Fructose 1,6-Diphosphate Administration Attenuates Post-Ischemic Ventricular Dysfunction - 16/08/11
Corresponding author. Division of Cardiothoracic Surgery, 3400 Spruce Street, 6 Silverstein, Philadelphia, PA 19104, United States. Tel.: +1 215 662 2956; fax: +1 215 349 5798.Résumé |
Background |
Cardiomyocyte energy production during ischemia depends upon anaerobic glycolysis inefficiently yielding two ATP per glucose. Substrate augmentation with fructose 1,6-diphosphate (FDP) bypasses the ATP consuming steps of glucokinase and phosphofructokinase thus yielding four ATP per FDP. This study evaluated the impact of FDP administration on myocardial function after acute ischemia.
Methods |
Male Wistar rats, 250–300g, underwent 30min occlusion of the left anterior descending coronary artery followed by 30min reperfusion. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of FDP or saline control. After 30min reperfusion, myocardial function was evaluated with a left ventricular intracavitary pressure/volume conductance microcatheter. For bioenergetics studies, myocardium was isolated at 5min of ischemia and assayed for ATP levels.
Results |
Compared to controls (n=8), FDP animals (n=8) demonstrated significantly improved maximal left ventricular pressure (100.5±5.4mmHg versus 69.1±1.9mmHg; p<0.0005), dP/dt (5296±531mmHg/s versus 2940±175mmHg/s; p<0.0028), ejection fraction (29.1±1.7% versus 20.4±1.4%; p<0.0017), and preload adjusted maximal power (59.3±5.0mW/μL2 versus 44.4±4.6mW/μL2; p<0.0477). Additionally, significantly enhanced ATP levels were observed in FDP animals (n=5) compared to controls (n=5) (535±156nmol/g ischemic tissue versus 160±9.0nmol/g ischemic tissue; p<0.0369).
Conclusions |
The administration of the glycolytic intermediate, FDP, by intravenous injection, resulted in significantly improved myocardial function after ischemia and improved bioenergetics during ischemia.
Le texte complet de cet article est disponible en PDF.Keywords : Fructose 1,6-diphosphate, Myocardial ischemia, Glycolysis, ATP, Ventricular function
Plan
Vol 15 - N° 2
P. 119-123 - avril 2006 Retour au numéro
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