Inhaled nitric oxide attenuates reperfusion inflammatory responses in humans.
BACKGROUND
Reduced bioavailability of endothelium-derived nitric oxide associated with reperfusion could potentially exacerbate the inflammatory response during reperfusion. Evidence suggests the pharmacologic effects of inhaled nitric oxide may extend beyond the pulmonary vasculature, and this is attributed to nitric oxide-derived complexes in blood that ultimately orchestrate antiinflammatory effects. In this study, the authors evaluated the potential for inhaled nitric oxide (80 ppm) to attenuate inflammation instigated by ischemia-reperfusion in a human model using patients undergoing knee surgery where a tourniquet was used to produce a bloodless surgical field.


METHODS
Inhaled nitric oxide (80 ppm) was administered before tourniquet application and continued throughout reperfusion until the completion of surgery. Venous blood samples were collected before and after reperfusion, for the measurements of nitrate and nitrite, CD11b/CD18, soluble P-selectin, and lipid hydroperoxide. Muscle biopsies were obtained from the quadriceps muscle before skin closure and analyzed for myeloperoxide, conjugated dienes, and nuclear factor-kappaB translocation.


RESULTS
Administration of inhaled nitric oxide (80 ppm) significantly attenuated the inflammatory response characterized by reduced expression of CD11b/CD18, P-selectin, and nuclear factor kappaB compared with the control group. This was accompanied by increased plasma levels of nitrate and nitrite and reduced oxidative stress.


CONCLUSIONS
Administration of inhaled nitric oxide at 80 ppm significantly reduces inflammation in lower extremity ischemia-reperfusion in humans. This observation supports the concept that during diseases characterized by dysfunction in nitric oxide metabolism, inhaled nitric oxide may be an effective therapy to replenish systemic nitric oxide, thus retarding inflammatory-mediated injury.
Mathru
Mali
M
Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama 35249-6810, USA. mamathru@uab.edu
Huda
Ruksana
R
Solanki
Daneshvari R
DR
Hays
Stephen
S
Lang
John D
JD
D000280:Administration, Inhalation; D000328:Adult; D005260:Female; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D008054:Lipid Peroxides / Q000097:blood; D035002:Lower Extremity / Q000098:blood supply*; D016177:Macrophage-1 Antigen / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000008:administration & dosage*; D019007:P-Selectin / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D015424:Reperfusion / Q000009:adverse effects*
D008054:Lipid Peroxides; D016177:Macrophage-1 Antigen; D016328:NF-kappa B; D009566:Nitrates; D019007:P-Selectin; D009569:Nitric Oxide; D009195:Peroxidase