Effects of fructose-1,6-diphosphate on endo- and myocardial purine metabolism during coronary artery bypass grafting surgery.
OBJECTIVE
During ischemia, the glycolytic pathway is up-regulated to anaerobically produce adenosine triphosphate (ATP). However, this is short-lived, due to negative feedback on phosphofructokinase from accumulating lactate. Since fructose-1,6-diphosphate (FDP) enters glycolysis distal to this inhibitory site, exogenously administered FDP may yield ATP-independent lactate accumulation and thus ameliorate ischemic injury. The aim of this prospective randomized study was to investigate whether the improved myocardial preservation by FDP could be attributed to improved intermediary metabolism in patients who underwent coronary artery bypass grafting surgery (CABG).


METHODS
Thirty-eight patients scheduled for elective CABG were studied. During operation, aortic and coronary sinus blood were collected at different timepoints and analysed by chromatography. Ten patients received 250 mg/kg FDP and 10 received 5% dextrose (control) as intravenous pretreatment prior to cardiopulmonary bypass. In the second stage, 9 patients received 2.5 mM (1.4 g/L) FDP and 9 patients 5% dextrose with the cardioplegic solution. Myocardial metabolism was quantified by measuring nucleotide catabolites including inosine and hypoxanthine.


RESULTS
The release of inosine-hypoxantine was increased in both the FDP and the control groups; however, compared to baseline, inosine-hypoxantine levels were significantly elevated at 0, 1, 5 and 10 minutes following reperfusion in the control group. This was in contrast to the earlier recovery to baseline levels (after 5 minutes following reperfusion) in the FDP group.


CONCLUSIONS
These data suggest that FDP may contribute to myocardial cytoprotection during cardiopulmonary bypass. Moreover, myocardial nucleotide metabolite levels showed no evidence for a protective effect of FDP on nucleotide degradation between the treated and the control groups.
Gal
J
J
Department of Anaesthesia, Royal Brompton and Harefield Hospital NHS Trust, London, UK. janos_gal@hotmail.com
Riedel
B
B
Kertai
M D
MD
Jancso
G
G
Acsady
G
G
Royston
D
D
Roth
E
E
D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005635:Fructosediphosphates / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D010919:Placebos; D011687:Purines / Q000378:metabolism*; D013997:Time Factors
D002317:Cardiovascular Agents; D005635:Fructosediphosphates; D010919:Placebos; D011687:Purines; C029063:fructose-1,6-diphosphate