Inhaled Nitric Oxide Attenuates Reperfusion Inflammatory Responses in Humans
Open accessAbstract
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.
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Inhalation of nitric oxide does not only vasodilate pulmonary vessels but has also distant effects.
“It is noteworthy that inhalation of nitric oxide does not only vasodilate pulmonary vessels but has also distant effects.159,160”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [159]
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Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans
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Enhanced <i>S</i> -Nitroso-Albumin Formation From Inhaled NO During Ischemia/Reperfusion
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“cept that replenishing nitric oxide may provide an efficacious therapy in ischemia–reperfusion injury.(10) In this”
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Lang, J. D., Teng, X., Chumley, P., Crawford, J. H., Isbell, T. S., Chacko, B. K., Liu, Y., Jhala, N., Crowe, D. R., Smith, A. B., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31892 · Cited by 224 · see citing works
Self-citationTherapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases
Omar, S. A., Webb, A. J., Lundberg, J. O., & Weitzberg, E. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12441 · Cited by 175 · see citing works
NO generation from inorganic nitrate and nitrite: Role in physiology, nutrition and therapeutics
Lundberg, J. O., & Weitzberg, E. (2009) · Archives of Pharmacal Research · doi:10.1007/s12272-009-1803-z · Cited by 153 · see citing works
Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care
Weitzberg, E., Hezel, M., Lundberg, J. O., & Warner, D. S. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181fcf3cc · Cited by 145 · see citing works
- Authors
- Mathru, M., Huda, R., Solanki, D. R., Hays, S., & Lang, J. D.
- Affiliations
- University of Alabama at Birmingham (US)
- Instructor of Anesthesiology.
- Professor of Anesthesiology, Department of Anesthesiology.
- The University of Texas Medical Branch at Galveston (US)
- University of Washington (US)
- Venue
- Anesthesiology
- Published
- 2007-02-01
- Volume
- 106
- Issue
- 2
- Pages
- 275-282
- ISSN
- 0003-3022 (ISSN-L)
- OpenAlex
- W1980292532
- Cited by
- 84
- References
- 3
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 7 · 2018: 5 · 2017: 6 · 2016: 3 · 2015: 6 · 2014: 8 · 2013: 4 · 2012: 5
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- inhaled nitric oxide, ischemia-reperfusion injury, inflammation, nitric oxide bioavailability, tourniquet, knee surgery, CD11b/CD18, P-selectin, nuclear factor-kappaB, oxidative stress, nitrite/nitrate, conjugated dienes, quadriceps, lower limb ischemia
- MeSH terms
- Administration, Inhalation, Adult, Female, Humans, Inflammation, Lipid Peroxides, Male, Peroxidase, Nitrates, Nitric Oxide, Reperfusion, Macrophage-1 Antigen, NF-kappa B, P-Selectin, Lower Extremity
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