{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T20:25:16Z","timestamp":1772655916632,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Renal arterial infusion of tempol (RAT) at the onset of Gram\u2010negative sepsis can prevent sepsis\u2010induced medullary tissue hypoxia and acute kidney injury (AKI). However, it is not known whether treatment with tempol at a clinically relevant time point of sepsis is similarly effective. Thus, we examined whether tempol can reverse renal medullary tissue hypoxia after ovine Gram\u2010negative septic AKI. Following right unilateral nephrectomy, the left kidney was instrumented with a renal arterial catheter and oxygen\u2010sensing fibre\u2010optic probes into the renal medulla. After 23\u00a0h of <jats:italic>Escherichia coli<\/jats:italic> infusion, conscious sheep were fluid resuscitated with Hartmann's solution (30\u00a0mL\/kg over 0.5\u00a0h) and randomized to intravenous tempol (IVT; <jats:italic>n<\/jats:italic>\u00a0=\u00a07) at 30\u00a0mg\/kg\/h, RAT (3\u00a0mg\/kg\/h; <jats:italic>n<\/jats:italic>\u00a0=\u00a06) or vehicle (<jats:italic>n<\/jats:italic>\u00a0=\u00a05) from 24 to 31\u00a0h of sepsis. At 31\u00a0h, <jats:italic>E. coli<\/jats:italic> infusion ceased, and sheep received ceftriaxone (1\u00a0g) and were allowed a 48\u00a0h recovery period. At 23\u00a0h of <jats:italic>E. coli<\/jats:italic> infusion, septic sheep developed a 2.2\u00a0\u00b1\u00a00.8\u2010fold increase in plasma creatinine and a 57%\u00a0\u00b1\u00a06% decrease in urine output, and the renal medulla was ischaemic and hypoxic. Neither RAT nor IVT attenuated the sepsis\u2010induced renal medullary tissue hypoxia during the 7\u00a0h intervention period. Renal medullary tissue partial pressure of O<jats:sub>2<\/jats:sub> returned to the pre\u2010morbid levels in all groups by 16\u00a0h after treatment cessation, and sepsis was resolved with antibiotics. In conclusion, in sheep with established septic AKI, treatment with RAT or IVT did not improve renal medullary oxygenation or kidney function, in contrast to the effectiveness we have shown in early sepsis. These findings emphasize the dramatically different response to a treatment in early compared with late stages of sepsis.<\/jats:p>","DOI":"10.1113\/ep092396","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T19:09:07Z","timestamp":1758568147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of tempol on renal medullary tissue hypoxia in an ovine model of Gram\u2010negative septic acute kidney injury"],"prefix":"10.1113","author":[{"given":"Rachel","family":"Peiris","sequence":"first","affiliation":[{"name":"Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-8905","authenticated-orcid":false,"given":"Anton","family":"Trask\u2010Marino","sequence":"additional","affiliation":[{"name":"Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alemayehu","family":"Jufar","sequence":"additional","affiliation":[{"name":"Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashenafi H.","family":"Betrie","sequence":"additional","affiliation":[{"name":"Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Southon","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Laboratory, Florey Institute of Neuroscience and Mental Health The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally G.","family":"Hood","sequence":"additional","affiliation":[{"name":"Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rinaldo","family":"Bellomo","sequence":"additional","affiliation":[{"name":"Department of Critical Care, Melbourne Medical School The University of Melbourne  Melbourne Victoria Australia"},{"name":"Australian and New Zealand Intensive Care Research Centre (ANZIC\u2010RC), School of Public Health and Preventive Medicine Monash University  Melbourne Victoria Australia"},{"name":"Department of Intensive Care Austin Hospital  Melbourne Victoria Australia"},{"name":"Department of Intensive Care Royal Melbourne Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham H.","family":"Hulst","sequence":"additional","affiliation":[{"name":"Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health The University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Anesthesiology, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clive N.","family":"May","sequence":"additional","affiliation":[{"name":"Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health The University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Critical Care, Melbourne Medical School The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5402-1809","authenticated-orcid":false,"given":"Connie P. 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