Biochemical and morphologic effects after extended liver resection in rats: preliminary results.
After hepatic resection and transplantation with a partial graft, death and regeneration of the hepatocytes coexist in the liver. However, when the functional liver mass is inadequate to ensure a proper balance between regeneration vs functional and metabolic demands, small-for-size syndrome develops. We assessed the early effects of extended hepatic resection on liver function in a rat model. Six male Sprague-Dawley rats underwent 80% resection of the liver, and 6 rats served as a control group. At 6 hours after resection, blood samples were obtained from the hepatic vein for measurement of reduced glutathione (GSH), oxidized glutathione (GSSG), and hepatic venous oxygen saturation (Shvo(2)), and for standard liver function tests including determination of concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, and total bilirubin. The remnant lobe was removed for GSH assay and histopathologic analysis. In the resection group, values were significantly higher for ALT (P = .002), AST (P = .002), and Shvo(2) (P = .01), whereas a significant decrease was observed for blood GSH (P = .009) but not liver GSH. Also in the resection group, we observed characteristic hepatocyte vacuolization with a gradient from periportal acinar zone 1 to the centrolobular area, the presence of hemorrhagic necrosis, and several leukocyte adhesions. The Shvo(2) and GSH data suggest early alteration of oxygen metabolism, as demonstrated by the reduction in oxygen uptake and decreased liver GSH secretion, with preservation of hepatic GSH. Mitochondrial dysfunction and oxidative injury seem to have a crucial role in early onset of liver damage.
Di Domenico
S
S
Department of Transplantation, San Martino University Hospital, Genoa, Italy. didomenico.stefano@gmail.com
Santori
G
G
Balbis
E
E
Traverso
N
N
Gentile
R
R
Bocca
B
B
Gelli
M
M
Andorno
E
E
Cottalasso
D
D
Valente
U
U
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D018757:GABA Modulators / Q000494:pharmacology; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology; D008099:Liver / Q000033:anatomy & histology / Q000502:physiology; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000502:physiology*; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008930:Mitochondria, Liver / Q000473:pathology / Q000502:physiology; D009929:Organ Size; D011168:Portal System / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013992:Tiletamine / Q000494:pharmacology; D014682:Vena Cava, Inferior / Q000601:surgery; D015041:Zolazepam / Q000494:pharmacology
D000927:Anticonvulsants; D018757:GABA Modulators; D013992:Tiletamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D015041:Zolazepam