Increasing survival of dogs subjected to hemorrhagic shock by administration of fructose 1-6 diphosphate.
Previous reports from this laboratory described animal experiments in which intravenous administration of fructose 1-6 diphosphate (FDP) at the onset of hypovolemia, toxemia, and trauma effected improvement in hemodynamic and metabolic parameters, attenuation of tissue damage, and a significant increase in survival. The obvious question remained: Would this agent be as effective if administered after the onset of the shock syndrome? Thus 72 anesthetized dogs were subjected to normotensive hemorrhagic shock and were subsequently treated with FDP at 30 minutes, 1 hour, 90 minutes, and 2 hours after exsanguination. Analysis of the results (as compared with vehicle-treated controls) revealed evidence of improved cardiac output and arterial pressure (p less than 0.02), conservation of effective circulatory volume, better oxygen utilization, and a significant increase in survival (p less than 0.0001). These results, in conjunction with earlier experimental and recent clinical data, indicate that the therapeutic effect of FDP in ischemic and hypoperfusion states is in part metabolically mediated by the augmentation of carbohydrate utilization. Prevention of tissue injury is in part due to the inhibition of generation of oxygen-derived free radicals by neutrophils.
D000818:Animals; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D005635:Fructosediphosphates / Q000378:metabolism / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006598:Hexosediphosphates / Q000627:therapeutic use*; D010732:Phosphofructokinase-1 / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism
D005635:Fructosediphosphates; D006598:Hexosediphosphates; D010732:Phosphofructokinase-1; C029063:fructose-1,6-diphosphate