G
WG
Offner
P J
PJ
Jordan
B S
BS
Johnson
A A
AA
Pruitt
B A
BA
D000280:Administration, Inhalation; D000818:Animals; D001424:Bacterial Infections / Q000503:physiopathology*; D004926:Escherichia coli / Q000472:pathogenicity*; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine
D008070:Lipopolysaccharides; D009569:Nitric Oxide