Fructose-1,6-bisphosphate reduces myocardial injury in patients undergoing heart valve surgery

Abstract

OBJECTIVE: Fructose-1,6-diphosphate (FDP), an intermediary glycolytic pathway metabolite, has been shown to confer cardioprotection in patients undergoing cardiopulmonary bypass (CPB) through increasing levels of high energy phosphate (1). We evaluated the ultra-structural properties in addition to the clinical cardioprotective effects of FDP preconditioning in patients undergoing heart valve replacement surgery. METHODS: Sixty patients scheduled for heart valve replacement surgery were randomly assigned to FDP treatment and placebo groups (n=30 each). After anesthesia induction with etomidate and fentanyl, anesthesia was maintained with fentanyl and propofol at 60 -100 mg/kg/min supplemented with isoflurane at inspired concentration 0.75% - 1% in both groups. Patients in the FDP group were treated with FDP at 150 mg/kg administrated intravenously 20 min before initiation of CPB and 2.5 mM FDP as a cardioplegic additive. Patients in the placebo group received the same volume of normal saline infusion before CPB. Atrial appendage was harvested before CPB and during removal of the venous cannula for electron microscopy. Data are expressed in mean +/- standard derivation. Between-groups and within-group differences of bio-assay data were analyzed using two-way analysis of variance with repeated measures and Bonferroni corrections. RESULTS: Patients were similar in terms of demographics, preoperative left ventricular ejection fraction and aortic cross-clamping time (45.2 +/- 7.9 vs. 44.4 +/- 8.3 min). The number of patients requiring defibrillation to restore rhythm for separation from bypass was lower in the FDP group (7/30) than in the placebo group (18/30) (P<0.05). Plasma levels of cardiac specific troponin I (cTnI) and creatine kinase MB (CKMB) all increased significantly after aortic declamping relative to baseline (P<0.01), and peaked at 6 hour after CPB in both groups. The levels of cTnI and CKMB in the FDP group were lower at 30 min, 6 and 24 hours after CPB (all P<0.05) confirming the cardioprotective effect of FDP. Electron microscopy revealed extensive alteration in cristae architecture in the placebo mitochondria, including swelling and disruption of the inner mitochondrial membranes that was prevented by FDP treatment. FDP also had an inotrope sparing effect compared to placebo, but the duration of intensive care unit stay did not significantly differ between groups. CONCLUSION: It is concluded that FDP preconditioning can attenuate myocardial cellular injury and preserve cardiac mitochondrial integrity in patients undergoing heart valve replacement surgery using cardiopulmonary bypass.