Hepatic preconditioning preserves energy metabolism during sustained ischemia

We evaluated the possibility that ischemic preconditioning could modify hep atic energy metabolism during ischemia. Accordingly, high-energy nucleotide s and their degradation products, glycogen and glycolytic intermediates and regulatory metabolites, were compared between preconditioned and nonprecon ditioned livers. Preconditioning preserved to a greater extent ATP, adenine nucleotide pool, and adenylate energy charge; the accumulation of adenine nucleosides and bases was much lower in preconditioned livers, thus reflect ing slower adenine nucleotide degradation. These effects were associated wi th a decrease in glycogen depletion and reduced accumulation of hexose 6-ph osphates and lactate. 6-Phosphofructo-2-kinase decreased in both groups, re ducing the availability of fructose-2,6-bisphosphate. Preconditioning susta ined metabolite concentration at higher levels although this was not correl ated with an increased glycolytic rate, suggesting that adenine nucleotides and cAMP may play the main role in the modulation of glycolytic pathway. P reconditioning attenuated the rise in cAMP and limited the accumulation of hexose 6-phosphates and lactate, probably by reducing glycogen depletion. O ur results suggest the induction of metabolic arrest and/or associated meta bolic downregulation as energetic cost-saving mechanisms that could be indu ced by preconditioning.