Altered cellular calcium regulation and hepatic glucose production during hemorrhagic shock.
The relationship between intracellular Ca2+ and glucose production in the liver during early and late states of hemorrhagic shock was studied. Rats were anesthetized with intraperitoneal sodium pentobarbital and both femoral arteries and one femoral vein were cannulated. Rats were divided into two groups. One group was subjected to hemorrhagic shock by rapid withdrawal of blood to a mean arterial pressure of 40 mm Hg and maintained in shock for either 30 or 150 min. Rats in the control group were observed for the same time period. Hepatic glucose production was evaluated in both groups by a nonrecirculating liver perfusion model with and without lactate as a substrate. Intracellular free Ca2+ in hepatocytes was measured using the Ca2+ selective indicator Fura-2, under basal and epinephrine-stimulated conditions. Hyperglycemia and hyperlacticacidemia were observed in vivo at 30 min of hemorrhagic shock, whereas hypoglycemia and hyperlacticacidemia were observed at 150 min of shock. Hepatic glucose production in isolated perfused livers was significantly depressed at 30 min in animals subjected to shock (P less than 0.05). Lactate-induced glucose production was significantly attenuated at 30 and 150 min (P less than 0.05). Basal Ca2+, in isolated hepatocytes, at 30 and 150 min of hemorrhagic shock was significantly (P less than 0.05) higher than in controls. The hemorrhagic shock rat hepatocytes failed to evaluate intracellular free Ca2+ upon stimulation with 10(-5) M epinephrine. These results demonstrate that hemorrhagic shock is associated with an increase in hepatocyte intracellular Ca2+ concentration along with attenuation of hormone-mediated mobilization of calcium and substrate specific stimulation of hepatic glucose production.
Maitra
S R
SR
Department of Surgery, School of Medicine, State University of New York, Stony Brook 11794-8191.
Geller
E R
ER
Pan
W
W
Kennedy
P R
PR
Higgins
L D
LD
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D005947:Glucose / Q000096:biosynthesis*; D007700:Kinetics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism*
D001786:Blood Glucose; D005456:Fluorescent Dyes; D007773:Lactates; D019344:Lactic Acid; D005947:Glucose; D002118:Calcium; D016257:Fura-2; D004837:Epinephrine