Nebulized nitrite protects rat lung grafts from ischemia reperfusion injury
Open accessAbstract
Objectives Nebulization is a potential method for delivering therapeutic agents to lung grafts. Recent evidence suggests that nitrite may mitigate ischemia-reperfusion injury via a nitric oxide-dependent pathway.Methods Syngeneic orthotopic left lung transplantation was performed in rats after 7 hours of cold ischemia. Sodium nitrite (3 mg) or phosphate-buffered saline (controls) was delivered before procurement via nebulization.Results Nitrite treatment was associated with better oxygenation, lower peak airway pressure, lower wet/dry ratio, reduced myeloperoxidase level and macrophage infiltration, increased cyclic guanosine monophosphate (cGMP) levels, and decreased levels of interleukin 6, interleukin 1-β, inducible nitric oxide synthase, and intercellular adhesion molecule-1 at 2 hours after reperfusion. Treatment with 2-(4-carboxypheny)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a nitric oxide scavenger, reversed the beneficial effects of nitrite and decreased cGMP concentration in grafts. A dose-response curve of nitrite was performed at the following doses: 0.3 mg (N0.1), 3.0 mg (N1.0), 5.25 mg (N1.75), 7.5 mg (N2.5), and 15.0 mg (N5.0). All treatments, excluding N1.0, resulted in poorer oxygenation, higher peak airway pressures, and higher wet/dry ratio. Higher dosage groups (N1.75, N2.5, and N5.0) exhibited positive immunostaining of nitrotyrosine and increased the intensity of nitrotyrosine in immunoblotting.Conclusions These data suggest that nebulized nitrite limits lung ischemia-reperfusion injury and may prove a clinically useful strategy but requires appropriate dosing to limit oxidative injury at high doses.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Nitrite lessens inflammation caused by ischemia in various organs.
“Nitrite also lessens inflammation caused by ischemia in various organs (89, 125, 140, 146, 147, 176, 197)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [140]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Ischemia–Reperfusion–induced Lung Injury
de Perrot, M. E., Liu, M., Waddell, T. K., & Keshavjee, S. H. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200207-670so · Cited by 962 · see citing works
Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
Duranski, M. R., Greer, J. J. M., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W., Patel, R. P., Yet, S.-F., Wang, X., Kevil, C. G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22493 · Cited by 674 · see citing works
Self-citationWebb, A., Bond, R., McLean, P., Uppal, R., Benjamin, N., & Ahluwalia, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402927101 · Cited by 608 · see citing works
Bolli, R. (2001) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2001.1462 · Cited by 597 · see citing works
Shiva, S., Sack, M. N., Greer, J. J., Duranski, M., Ringwood, L. A., Burwell, L., Wang, X., MacArthur, P. H., Shoja, A., Raghavachari, N., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070198 · Cited by 555 · see citing works
Self-citationThe Effect of Primary Graft Dysfunction on Survival after Lung Transplantation
Christie, J. D., Kotloff, R. M., Ahya, V. N., Tino, G., Pochettino, A. A., Gaughan, C., Demissie, E., & Kimmel, S. E. (2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200409-1243oc · Cited by 350 · see citing works
Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator
Hunter, C. J., Dejam, A., Blood, A. B., Shields, H., Kim-Shapiro, D. B., Machado, R. F., Tarekegn, S., Mulla, N., Hopper, A. O., Schechter, A. N., et al. (2004) · Nature Medicine · doi:10.1038/nm1109 · Cited by 281 · see citing works
Self-citationJung, K.-H., Chu, K., Ko, S.-Y., Lee, S.-T., Sinn, D.-I., Park, D.-K., Kim, J.-M., Song, E.-C., Kim, M., & Roh, J.-K. (2006) · Stroke · doi:10.1161/01.str.0000245116.40163.1c · Cited by 253 · see citing works
Inhaled nitric oxide reduces human lung allograft dysfunction
Date, H., Triantafillou, A. N., Trulock, E. P., Pohl, M. S., Cooper, J. D., & Patterson, G. A. (1996) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(96)70364-1 · Cited by 236 · see citing works
Tripatara, P., Patel, N. S. A., Webb, A., Rathod, K., Lecomte, F. M. J., Mazzon, E., Cuzzocrea, S., Yaqoob, M. M., Ahluwalia, A., & Thiemermann, C. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006050450 · Cited by 226 · see citing works
Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics
DEZFULIAN, C., RAAT, N., SHIVA, S., & GLADWIN, M. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.05.001 · Cited by 198 · see citing works
Self-citationSimplified rat lung transplantation using a cuff technique
Mizuta, T., Kawaguchi, A. T., Nakahara, K., & Kawashima, Y. (1989) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(19)34549-0 · Cited by 193 · see citing works
Zuckerbraun, B. S., Shiva, S., Ifedigbo, E., Mathier, M. A., Mollen, K. P., Rao, J., Bauer, P. M., Choi, J. J. W., Curtis, E., Choi, A. M. K., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.891077 · Cited by 192 · see citing works
Self-citationPinsky, D. J., Naka, Y., Chowdhury, N. C., Liao, H., Öz, M. C., Michler, R. E., Kubaszewski, E., Maliñski, T., & Stern, D. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.25.12086 · Cited by 191 · see citing works
Meade, M. O., Granton, J. T., Matte-Martyn, A., McRae, K. M., Weaver, B., Cripps, P., & Keshavjee, S. H. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.2203034 · Cited by 186 · see citing works
Immunological Link Between Primary Graft Dysfunction and Chronic Lung Allograft Rejection
Bharat, A., Kuo, E. Y., Steward, N. S., Aloush, A. A., Hachem, R. R., Trulock, E. P., Patterson, G. A., Meyers, B. F., & Mohanakumar, T. (2008) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2008.03.073 · Cited by 172 · see citing works
Effects of inhaled NO and inhibition of endogenous NO synthesis in oxidant-induced acute lung injury
Kavanagh, B. P., Mouchawar, A. M., Goldsmith, J. A., & Pearl, R. G. (1994) · Journal of Applied Physiology · doi:10.1152/jappl.1994.76.3.1324 · Cited by 133 · see citing works
The role of nitrite in nitric oxide homeostasis: A comparative perspective
Jensen, F. B. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.02.010 · Cited by 112 · see citing works
Alef, M. J., Vallabhaneni, R., Carchman, E., Morris, S. M., Shiva, S., Wang, Y., Kelley, E. E., Tarpey, M. M., Gladwin, M. T., Tzeng, E., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44079 · Cited by 101 · see citing works
Self-citationKohmoto, J., Nakao, A., Stolz, D. B., Kaizu, T., Tsung, A., Ikeda, A., Shimizu, H., Takahashi, T., Tomiyama, K., Sugimoto, R., et al. (2007) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2007.01940.x · Cited by 100 · see citing works
Self-citationNitroprusside Ameliorates Lung Allograft Reperfusion Injury
Yamashita, M., Schmid, R. A., Ando, K., Cooper, J. D., & Patterson, G. A. (1996) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(96)00439-0 · Cited by 62 · see citing works
Nitric Oxide Ventilation of Rat Lungs from Non-Heart-Beating Donors Improves Posttransplant Function
Dong, B., Abano, J. B., & Egan, T. M. (2009) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2009.02840.x · Cited by 54 · see citing works
Effects of Various Timings and Concentrations of Inhaled Nitric Oxide in Lung Ischemia–Reperfusion
Murakami, S., BACHA, E. A., Mazmanian, G., Détruit, H., Chapelier, A. R., Dartevelle, P., & Hervé, P. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.156.2.9608007 · Cited by 51 · see citing works
Naka, Y., Chowdhury, N. C., Öz, M. C., Smith, C. R., Yano, O. J., Michler, R. E., Stern, D. M., & Pinsky, D. J. (1995) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/s0022-5223(95)70380-2 · Cited by 50 · see citing works
Nitrite Reduces Acute Lung Injury and Improves Survival in a Rat Lung Transplantation Model
Sugimoto, R., Okamoto, T., Nakao, A., Zhan, J., Wang, Y., Kohmoto, J., Tokita, D., Farver, C. F., Tarpey, M. M., Billiar, T. R., et al. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04169.x · Cited by 40 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Kapil, V., Khambata, R. S., Jones, D. A., Rathod, K., Primus, C., Massimo, G., Fukuto, J. M., & Ahluwalia, A. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019240 · Cited by 248 · see citing works
Functional acellular matrix for tissue repair
Wang, B., Qinglai, T., Yang, Q., Li, M., Zeng, S., Yang, X., Xiao, Z., Tong, X., Lei, L., & Li, S. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100530 · Cited by 111 · see citing works
Yang, T., Zhang, X., Tarnawski, L., Peleli, M., Zhuge, Z., Terrando, N., Harris, R. A., Olofsson, P. S., Larsson, E., Persson, A. E. G., et al. (2017) · Redox Biology · doi:10.1016/j.redox.2017.06.002 · Cited by 80 · see citing works
Working with nitric oxide and hydrogen sulfide in biological systems
Yuan, S. S., Patel, R. P., & Kevil, C. G. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00327.2014 · Cited by 74 · see citing works
Inorganic nitrite supplementation for healthy arterial aging
Sindler, A. L., DeVan, A. E., Fleenor, B. S., & Seals, D. R. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01100.2013 · Cited by 68 · see citing works
Nitrate/Nitrite as Critical Mediators to Limit Oxidative Injury and Inflammation
Waltz, P., Escobar, D., Botero, A. M., & Zuckerbraun, B. S. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6256 · Cited by 70 · see citing works
Inhaled nitric oxide: Current clinical concepts
Bhatraju, P. K., Crawford, J. H., Hall, M. K., & Lang, J. D. (2015) · Nitric Oxide · doi:10.1016/j.niox.2015.08.007 · Cited by 57 · see citing works
Ormerod, J. O. M., Arif, S., Mukadam, M., Evans, J. D. W., Beadle, R. M., Fernandez, B. O., Bonser, R. S., Feelisch, M., Madhani, M., & Frenneaux, M. P. (2015) · Circulation Heart Failure · doi:10.1161/circheartfailure.114.001716 · Cited by 35 · see citing works
Lung protection by inhalation of exogenous solubilized extracellular matrix
Wu, J., Ravikumar, P., Nguyen, K. T., Hsia, C. C. W., & Hong, Y. (2017) · PLoS ONE · doi:10.1371/journal.pone.0171165 · Cited by 30 · see citing works
Renovascular effects of inorganic nitrate following ischemia-reperfusion of the kidney
Zhang, G., Han, H., Zhuge, Z., Dong, F., Jiang, S., Wang, W., Guimarães, D. D., Schiffer, T. A., Lai, E. Y., Carvalho, L. R. R. A., et al. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101836 · Cited by 27 · see citing works
Redox therapeutics in hepatic ischemia reperfusion injury
Patel, R. P., Lang, J. D., Smith, A. B., & Crawford, J. H. (2014) · World Journal of Hepatology · doi:10.4254/wjh.v6.i1.1 · Cited by 23 · see citing works
Portella, R. D. L., Bickta, J., & Shiva, S. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6260 · Cited by 21 · see citing works
Kumar, A., Noda, K., Philips, B. J., Velayutham, M., Stolz, D. B., Gladwin, M. T., Shiva, S., & D’Cunha, J. (2020) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00367.2018 · Cited by 18 · see citing works
Self-citationPretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model
Shih, P.-K., Cheng, C.-M., Li, H., Huang, M.-F., Chiu, C., Chen, J.-X., Chen, N.-W., & Chou, S. (2013) · Journal of Surgical Research · doi:10.1016/j.jss.2013.07.010 · Cited by 16 · see citing works
Yingchoncharoen, T., Rakyhao, T., Chuncharunee, S., Sritara, P., Pienvichit, P., Paiboonsukwong, K., Sathavorasmith, P., Sirirat, K., Sriwantana, T., Srihirun, S., et al. (2017) · Nitric Oxide · doi:10.1016/j.niox.2017.09.010 · Cited by 15 · see citing works
Tawa, M., Furukawa, T., Tongu, H., Sugihara, M., Taguwa, S., Yamanaka, M., Yano, Y., Matsumori, H., Kitada, R., Sawano, T., et al. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.04.045 · Cited by 12 · see citing works
Direct Peritoneal Resuscitation Alters Leukocyte Infiltration in the Lung After Acute Brain Death
Weaver, J. L., Matheson, P. J., Matheson, A., Downard, C. D., Garrison, R. N., & Smith, J. W. (2017) · Shock · doi:10.1097/shk.0000000000001069 · Cited by 9 · see citing works
How can we improve the quality of transplantable lungs?
Levin, K., Kotecha, S., Westall, G. P., & Snell, G. I. (2016) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2016.1240035 · Cited by 7 · see citing works
Saberi, S., Najafipour, H., Rajizadeh, M. A., Etminan, A., Jafari, E., & Iranpour, M. (2024) · BMC Nephrology · doi:10.1186/s12882-024-03824-3 · Cited by 7 · see citing works
Nitrate and Nitrite in Aging and Age-Related Disease
Johnson, L. C., DeVan, A. E., Justice, J. N., & Seals, D. R. (2017) · Springer eBooks · doi:10.1007/978-3-319-46189-2_18 · Cited by 5 · see citing works
Lung Ischemia–Reperfusion Injury in Lung Transplant Surgery: Where Do We Stand?
Berzenji, L., Hendriks, J. M., Verleden, S. E., Yogeswaran, S. K., Wen, W., Lauwers, P., Verleden, G. M., Paep, R. D., Mertens, P., Rodrigus, I. E. R., et al. (2025) · Antioxidants · doi:10.3390/antiox14111295 · Cited by 4 · see citing works
- Authors
- Okamoto, T., Tang, X., Janocha, A., Farver, C. F., Gladwin, M. T., & McCurry, K. R.
- Affiliations
- Cleveland Clinic (US)
- University of Pittsburgh (US)
- Corresponding author
- McCurry, Kenneth R.
- Venue
- The Journal of Thoracic and Cardiovascular Surgery
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 145
- Issue
- 4
- Pages
- 1108-1116.e1
- ISSN
- 0022-5223 (ISSN-L)
- OpenAlex
- W2168494714
- Cited by
- 22
- References
- 25
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2020: 3 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 1
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic and Cardiovascular Surgery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000439)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- sodium nitrite, lung transplantation, ischemia-reperfusion injury, nitric oxide, nebulization, cold ischemia, cyclic GMP, nitrotyrosine, oxidative stress, macrophage infiltration, interleukin-6, inducible nitric oxide synthase, dose-response relationship
- MeSH terms
- Animals, Lung, Male, Nebulizers and Vaporizers, Sodium Nitrite, Reperfusion Injury, Lung Transplantation, Rats, Sprague-Dawley, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
