Calcium-mediated activation of pyruvate dehydrogenase in severely injured postischemic myocardium

Citation
J. Terrand et al., Calcium-mediated activation of pyruvate dehydrogenase in severely injured postischemic myocardium, AM J P-HEAR, 281(2), 2001, pp. H722-H730
Citations number
44
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
ISSN journal
03636135 → ACNP
Volume
281
Issue
2
Year of publication
2001
Pages
H722 - H730
Database
ISI
SICI code
0363-6135(200108)281:2<H722:CAOPDI>2.0.ZU;2-B
Abstract
Indirect evidence suggests that activity of pyruvate dehydrogenase (PDH) in fluences recovery of the myocardium after transient ischemia. The present s tudy examined the relationship between postischemic injury and activity of PDH and the role of mitochondrial calcium uptake for observed changes in PD H activity. Isovolumically beating isolated rat hearts perfused with erythr ocyte-enriched buffer containing glucose, palmitate, and insulin were submi tted to either 20 or 35 min of no-flow ischemia. After 20 min of no-flow is chemia, hearts exhibited complete recovery of developed left ventricular pr essure (DLVP). The proportion of myocardial PDH in the active state was mod estly increased to 38% (compared with 13% in control hearts) without a chan ge in glucose oxidation. In contrast, in hearts subjected to 35 min of no-f low ischemia (which exhibited poor recovery of DLVP), there was marked stim ulation of glucose oxidation (+460%; P< 0.01) and pronounced increase in th e active fraction of PDH to 72% (P< 0.01). Glycolytic flux was not signific antly altered. Ruthenium red (6 muM) completely abolished the activation of PDH and the increase in glucose oxidation. The results indicate that varia ble stimulation of glucose oxidation during reperfusion is related to diffe rent degrees of activation of PDH, which depends on the severity of the isc hemic injury. Activation of PDH seems to be mediated by myocardial calcium uptake.