Pyruvate augments mechanical function via activation of the pyruvate dehydrogenase complex in reperfused ischemic immature rabbit hearts.
BACKGROUND
Reperfusion of ischemic adult hearts is associated with increased fatty acid oxidation, reduced pyruvate oxidation, and reduced pyruvate dehydrogenase (PDH) activity, leading to a decrease in cardiac efficiency. These effects may be amplified in newborn hearts because of the immaturity of their PDH pathway. We hypothesize that pyruvate can augment mechanical function in the immature heart by activating the PDH complex (PDC) during reperfusion in severely ischemic hearts.


METHODS
Seven-day old isolated working rabbit hearts (n = 12) were perfused with modified Krebs solution containing 0.4 mM palmitate. Pyruvate (5 mM) was added for a 10-min period either before or after a 30-min period of normothermic global ischemia. Cardiac functional indices before global ischemia and during reperfusion were correlated with active and total PDC activity measured in 28 additional hearts frozen at the various time points throughout the perfusion protocol.


RESULTS
Addition of pyruvate before ischemia increased the proportion of active PDC but did not affect any measured functional indices. During early reperfusion, aortic flow, cardiac output, and cardiac work were all significantly depressed compared to preischemic values. Addition of pyruvate significantly increased the proportion of active PDC and was also associated with a significant increase in aortic flow, cardiac work, and developed pressure. Removal of pyruvate from the perfusate resulted in a subsequent significant decrease in PDC activity and these functional parameters.


CONCLUSIONS
During reperfusion of neonatal rabbit hearts, addition of pyruvate improves cardiac performance in association with activation of PDC.
Saiki
Y
Y
Division of Cardiovascular Surgery, University of Alberta, Edmonton, Alberta, T6G 2B7, Canada.
Lopaschuk
G D
GD
Dodge
K
K
Yamaya
K
K
Morgan
C
C
Rebeyka
I M
IM
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D019289:Pyruvic Acid / Q000494:pharmacology*; D011817:Rabbits
D011768:Pyruvate Dehydrogenase Complex; D019289:Pyruvic Acid