The purpose of the present study was to characterize the role of Na+, pH and cellular swelling in the pathogenesis of hypoxic injury to rat livers. METHODS AND RESULTS: When livers were perfused with hypoxic Krebs-Henseleit bicarbonate buffer (KHB) containing 143 mM Na+, release of LDH began after 30 min and was maximal after 60 min. In livers perfused with choline-substituted low-Na+ KHB (25 mM Na+), LDH release began after 60 min and peaked after 120 min or longer. Supplementation of KHB with mannitol, a permeant sugar with antioxidant properties, suppressed LDH release, whereas sucrose, an impermeant disaccharide, did not afford protection. At the end of hypoxic perfusions with KHB and low-Na+ KHB, liver weight was not different, whereas mannitol but not sucrose increased liver weight after hypoxia. At pH 7.4, monensin, a Na+-H+ ionophore, reversed protection against hypoxia by low-Na+ KHB (10 mM Na+) but had no effect at pH 6.8. As measured directly by confocal microscopy of biscarboxyethylcarboxyfluorescein fluorescence, pH was lower during perfusion with low-Na+ KHB than KHB. CONCLUSIONS: Cytoprotection by low Na+ was not mediated by prevention of Na+-dependent tissue swelling. Rather, promotion of intracellular acidification likely mediates cytoprotection in low-Na+ buffer.
Role of pH in protection by low sodium against hypoxic injury in isolated perfused rat livers
VAIRETTI, MARIAPIA;RICHELMI, PLINIO;BERTE', FRANCANTONIO;
2006-01-01
Abstract
The purpose of the present study was to characterize the role of Na+, pH and cellular swelling in the pathogenesis of hypoxic injury to rat livers. METHODS AND RESULTS: When livers were perfused with hypoxic Krebs-Henseleit bicarbonate buffer (KHB) containing 143 mM Na+, release of LDH began after 30 min and was maximal after 60 min. In livers perfused with choline-substituted low-Na+ KHB (25 mM Na+), LDH release began after 60 min and peaked after 120 min or longer. Supplementation of KHB with mannitol, a permeant sugar with antioxidant properties, suppressed LDH release, whereas sucrose, an impermeant disaccharide, did not afford protection. At the end of hypoxic perfusions with KHB and low-Na+ KHB, liver weight was not different, whereas mannitol but not sucrose increased liver weight after hypoxia. At pH 7.4, monensin, a Na+-H+ ionophore, reversed protection against hypoxia by low-Na+ KHB (10 mM Na+) but had no effect at pH 6.8. As measured directly by confocal microscopy of biscarboxyethylcarboxyfluorescein fluorescence, pH was lower during perfusion with low-Na+ KHB than KHB. CONCLUSIONS: Cytoprotection by low Na+ was not mediated by prevention of Na+-dependent tissue swelling. Rather, promotion of intracellular acidification likely mediates cytoprotection in low-Na+ buffer.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
