Protection by acidotic pH against anoxic cell killing in perfused rat liver: evidence for a pH paradox.
Reperfusion of ischemic tissues causes a paradoxical injury. Here, we measured lactate dehydrogenase (LDH) release as an indicator of tissue damage in perfused rat livers during anoxia and reoxygenation. During anoxia, LDH release was substantially reduced at acidotic pH (pH 6.1-6.9). Using anoxia at pH 6.1 followed by reoxygenation at pH 7.3 to model ischemia and reperfusion, an abrupt release of LDH occurred after reperfusion. A similar release of LDH occurred when pH of anoxic livers was increased to 7.3 without reoxygenation but LDH release did not occur after reoxygenation at pH 6.1. Thus, a rapid increase of pH rather than reoxygenation accounted for tissue injury after reperfusion of ischemic liver.
Currin
R T
RT
Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599.
Gores
G J
GJ
Thurman
R G
RG
Lemasters
J J
JJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival; D003676:Deferoxamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000503:physiopathology*
D000975:Antioxidants; D007770:L-Lactate Dehydrogenase; D003676:Deferoxamine