The Use of Insulin and Glucose during Resuscitation from Hemorrhagic Shock Increases Hepatic ATP

• Published in: The Journal of surgical research 2000-08, Vol.92 (2), p.171-176
• Main Authors: Chang, Craig G., Van Way, Charles W., Dhar, Animesh, Helling, Thomas, Hahn, Yoav
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Monophosphate - metabolism; Adenosine Triphosphate - metabolism; ADP; AMP; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; ATP; Biological and medical sciences; Blood Glucose - metabolism; Blood Pressure; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care; glucose; Glucose - therapeutic use; hemorrhage; insulin; Insulin - therapeutic use; Intensive care medicine; Isotonic Solutions - administration & dosage; Isotonic Solutions - therapeutic use; Liver - drug effects; Liver - metabolism; Male; Medical sciences; metabolites; Nucleosides - metabolism; Potassium - blood; Rats; Rats, Sprague-Dawley; Resuscitation; shock; Shock, Hemorrhagic - metabolism; Shock, Hemorrhagic - physiopathology; Shock, Hemorrhagic - therapy; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.2000.5857

Background. Hemorrhagic shock produces a marked decrease in hepatic ATP, adenylate 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 work has shown that supraphysiologic doses of insulin have salutary effects in animals with hemorrhagic shock and in cardiac patients. It appears that insulin causes increased availability of glucose and energy-producing substrates. This study examined whether resuscitation with glucose and insulin after hemorrhagic shock would alter the changes previously seen to occur in hepatic ATP levels, adenylate energy charge, or nucleotide metabolites. Methods. Male Sprague–Dawley rats were bled to a mean arterial blood pressure 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 insulin. Liver biopsies were obtained prior to shock (baseline), after 30 min of shock (shock), and 90 min after resuscitation (90 min). Tissue levels of ATP, ADP, AMP, adenosine, inosine, hypoxanthine, and xanthine were measured. Serum at 90 min was evaluated for potassium, glucose, and tumor necrosis factor α (TNF-α). Results. The insulin-treated group had significantly increased hepatic ATP and energy charge following resuscitation compared with the other two groups. The insulin group also exhibited significant hypoglycemia. Total adenine nucleotides (ATP, ADP, and AMP) were significantly elevated 90 min postresuscitation in the insulin group. Mean blood pressures throughout the experiment were not significantly different among groups. TNF-α was highest in the insulin-treated group, but this was not significant. Conclusions. Resuscitation with insulin and dextrose significantly increased 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 significant effect on blood pressure or TNF-α. However, it caused significant hypoglycemia and hypokalemia.