[Induced metabolic alterations due to experimental normothermic hepatic ischemia and the hepatoprotector effect of cyclosporin].
BACKGROUND
Hepatic transplantation is inevitably associated with periods of complete ischemia. However, the clamping of hepatic vascular pedicle is limited by the consequences of the post-ischemic injury to the liver.


OBJECTIVE
To determine the main metabolic alterations caused for the hepatic ischemia and the probable hepatoprotective effect cyclosporin.


METHODS
Normothermic hepatic ischemia during 60 minutes was induced in the rats. The time-course (0, 1, 6, 24 hours) of changes in blood and in the hepatic concentrations of lactate, pyruvate, glucose, ketone bodies and in the ratio of acetoacetate/3-hydroxybutyrate, as well as the cytoplasmic and mitochondrial redox state of the liver cells were determined. A group of animals was daily pre-treated with cyclosporine (10 mg/kg) during 4 days until the induction of hepatic ischemia, then they studied 1 hour after hepatic revascularization. Hepatic ischemia caused elevation in the concentrations of lactate in the liver, suggesting that a pronounced level of anaerobic metabolism occurred during the ischemia period. Liver ischemia promoted yet a fall in the concentration and in the ratio of ketone bodies (acetoacetate/3-hydroxybutyrate) in the arterial blood in the studied period of one hour post-revascularization, perhaps reflecting impairment of ketogenesis as a result of the ischemic injury.


CONCLUSIONS
The treatment with cyclosporine cause elevation in the concentration of ketone bodies and in the ratio of acetoacetate/3-hydroxybutyrate in the arterial blood 1 hour after reperfusion of the liver, suggesting that these drugs may accelerate the recovery of the ischemic hepatic lesion with reactivation of ketogenesis.
Garcia
José Huygens Parente
JH
Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE. huygens@secrel.com.br
Coelho
Gustavo Rego
GR
Sousa
Ivian Teixeira de
IT
Siqueira
Rafael Pontes de
RP
Vasconcelos
Paulo Roberto Leitão de
PR
D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000090:Acetoacetates / Q000378:metabolism; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D006498:Hepatectomy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007511:Ischemia / Q000378:metabolism*; D007657:Ketone Bodies / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000090:Acetoacetates; D007166:Immunosuppressive Agents; D007657:Ketone Bodies; D019344:Lactic Acid; C016635:acetoacetic acid; D016572:Cyclosporine; D020155:3-Hydroxybutyric Acid