DECREASE OF ISCHEMIC-INJURY TO THE ISOLATED-PERFUSED RAT-LIVER BY LOOP DIURETICS

Recent studies suggest a major role played by sodium in the pathogenes is of ischemic liver injury: in these studies, sodium-free media have been shown to offer protection against hypoxic injury to isolated hepa tocytes. As sodium-free perfusions of the isolated rat liver proved im possible because of extensive vasoconstriction, we assessed the effect s of two inhibitors of the Na+-K+-2Cl(-) cotransporter, the loop diure tics furosemide and bumetanide, on ischemic liver injury. In untreated control Livers lactate dehydrogenase (LDH) efflux immediately after r eperfusion after 60 minutes of ischemia at 37 degrees C was 1666 +/- 4 73 U/L/ When livers were pretreated with furosemide or bumetanide befo re the ischemic period, LDH efflux was only 773 +/- 292 U/L and 702 +/ - 183 U/L respectively (P < .01). LDH activity in the effluent of the pretreated livers remained significantly below the values of ischemic control livers for the whole reperfusion period of 90 minutes. Bile no w in the postischemic phase was improved by pretreatment with furosemi de or bumetanide. The increase in intracellular sodium, as measured by Na-23-NMR, was attenuated from 193% +/- 71% during 60 minutes of isch emia in controls to 148% +/- 80% after bumetanide application (P < .05 ). Also, after 120 minutes of warm ischemia, LDH and aspartate aminotr ansferase release were significantly decreased and bile flow increased by pretreatment with bumetanide. Thus, both furosemide and bumetanide showed a clear benificial effect on rat livers subjected to warm isch emia. These data suggest that one means by which sodium ions are accum ulated during liver ischemia might be the Na+-K+-2Cl(-) cotransporter, which is blocked by furosemide and bumetanide.