The use of insulin and glucose during resuscitation from hemorrhagic shockincreases hepatic ATP

Background. Hemorrhagic shock produces a marked decrease in hepatic ATP, ad enylate energy charge, and total adenosine nucleotides. This is followed by slow recovery to normal levels after resuscitation. Nucleotide metabolites are increased following shock and resuscitation. Previous experimental wor k has shown that supraphysiologic doses of insulin have salutary effects in animals with hemorrhagic shock and in cardiac patients. It appears that in sulin causes increased availability of glucose and energy-producing substra tes. This study examined whether resuscitation with glucose and insulin aft er hemorrhagic shock would alter the changes previously seen to occur in he patic ATP levels, adenylate energy charge, or nucleotide metabolites. Methods. Male Sprague-Dawley rats were bled to a mean arterial blood pressu re of 40 mm Hg for 30 min. They were then resuscitated with the shed blood and one of three fluids: (1) lactated Ringer's, (2) lactated Ringer's with 10% glucose, (3) lactated Ringer's with 10% glucose + 6 units/kg regular in sulin. Liver biopsies were obtained prior to shock (baseline), after 30 min of shock (shock), and 90 min after resuscitation (90 min). Tissue levels o f ATP, ADP, AMP, adenosine, inosine, hypoxanthine, and xanthine were measur ed. Serum at 90 min was evaluated for potassium, glucose, and tumor necrosi s factor alpha (TNF-alpha). Results. The insulin-treated group had significantly increased hepatic ATP and energy charge following resuscitation compared with the other two group s. The insulin group also exhibited significant hypoglycemia. Total adenine nucleotides (ATP, ADP, and AMP) were significantly elevated 90 min postres uscitation in the insulin group. Mean blood pressures throughout the experi ment were not significantly different among groups. TNF-alpha was highest i n the insulin-treated group, but this was not significant. Conclusions. Resuscitation with insulin and dextrose significantly increase d hepatic ATP and adenylate energy charge after hemorrhagic shock in rats. Total nucleotide pool levels were not different between groups, indicating that there was a shift of the equilibrium away from the metabolites toward ATP and ADP in the insulin-treated group. Insulin treatment had no signific ant effect on blood pressure or TNF-alpha. However, it caused significant h ypoglycemia and hypokalemia. (C) 2000 Academic Press.