Effects of fructose-1,6-diphosphate on endo- and myocardial purine metabolism during coronary artery bypass grafting surgery

J. Gál, B. Riedel, M. Kertai, G. Jancso, G. Acsády, D. Royston, E. Rőth

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aim. 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 (1.4g/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. Conclusion. 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.

Original languageEnglish
Pages (from-to)751-756
Number of pages6
JournalJournal of Cardiovascular Surgery
Volume48
Issue number6
Publication statusPublished - Dec 2007

Fingerprint

Coronary Artery Bypass
Inosine
Nucleotides
Cardiopulmonary Bypass
Control Groups
Reperfusion
Lactic Acid
Adenosine Triphosphate
Cardioplegic Solutions
purine
fructose-1,6-diphosphate
Glucose
Phosphofructokinases
Sinus of Valsalva
Hypoxanthine
Cytoprotection
Coronary Sinus
Glycolysis
Chromatography
Ischemia

Keywords

  • Cardiac surgical procedures
  • Coronary artery bypass grafting
  • Fructose 1,6-diphosphate
  • Heart
  • Reperfusion injury

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effects of fructose-1,6-diphosphate on endo- and myocardial purine metabolism during coronary artery bypass grafting surgery. / Gál, J.; Riedel, B.; Kertai, M.; Jancso, G.; Acsády, G.; Royston, D.; Rőth, E.

In: Journal of Cardiovascular Surgery, Vol. 48, No. 6, 12.2007, p. 751-756.

Research output: Contribution to journalArticle

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abstract = "Aim. 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 (1.4g/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. Conclusion. 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.",
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T1 - Effects of fructose-1,6-diphosphate on endo- and myocardial purine metabolism during coronary artery bypass grafting surgery

AU - Gál, J.

AU - Riedel, B.

AU - Kertai, M.

AU - Jancso, G.

AU - Acsády, G.

AU - Royston, D.

AU - Rőth, E.

PY - 2007/12

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N2 - Aim. 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 (1.4g/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. Conclusion. 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.

AB - Aim. 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 (1.4g/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. Conclusion. 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.

KW - Cardiac surgical procedures

KW - Coronary artery bypass grafting

KW - Fructose 1,6-diphosphate

KW - Heart

KW - Reperfusion injury

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