Inhaled nitric oxide attenuates reperfusion inflammatory responses in humans

Mali Mathru, Ruksana Huda, Daneshvari R. Solanki, Stephen Hays, John D. Lang

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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-κB 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 κB 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.

Original languageEnglish (US)
Pages (from-to)275-282
Number of pages8
JournalAnesthesiology
Volume106
Issue number2
DOIs
StatePublished - Feb 2007

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Reperfusion
Nitric Oxide
Tourniquets
P-Selectin
Nitrites
Nitrates
Ischemia
Inflammation
Lipid Peroxides
Quadriceps Muscle
Biological Availability
Lower Extremity
Knee
Oxidative Stress
Anti-Inflammatory Agents
Biopsy
Muscles
Lung
Control Groups
Skin

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Inhaled nitric oxide attenuates reperfusion inflammatory responses in humans. / Mathru, Mali; Huda, Ruksana; Solanki, Daneshvari R.; Hays, Stephen; Lang, John D.

In: Anesthesiology, Vol. 106, No. 2, 02.2007, p. 275-282.

Research output: Contribution to journalArticle

Mathru, M, Huda, R, Solanki, DR, Hays, S & Lang, JD 2007, 'Inhaled nitric oxide attenuates reperfusion inflammatory responses in humans', Anesthesiology, vol. 106, no. 2, pp. 275-282. https://doi.org/10.1097/00000542-200702000-00015
Mathru, Mali ; Huda, Ruksana ; Solanki, Daneshvari R. ; Hays, Stephen ; Lang, John D. / Inhaled nitric oxide attenuates reperfusion inflammatory responses in humans. In: Anesthesiology. 2007 ; Vol. 106, No. 2. pp. 275-282.
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