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Related Experiment Videos

Decrease of ischemic injury to the isolated perfused rat liver by loop diuretics

R J Fiegen1, U Rauen, M Hartmann

  • 1Institut für Physiologische Chemie, Universitätsklinikum, Essen, Germany.

Hepatology (Baltimore, Md.)
|June 1, 1997
PubMed
Summary
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Loop diuretics furosemide and bumetanide protect against ischemic liver injury by inhibiting sodium accumulation via the Na+-K+-2Cl- cotransporter. This reduces liver damage and improves bile flow during reperfusion after ischemia.

Area of Science:

  • Hepatology
  • Ischemic Injury Research
  • Molecular Physiology

Background:

  • Sodium accumulation is implicated in the pathogenesis of ischemic liver injury.
  • Sodium-free media demonstrate protective effects on hepatocytes against hypoxic injury.
  • Challenges exist in perfusing isolated rat livers with sodium-free solutions due to vasoconstriction.

Purpose of the Study:

  • To investigate the protective effects of Na+-K+-2Cl- cotransporter inhibitors, furosemide and bumetanide, on ischemic liver injury.
  • To determine if blocking the Na+-K+-2Cl- cotransporter mitigates sodium influx during liver ischemia.
  • To assess the impact of these inhibitors on liver function markers and bile flow post-ischemia.

Main Methods:

  • Utilized an isolated rat liver model subjected to 60 minutes of warm ischemia at 37°C.

Related Experiment Videos

  • Administered furosemide and bumetanide as pretreatment before the ischemic period.
  • Measured lactate dehydrogenase (LDH) efflux as an indicator of liver injury.
  • Assessed intracellular sodium levels using 23Na-NMR spectroscopy.
  • Monitored bile flow during the reperfusion phase.

    • Main Results:

    • Pretreatment with furosemide and bumetanide significantly reduced LDH efflux post-ischemia compared to controls (P < .01).
    • Bile flow in the postischemic phase was improved by both furosemide and bumetanide treatment.
    • Bumetanide application attenuated the increase in intracellular sodium during ischemia (P < .05).
    • Extended ischemia (120 minutes) with bumetanide pretreatment also decreased LDH and aspartate aminotransferase release and increased bile flow.

    Conclusions:

    • Furosemide and bumetanide exhibit significant protective effects against rat liver warm ischemia.
    • The Na+-K+-2Cl- cotransporter appears to be a key pathway for sodium accumulation during liver ischemia.
    • Inhibiting this cotransporter offers a potential therapeutic strategy for mitigating ischemic liver injury.