Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers.
Nitric oxide (NO) is believed to be involved in the pathophysiology of sepsis. This study evaluated the activity of the NO pathway in a human endotoxin model. At baseline and after endotoxin, on-line measurements of exhaled NO (eNO) were made using a chemiluminescence technique with a single-breath method. NO-free air was inhaled prior to exhalation against a resistance. NO in orally and nasally exhaled air and in rectal gas was investigated. Plasma nitrite, nitrate, and guanosine 3', 5'-monophosphate (cGMP) and the events after diclophenac administration were also studied. Endotoxin infusion resulted in tachycardia and fever. An early increase in oral eNO concentration was observed and oral eNO decreased after diclophenac administration. NO exhaled nasally, NO in rectum gas and nitrite/nitrate levels remained unchanged over the study period, cGMP increased after 4 h. These findings suggest an early increase in nitric oxide production from the lungs, probably due to increased activity of the constitutive nitric oxide synthase upon endotoxin stimulation. In contrast, nitric oxide production in the upper airways, measured as nasally exhaled nitric oxide and nitric oxide in rectal gas, remained unchanged. Further studies will elucidate if exhaled nitric oxide is a valuable marker of sepsis-induced lung injury and if monitoring of treatment is possible.
Soop
A
A
Dept of Anaesthesiology and Intensive Care, Center for Surgical Sciences, Huddinge University Hospital, Stockholm, Sweden. anne.soop@anaesth.hs.sll.se
Sollevi
A
A
Weitzberg
E
E
Lundberg
J O N
JO
Palm
J
J
Albert
J
J
D000328:Adult; D000704:Analysis of Variance; D006152:Cyclic GMP / Q000097:blood*; D004731:Endotoxins / Q000008:administration & dosage*; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008163:Luminescent Measurements; D008168:Lung / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology
D004731:Endotoxins; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D006152:Cyclic GMP