Fructose 1,6-Diphosphate Administration Attenuates Post-Ischemic Ventricular Dysfunction

Cohen, Jeffrey E.; Atluri, Pavan; Taylor, Matthew D.; Grand, Todd J.; Liao, George P.; Panlilio, Corinna M.; Suarez, Erik E.; Zentko, Suzanne E.; Hsu, Vivian M.; Berry, Mark F.; Smith, Maximillian J.; Gardner, Timothy J.; Sweeney, H. Lee; Woo, Y. Joseph

doi:10.1016/j.hlc.2005.12.004

« Previous Next »Heart, Lung and Circulation
Volume 15, Issue 2 , Pages 119-123, April 2006

Fructose 1,6-Diphosphate Administration Attenuates Post-Ischemic Ventricular Dysfunction

Jeffrey E. Cohen, BA
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Pavan Atluri, MD
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Matthew D. Taylor, BS
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Todd J. Grand, BS
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
George P. Liao, BS
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Corinna M. Panlilio, BA
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Erik E. Suarez, MD
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Suzanne E. Zentko, MD
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Vivian M. Hsu, BA
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Mark F. Berry, MD
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Maximillian J. Smith
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
Timothy J. Gardner, MD
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
H. Lee Sweeney, PhD
- University of Pennsylvania, School of Medicine, Department of Physiology, Philadelphia, PA, United States
Y. Joseph Woo, MD
- University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA, United States
- 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.

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.

Keywords: Fructose 1,6-diphosphate, Myocardial ischemia, Glycolysis, ATP, Ventricular function