Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation
Open accessAbstract
Ischemia/reperfusion (IR) injury in transplanted livers contributes to organ dysfunction and failure and is characterized in part by loss of NO bioavailability. Inhalation of NO is nontoxic and at high concentrations (80 ppm) inhibits IR injury in extrapulmonary tissues. In this prospective, blinded, placebo-controlled study, we evaluated the hypothesis that administration of inhaled NO (iNO; 80 ppm) to patients undergoing orthotopic liver transplantation inhibits hepatic IR injury, resulting in improved liver function. Patients were randomized to receive either placebo or iNO (n = 10 per group) during the operative period only. When results were adjusted for cold ischemia time and sex, iNO significantly decreased hospital length of stay, and evaluation of serum transaminases (alanine transaminase, aspartate aminotransferase) and coagulation times (prothrombin time, partial thromboplastin time) indicated that iNO improved the rate at which liver function was restored after transplantation. iNO did not significantly affect changes in inflammatory markers in liver tissue 1 hour after reperfusion but significantly lowered hepatocyte apoptosis. Evaluation of circulating NO metabolites indicated that the most likely candidate transducer of extrapulmonary effects of iNO was nitrite. In summary, this study supports the clinical use of iNO as an extrapulmonary therapeutic to improve organ function following transplantation.
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Nitric oxide inhalation is used in infants with primary pulmonary hypertension of the newborn to reduce pulmonary artery pressure.
“It is used in infants with primary pulmonary hypertension of the newborn to reduce pulmonary artery pressure.158”
From Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care (2010) · cites this paper as [158]
The Introduction says inhaled NO has been used clinically to reduce pulmonary artery pressures, but describes patients with inflammatory-mediated lung injury. It does not specify infants or primary pulmonary hypertension of the newborn; the study itself enrolled adults undergoing liver transplantation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredInhaled NO therapy before liver transplantation significantly elevates tissue nitrite levels that are associated with cytoprotection.
“A previous study from Lang et al demonstrated that inhaled NO therapy before liver transplanation significantly elevated tissue nitrite levels that were associated with cytoprotection [166].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [166]
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- Authors
- 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., Cross, R. C., Frenette, L., Kelley, E. E., Wilhite, D. W., Hall, C. R., Page, G. P., Fallon, M. B., Bynon, J. S., Eckhoff, D. E., & Patel, R. P.
- Affiliations
- University of Washington (US)
- University of Alabama at Birmingham (US)
- University of Pittsburgh (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2007-09-04
- Volume
- 117
- Issue
- 9
- Pages
- 2583-2591
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1950460
- OpenAlex
- W2016928245
- Cited by
- 224
- References
- 44
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 10 · 2018: 6 · 2017: 16 · 2016: 10 · 2015: 24 · 2014: 18 · 2013: 9 · 2012: 23
- FWCI
- 18.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- Topics
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- inhaled nitric oxide, orthotopic liver transplantation, ischemia-reperfusion injury, liver function recovery, nitric oxide bioavailability, hepatocyte apoptosis, nitrite, transaminases, coagulation, length of hospital stay, inflammatory markers
- MeSH terms
- Administration, Inhalation, Adult, Aged, Female, Humans, Length of Stay, Liver, Male, Middle Aged, Nitric Oxide, Reperfusion Injury, Liver Transplantation, Cell Death, Reactive Oxygen Species
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