EC Emergency Medicine And Critical Care

The heart utilizes ketone bodies in preference to fatty acids and glucose under normal condition. This study was carried out to in- vestigate the effect of global no-flow ischemia and chemical stress condition on the utilization of D-3-hydroxybutyrate (D-3-HB) and glucose with reference to the AMP-activated protein kinase (AMPK) and p38 mitogen activated protein kinase (p38 MAPK) signaling cascades in the isolated perfused heart. 2,4-dinitrophenol (DNP) and anisomycin (Aniso) are used to mimic hypoxia and ischemia respectively. DNP stimulated D-3-HB and glucose utilization. D-3-HB decreased the DNP-and Insulin-stimulated glucose utilization. The stimulatory effects of Insulin and DNP on glucose utilization were additive. Insulin and DNP enhanced D-3-HB utilization and the stimulatory effects of Insulin and DNP were not additive. Global no-flow ischemia-reperfusion, ionomycin (Iono) an activator of Ca2+ -calmodulin-dependent protein kinase kinase (CaMKK) and anisomycin an activator of p38 MAPK stimulate the utilization of D-3-HB. STO-609 and PD-169316 are a selective inhibitor of CaMKK and p38 MAPK respectively. STO-609 and PD-169316 abolished the increase in D-3-HB utilization in response to ionomycin, anisomycin, and global no-flow ischemia-reperfusion. We conclude that these results indicate the involvement of AMPK and p38 MAPK in the regulation of D-3-HB and glucose utilization during stress, and global no-flow ischemia. Stimulatory effect on D-3-HB utilization could be mediated via the AMPK and p38 MAPK signaling cascades.

 Keywords: D-3-hydroxybutyrate; Glucose; AMPK; p38 MAPK; Cardiac Metabolism; Ischemia

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