Fructose 1,6-diphosphate administration attenuates post-ischemic ventricular dysfunction.
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, 250-300 g, underwent 30 min occlusion of the left anterior descending coronary artery followed by 30 min reperfusion. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of FDP or saline control. After 30 min reperfusion, myocardial function was evaluated with a left ventricular intracavitary pressure/volume conductance microcatheter. For bioenergetics studies, myocardium was isolated at 5 min 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+/-5.4 mmHg versus 69.1+/-1.9 mmHg; p<0.0005), dP/dt (5296+/-531 mmHg/s versus 2940+/-175 mmHg/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+/-5.0 mW/microL(2) versus 44.4+/-4.6 mW/microL(2); p<0.0477). Additionally, significantly enhanced ATP levels were observed in FDP animals (n=5) compared to controls (n=5) (535+/-156 nmol/g ischemic tissue versus 160+/-9.0 nmol/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.
University of Pennsylvania, School of Medicine, Department of Surgery, Philadelphia, PA 19104, USA.
Jeffrey E
JE
Cohen
Pavan
P
Atluri
Matthew D
MD
Taylor
Todd J
TJ
Grand
George P
GP
Liao
Corinna M
CM
Panlilio
Erik E
EE
Suarez
Suzanne E
SE
Zentko
Vivian M
VM
Hsu
Mark F
MF
Berry
Maximillian J
MJ
Smith
Timothy J
TJ
Gardner
H Lee
HL
Sweeney
Y Joseph
YJ
Woo
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000378:metabolism; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000378:metabolism; D005635:Fructosediphosphates / Q000008:administration & dosage* / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000150:complications / Q000201:enzymology*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D010732:Phosphofructokinase-1 / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology
D000889:Anti-Arrhythmia Agents; D002317:Cardiovascular Agents; D005635:Fructosediphosphates; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1; C068652:1-phosphofructokinase; C029063:fructose-1,6-diphosphate