Hypoxia-reoxygenation is as damaging as ischemia-reperfusion in the rat liver

Sidhartha Tan, Yoshifumi Yokoyama, Ziwei Wang, Fen Zhou, Vance Nielsen, Alan D. Murdoch, Craig Adams, Dale A. Parks

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Objective: We hypothasized that the extent of injury and release of xanthine oxidase, an oxidant generator, into the circulation would be less in normal-flow hypoxia-reoxygenation than in equal duration no-flow ischemia- reperfusion. Design: Randomized study. Setting: University-based animal research facility. Subjects: Male Sprague-Dawley rats. Interventions: The livers were isolated, perfused, and then randomly subjected to 2 hrs of hypoxia (normal flow, low oxygen) or ischemia (no flow, no oxygen), and 2 hrs of reperfusion. Hepatocytes were also isolated, and were subjected to either: a) hypoxia (0, 2, 4, and 6 hrs); or b) hypoxia (2 and 4 hrs) with reoxygenation (2 hrs). Measurements and Main Results: The extent of liver Injury (as assessed by release of hepetocellular enzymes) and the release of xanthine oxidase were measured from isolated-perfused rat livers and cultured hepatocytes. The pattern of release of xanthine oxidase in isolated-perfused liver effluent was different in hypoxiareoxygenation compared with ischemia- reperfusion. During hypoxia, xanthine oxidase ritually increased in the effluent; then, the xanthine oxidase decreased to low concentrations during reoxygenation. After ischemia, them was a sharp spike in xanthine oxidase at 1 min of reperfusion, with a rapid decrease to low concentrations. The total release of xanthine oxidase during hypoxia-reoxygenation was similar to that during ischemiareperfusion. Lactate dehydrogenase and other markers of liver Injury showed a pattern of release that was similar to that of xanthine oxidase, but the total release of markers was not different between the two groups. In hepatocytes, most of the release of enzymes occurred in hypoxia, and the rate of release was not different between hypoxia and hypoxia- reoxygenation. Conclusions: Hypoxia-reoxygenation results in as much damage to the liver as ischemia-reperfusion, and results in the release of a similar amount of oxidant-producing xanthine oxidase into the circulation.

Original languageEnglish (US)
Pages (from-to)1089-1095
Number of pages7
JournalCritical care medicine
Volume26
Issue number6
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Alanine aminotransferase
  • Aspartate aminotransferase
  • Blood circulation
  • Free radicals
  • Lactate dehydrogenase
  • Oxygen consumption
  • Xanthine oxidase

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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