The pulmonary effect of nitric oxide synthase inhibition following endotoxemia in a swine model.
OBJECTIVE
To evaluate the pulmonary effect of treatment with N-nitro-L-arginine methyl ester (NAME) with and without inhaled nitric oxide (NO) in a swine model of endotoxemia.


METHODS
Randomized controlled trial.


METHODS
Laboratory.


METHODS
Following a 20-minute intravenous infusion of Escherichia coli lipopolysaccharide (LPS) (200 micrograms/kg), animals were resuscitated with saline solution (1 mL/kg per minute) and observed for 3 hours while mechanically ventilated (fraction of inspired oxygen [FIO2], 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 (NAME, n = 5) received NAME (3 mg/kg per hour) for the last 2 hours; group 3 (NO, n = 6) received NAME (3 mg/kg per hour) and inhaled NO (40 ppm) for the last 2 hours; and group 4 (control, n = 5) received only saline solution without LPS.


METHODS
Cardiopulmonary variables and blood gases were measured serially. The multiple inert gas elimination technique was performed at 3 hours. The wet-to-dry lung weight ratio was measured following necropsy.


RESULTS
Administration of LPS resulted in pulmonary arterial hypertension, pulmonary edema, and hypoxemia with increased ventilation perfusion ratio mismatching. None of these changes were attenuated by NAME treatment alone but all were significantly improved by the simultaneous administration of inhaled NO.


CONCLUSIONS
Systemic NO synthase inhibition failed to restore hypoxic pulmonary vasoconstriction following LPS administration. The deleterious effects of endotoxemia on pulmonary function can be improved by inhaled NO but not by systemic inhibition of NO synthase.
Ogura
H
H
US Army Institute of Surgical Research, Department of Critical Care, Brooke Army Medical Center, Fort Sam Houston, Tex.
Offner
P J
PJ
Saitoh
D
D
Jordan
B S
BS
Johnson
A A
AA
Pruitt
B A
BA
Cioffi
W G
WG
D000280:Administration, Inhalation; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016470:Bacteremia / Q000150:complications*; D001784:Blood Gas Analysis; D001794:Blood Pressure; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000150:complications*; D005260:Female; D006976:Hypertension, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D000860:Hypoxia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D008176:Lung Volume Measurements; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D011669:Pulmonary Wedge Pressure; D011897:Random Allocation; D013552:Swine
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester