Abstract 3930: Inhibition of the Malate-aspartate Shuttle Abolishes Cardioprotection by Postconditioning in Rat Hearts
Objective: To investigate the importance of the malate-aspartate shuttle (MAS) for cardioprotection by ischemic postconditioning (iPCON). Furthermore, we studied whether postconditioning (iPCON) modulates metabolism of L-glutamate, a key metabolite of the MAS.
Methods: Isolated rat hearts were perfused with glucose and subjected to 40 min of global ischemia followed by 120 min reperfusion. iPCON was induced by 6 cycles of 10 sec reperfusion/10 sec ischemia. To inhibit the MAS the amino acid transaminase inhibitor aminooxyacetate (AOA: 0.025 mM) was administered during reperfusion. Hearts were allocated to 4 groups:
Control + AOA and
iPCON + AOA (N=10 in each group) and infarct size and hemodynamic recovery were evaluated.
Coronary effluent, microdialysis and myocardial tissue were collected for metabolic measurements.
Results: iPCON significantly reduced infarct size when compared to control. Inhibition of the MAS by AOA abolished the infarct reducing effect by postconditioning (Figure 1A⇓). Myocardial release of glutamate was significantly decreased during iPCON (P<0.001) compared to controls. iPCON significantly increased myocardial glutamate concentration by 45% (P<0.01) compared to control (Figure 1B⇓). There were no significant differences in myocardial glutamate concentration following 45 min reperfusion, suggesting an increased glutamate utilization (Figure 1B⇓).
Conclusion: Activity of the malate-aspartate shuttle is crucial for cardioprotection by iPCON. The mechanisms underlying iPCON includes myocardial glutamate metabolism.