Role of pH in protection by low sodium against hypoxic injury in isolated perfused rat livers

• Published in: Journal of hepatology 2006-05, Vol.44 (5), p.894-901
• Main Authors: Vairetti, Mariapia, Richelmi, Plinio, Bertè, Francantonio, Currin, Robert T., Lemasters, John J., Imberti, Roberto
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antiparasitic agents; BCECF; Biological and medical sciences; Cell Survival; Confocal microscopy; Diuretics, Osmotic - pharmacology; Edema - pathology; Edema - prevention & control; Gastroenterology. Liver. Pancreas. Abdomen; Glucose - pharmacology; Hepatocytes; Hepatocytes - pathology; Hydrogen-Ion Concentration - drug effects; Hypoxia - pathology; In Vitro Techniques; Ionophores - pharmacology; Lactate dehydrogenase; Liver - pathology; Male; Mannitol; Mannitol - pharmacology; Medical sciences; Monensin; Monensin - pharmacology; Organ Preservation - methods; Organ Preservation Solutions - pharmacology; Organ Size - drug effects; Osmotic stress; Perfusion; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Rats, Wistar; Sinusoidal cells; Sodium - pharmacology; Sucrose - pharmacology; Tromethamine - pharmacology
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2005.08.007

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. 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. 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.