ADMINISTRATION OF ATP-MGCL2 FOLLOWING HEMORRHAGE AND RESUSCITATION INCREASES HEPATIC PHOSPHOENOLPYRUVATE CARBOXYKINASE AND DECREASES PYRUVATE-KINASE ACTIVITIES

Since administration of ATP-MgCl2 following trauma and hemorrhagic sho ck improves tissue perfusion as well as cell and organ function, the a im of this study was to determine whether this agent has any salutary effects on the hepatic rate-controlling enzymes specific for gluconeog enesis, such as phosphoenolpyruvate carboxykinase (PEPCK), and for gly colysis, such as pyruvate kinase (PK), under such conditions. To study this, rats underwent a 5-cm midline laparotomy (i.e., trauma-induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum bleed out volume was returned in the form of R inger's lactate (RL). The animals were then resuscitated with 3 times the volume of shed blood with RL over 45 min, followed by 2 times RL w ith ATP-MgCl2 (50 mu mol/kg body wt.) or an equivalent volume of norma l saline over 95 min. Hepatic PEPCK, PK and glucokinase activities wer e determined 4 h after the completion of resuscitation. The mRNA level s of PEPCK and PK in the isolated hepatocytes were determined by North ern blot analysis. The results indicate that glucokinase activity was not significantly altered after hemorrhage, irrespective of ATP-MgCl2 treatment. Although the mRNA levels of PEPCK were similar in all group s, PEPCK activity decreased significantly after hemorrhage. ATP-MgCl2 treatment, however, restored PEPCK activity. Hemorrhage resulted in an increase in PK activity and its mRNA. ATP-MgCl2 treatment significant ly decreased PK activity and the mRNA. Thus, up-regulation of the gluc oneogenic enzyme, PEPCK, and down-regulation of the glycolytic enzyme, PK, by ATP-MgCl2 may be responsible, in part, for the beneficial effe cts of this agent following trauma-hemorrhage and resuscitation. (C) 1 997 Elsevier Science B.V.