Calcium-mediated activation of pyruvate dehydrogenase in severely injured postischemic myocardium.
Indirect evidence suggests that activity of pyruvate dehydrogenase (PDH) influences recovery of the myocardium after transient ischemia. The present study examined the relationship between postischemic injury and activity of PDH and the role of mitochondrial calcium uptake for observed changes in PDH activity. Isovolumically beating isolated rat hearts perfused with erythrocyte-enriched buffer containing glucose, palmitate, and insulin were submitted to either 20 or 35 min of no-flow ischemia. After 20 min of no-flow ischemia, hearts exhibited complete recovery of developed left ventricular pressure (DLVP). The proportion of myocardial PDH in the active state was modestly increased to 38% (compared with 13% in control hearts) without a change in glucose oxidation. In contrast, in hearts subjected to 35 min of no-flow ischemia (which exhibited poor recovery of DLVP), there was marked stimulation of glucose oxidation (+460%; P < 0.01) and pronounced increase in the active fraction of PDH to 72% (P < 0.01). Glycolytic flux was not significantly altered. Ruthenium red (6 microM) completely abolished the activation of PDH and the increase in glucose oxidation. The results indicate that variable stimulation of glucose oxidation during reperfusion is related to different degrees of activation of PDH, which depends on the severity of the ischemic injury. Activation of PDH seems to be mediated by myocardial calcium uptake.
Terrand
J
J
Cardiology Center, University Hospital, CH-1211 Geneva 14, Switzerland.
Papageorgiou
I
I
Rosenblatt-Velin
N
N
Lerch
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats
D011768:Pyruvate Dehydrogenase Complex; D002118:Calcium