TY - JOUR
T1 - Pyruvate augments mechanical function via activation of the pyruvate dehydrogenase complex in reperfused ischemic immature rabbit hearts
AU - Saiki, Yoshikatsu
AU - Lopaschuk, Gary D.
AU - Dodge, Karen
AU - Yamaya, Kazuhiro
AU - Morgan, Catherine
AU - Rebeyka, Ivan M.
N1 - Funding Information:
Presented at the Annual Meeting of the Association for Academic Surgery, Dallas, Texas, November 6–8, 1997. 1This work was supported by the Medical Research Council of Canada (Grant MT-11717). 2 To whom correspondence should be addressed at Congenital Cardiac Surgery, 3H2.04 WCM Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2B7. Fax: (403)-492-8052.
PY - 1998/10
Y1 - 1998/10
N2 - 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. Materials and 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. Conclusion. During reperfusion of neonatal rabbit hearts, addition of pyruvate improves cardiac performance in association with activation of PDC.
AB - 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. Materials and 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. Conclusion. During reperfusion of neonatal rabbit hearts, addition of pyruvate improves cardiac performance in association with activation of PDC.
KW - Myocardial function
KW - Myocardial metabolism
KW - Newborn
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U2 - 10.1006/jsre.1998.5397
DO - 10.1006/jsre.1998.5397
M3 - Article
C2 - 9758733
AN - SCOPUS:0032189980
VL - 79
SP - 164
EP - 169
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 2
ER -