Abstract
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 between renal oxygen delivery (Do2) and oxygen consumption (V̇o2). Renal Do2 was not significantly reduced in the subacute phase of IRI. In contrast, renal V̇o2 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.
Highlights
Acute kidney injury (AKI) is a major cause of death and disability globally and places a major acute burden on health care systems [26]
At 24 h after reperfusion, tissue PO2 tended to be greater in rats subjected to ischemia than in those subjected to sham ischemia, the difference reaching statistical significance at depths of 5 mm and 9 and 10 mm
Twenty-four hours after ischemia, mean Glomerular filtration rate (GFR) (Ϫ99%), urine flow (Ϫ82%), and sodium excretion (Ϫ85%) were less than in rats subjected to ischemia than in those subjected to sham ischemia (Table 2)
Summary
Acute kidney injury (AKI) is a major cause of death and disability globally and places a major acute burden on health care systems [26]. Ischemia-reperfusion injury (IRI) sustained from medical interventions often arises from the obligatory need to restrict or completely prevent blood flow to the kidney, resulting in a period of severe hypoxia or complete anoxia [15]. This information is required if we are to understand the role of tissue hypoxia in the natural history of AKI, either as it progresses to end-stage renal disease or as renal function recovers but the risk of later CKD is increased
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