Increased nitric oxide in exhaled gas as an early marker of lung inflammation in a model of sepsis.
Nitric Oxide (NO) has been implicated in the pathologic vasodilation of sepsis. Because NO can be measured in the exhaled gas of animals and humans, we hypothesized that increases in exhaled NO would occur in a septic model. Using a blinded design, 10 male Sprague-Dawley rats (300 to 400 g) were anesthetized, paralyzed, tracheotomized, and randomized (5/group) to receive an intravenous injection of either lipopolysaccharide (LPS) (Salmonella typhosa, 20 mg/kg) or placebo (equal volume of saline). Thereafter, exhaled gas was collected and measurements of NO concentration were made using chemiluminescence every 20 min for 300 min during ventilation (RR 40 breaths/min, VT 3 ml; PEEP 0, FIO2 0.21). Another group of 10 animals (5 LPS; 5 control) were treated in the same fashion and then killed at 240 min and an arterial blood sample obtained for blood gas and TNF alpha determinations. Pressure volume (PV) curves were constructed and lungs removed, preserved, and submitted for histologic evaluation. LPS-treated rats had lower mean arterial pressures than the control group, p < 0.0001. No significant differences in static lung compliance and PV curves were found in the two groups. TNF alpha levels were greater in the LPS group (1.40 +/- 0.24 ng/ml) versus control group (0.09 +/- 0.04 ng/ml), p < 0.001. By contrast to the control group, exhaled NO concentration rose in all LPS-treated rats at approximately 100 min and at about 160 min reached a plateau that was 6 times greater than control levels (p < 0.0001). There was greater interstitial, airspace, and total lung injury in the LPS group (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Stewart
T E
TE
Department of Medicine, Samuel Lunenfeld Research Institute Mount Sinai Hospital, Toronto, Ontario, Canada.
Valenza
F
F
Ribeiro
S P
SP
Wener
A D
AD
Volgyesi
G
G
Mullen
J B
JB
Slutsky
A S
AS
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002245:Carbon Dioxide / Q000097:blood; D004311:Double-Blind Method; D008070:Lipopolysaccharides; D008163:Luminescent Measurements; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism; D019001:Nitric Oxide Synthase; D010100:Oxygen / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D012485:Salmonella typhi; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015415:Biomarkers; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; D010100:Oxygen