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


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.
Vairetti
Mariapia
M
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Richelmi
Plinio
P
Bertè
Francantonio
F
Currin
Robert T
RT
Lemasters
John J
JJ
Imberti
Roberto
R
D000818:Animals; D002470:Cell Survival; D004234:Diuretics, Osmotic / Q000494:pharmacology; D004487:Edema / Q000473:pathology / Q000517:prevention & control; D005947:Glucose / Q000494:pharmacology; D022781:Hepatocytes / Q000473:pathology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D000860:Hypoxia / Q000473:pathology*; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008099:Liver / Q000473:pathology*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology*; D013395:Sucrose / Q000494:pharmacology; D014325:Tromethamine / Q000494:pharmacology
D004234:Diuretics, Osmotic; D007476:Ionophores; C074097:Krebs-Henseleit solution; D019188:Organ Preservation Solutions; D014325:Tromethamine; D008353:Mannitol; D013395:Sucrose; D008985:Monensin; D012964:Sodium; D005947:Glucose