Absence of renal hypoxia in the subacute phase of severe renal ischemia-reperfusion injury

Connie P.C. Ow, Jennifer P. Ngo, Md Mahbub Ullah, Giannie Barsha, Ruth C. Meex, Matthew J. Watt, Lucinda M. Hilliard, Maarten P. Koeners, Roger G. Evans

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12 Citations (Scopus)


Tissue hypoxia has been proposed as an important event in renal ischemia-reperfusion injury (IRI), particularly during the period of ischemia and in the immediate hours following reperfusion. However, little is known about renal oxygenation during the subacute phase of IRI. We employed four different methods to assess the temporal and spatial changes in tissue oxygenation during the subacute phase (24 h and 5 days after reperfusion) of a severe form of renal IRI in rats. We hypothesized that the kidney is hypoxic 24 h and 5 days after an hour of bilateral renal ischemia, driven by a disturbed balance(V between renal oxygen delivery (DO2) and oxygen consumption (VO2). Renal DO2 was not significantly reduced in the subacute phase of IRI. In contrast, renal VO2 was 55% less 24 h after reperfusion and 49% less 5 days after reperfusion than after sham ischemia. Inner medullary tissue PO2, measured by radiotelemetry, was 25 ± 12% (mean ± SE) greater 24 h after ischemia than after sham ischemia. By 5 days after reperfusion, tissue PO2 was similar to that in rats subjected to sham ischemia. Tissue PO2 measured by Clark electrode was consistently greater 24 h, but not 5 days, after ischemia than after sham ischemia. Cellular hypoxia, assessed by pimonidazole adduct immunohistochemistry, was largely absent at both time points, and tissue levels of hypoxia-inducible factors were downregulated following renal ischemia. Thus, in this model of severe IRI, tissue hypoxia does not appear to be an obligatory event during the subacute phase, likely because of the markedly reduced oxygen consumption.

Original languageEnglish
Pages (from-to)F1358-F1369
Number of pages12
JournalAmerican Journal of Physiology-Renal Physiology
Issue number5
Publication statusPublished - Nov 2018


  • Acute kidney injury
  • Hypoxia
  • Ischemia-reperfusion
  • Kidney
  • Oxygen

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