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 in creased fatty acid oxidation, reduced pyruvate oxidation, and reduced pyruvate dehydrogenase (PDH) activity, leading to a decrease in cardia c 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 th e PDH complex (PDC) during reperfusion in severely ischemic hearts. Ma terials and methods. Seven-day old isolated working rabbit hearts (IE = 12) were perfused with modified Krebs solution containing 0.4 mM pal mitate, Pyruvate (5 mM) was added for a 10-min period either before or after a 30-min period of normothermic global ischemia. Cardiac functi onal indices before global ischemia and during reperfusion were correl ated with active and total PDC activity measured in 28 additional hear ts frozen at the various time points throughout the perfusion protocol . Results. Addition of pyruvate before ischemia increased the proporti on of active PDC but did not affect any measured functional indices. D uring early reperfusion, aortic how, cardiac output, and cardiac work were all significantly depressed compared to preischemic values. Addit ion of pyruvate significantly increased the proportion of active PDC a nd was also associated with a significant increase in aortic flow, car diac work, and developed pressure. Removal of pyruvate from the perfus ate resulted in a subsequent significant decrease in PDC activity and these functional parameters. Conclusion. During reperfusion of neonata l rabbit hearts, addition of pyruvate improves cardiac performance in association with activation of PDC. (C) 1998 Academic Press.