Integrity of perfused rat liver at different heat loads.
Isolated rat livers were perfused for 90 minutes at temperatures from 37 degrees to 43 degrees C. to evaluate the effects of heat alone on bile production, alanine aminotransferase, and asparate aminotransferase release, and light and electron microscopic structure. Bile production reached a plateau after 45 minutes at 43 degrees C. and after 60 minutes at 42 degrees C. At temperatures between 39 degrees and 41 degrees C., bile production was not significantly different from that produced at 37 degrees C. The timing and levels of alanine aminotransferase and aspartate aminotransferase released into the perfusates were similar, with increases after 45 minutes at 43 degrees C., after 60 minutes at 41 degrees and 42 degrees C. and after 75 minutes at 39 degrees and 40 degrees C. At the end of the 90-minute perfusion, light microscopy indicated vacuolization and severe dissociation of hepatocytes at 42 degrees and 43 degrees C., and pronounced centrilobular vacuolization at 41 degrees C. Electron microscopy demonstrated that hepatocytes had sustained extensive damage at 41 degrees to 43 degrees C. Mild focal and probably reversible damage occurred at 39 degrees and 40 degrees C. Since pH and O2 levels were regulated in a nonrecirculating system and perfusion rates were constant, neither acidosis, hypoxia, nor circulatory inadequacy were responsible for the alterations. Therefore, changes were attributed to the direct effects of heat, reflected a continuum from no detectable damage at 37 degrees C. to occasional necrosis of individual cells at 39 degrees to 40 degrees C. and culminated in widespread necrosis at 41 degrees to 43 degrees C. with a 90-minute exposure. These results reflect a time/temperature relationship over a range of temperatures. A hypothesis for the sequence of events in the pathogenesis of heat-induced hepatic injury is described.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000378:metabolism; D006358:Hot Temperature; D008099:Liver / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D008930:Mitochondria, Liver / Q000648:ultrastructure; D051381:Rats; D014617:Vacuoles / Q000648:ultrastructure
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase