Myocardial Protection Using Fructose-1,6-Diphosphate during Coronary Artery Bypass Graft Surgery: A Randomized, Placebo-Controlled Clinical Trial

Bernhard J. Riedel, J. Gál, Gillian Ellis, Paul J. Marangos, Anthony W. Fox, David Royston

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

In vitro and in vivo studies suggest that fructose-1,6-diphosphate (FDP), an intermediary glycolytic pathway metabolite, ameliorates ischemic tissue injury through increased high-energy phosphate levels and may therefore have cardioprotective properties in patients undergoing coronary artery bypass graft (CABG) surgery. We designed a randomized, placebo-controlled, double-blinded, sequential-cohort, dose-ranging safety study to test 5 FDP dosage regimens in patients (n = 120; 60 FDP, 60 control) undergoing CABG surgery. Of these dosage regimens, 3 produced no benefit, 1 produced improved cardiac function, and 1 required adjustment as a result of metabolic acidosis. This suggests that we achieved the intended effect of a dose-ranging study. The expected response was observed in patients treated with 250 mg/kg FDP IV before surgery and 2.5 mM FDP as a cardioplegic additive (n = 15). These patients had lower serum creatine kinase-MB levels 2, 4, and 6 h after reperfusion (P <0.05), fewer perioperative myocardial infarctions (P <0.05), and improved postoperative cardiac function, as evidenced by higher left ventricular stroke work index (LVSWI) 6, 12, and 16 h (P <0.01) and cardiac index (CI) at 12 and 16 h (P <0.05) after reperfusion. Overall efficacy of FDP was tested across all regimens that included IV FDP (n = 88; 44 FDP, 44 control) using 2 (FDP versus placebo) X 3 (dose size) factorial analyses. Area-under-curve (AUC) analysis demonstrated a significant increase in CI (AUC-16h, P = 0.013) and LVSWI (AUC-16h, P = 0.003) and reduction in CK-MB levels (AUC-16h, P <0.05) in FDP-treated patients. The internal consistency of this dataset suggests that FDP may provide myocardial protection in CABG surgery and supports previous laboratory and clinical studies of FDP in ischemic heart disease.

Original languageEnglish
Pages (from-to)20-29
Number of pages10
JournalAnesthesia and Analgesia
Volume98
Issue number1
Publication statusPublished - Jan 2004

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Coronary Artery Bypass
Randomized Controlled Trials
Placebos
Transplants
Area Under Curve
Reperfusion
fructose-1,6-diphosphate
Stroke
Creatine Kinase
Acidosis
Myocardial Ischemia
Phosphates
Myocardial Infarction
Safety

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Myocardial Protection Using Fructose-1,6-Diphosphate during Coronary Artery Bypass Graft Surgery : A Randomized, Placebo-Controlled Clinical Trial. / Riedel, Bernhard J.; Gál, J.; Ellis, Gillian; Marangos, Paul J.; Fox, Anthony W.; Royston, David.

In: Anesthesia and Analgesia, Vol. 98, No. 1, 01.2004, p. 20-29.

Research output: Contribution to journalArticle

Riedel, Bernhard J. ; Gál, J. ; Ellis, Gillian ; Marangos, Paul J. ; Fox, Anthony W. ; Royston, David. / Myocardial Protection Using Fructose-1,6-Diphosphate during Coronary Artery Bypass Graft Surgery : A Randomized, Placebo-Controlled Clinical Trial. In: Anesthesia and Analgesia. 2004 ; Vol. 98, No. 1. pp. 20-29.
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