Hemodynamics and metabolic effects of fructose 1-6 diphosphate in ischemia and shock--experimental and clinical observations.
Numerous interventions have been used to protect organ systems and cellular viability from the lethal injury accompanying hypoperfusion and ischemia. Some measures have been directed toward improving perfusion, while others have attempted to enhance the metabolic processes. Our work has focused for the most part on augmenting the anaerobic carbohydrate utilization in ischemic and hypoperfused tissues with fructose-1,6-diphosphate (FDP). Such an approach is based on the premise that exogenous FDP will restore the activity of glycolysis, which has been inhibited by acidosis, by intervening in the Embden-Meyerhoff pathway both as a metabolic regulator and as a high-energy substrate. We have tested this hypothesis in more than 1,000 animals subjected to shock or regional ischemia, and the results appear to confirm our presumption. In myocardial infarction, FDP improves hemodynamic parameters, attenuates ECG-proven ischemic injury and dysrhythmias, prevents ATP and creatine phosphate depletion from ischemic myocardium, reduces infarct size, and increases survival. In hemorrhagic, traumatic, and endotoxin shock, FDP improves hemodynamics, attenuates organ injury, and increases survival. Recently we demonstrated that FDP attenuates the reperfusion ischemic tissue injury by inhibiting the generation of oxygen free radicals by neutrophils. In normal volunteers, this agent increases carbohydrate utilization, while administration of a like amount of glucose produces no effect. In patients with myocardial infarction, FDP appears to have the same effect as that observed in the animal model. When this agent is administered to patients in traumatic, hemorrhagic, or septic shock, hemodynamic and pulmonary function are significantly improved. In patients with adult respiratory distress syndrome, similar beneficial effects have been observed with FDP administration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy; D004285:Dogs; D005260:Female; D005635:Fructosediphosphates / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects*; D006598:Hexosediphosphates / Q000627:therapeutic use*; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012128:Respiratory Distress Syndrome / Q000188:drug therapy; D012769:Shock / Q000188:drug therapy* / Q000378:metabolism
D005635:Fructosediphosphates; D006598:Hexosediphosphates; C029063:fructose-1,6-diphosphate