Amino acid transamination is crucial for ischaemic cardioprotection in normal and preconditioned isolated rat hearts – focus on l‐glutamate

Abstract

We have found that cardioprotection by l-glutamate mimics protection by classical ischaemic preconditioning (IPC). We investigated whether the effect of IPC involves amino acid transamination and whether IPC modulates myocardial glutamate metabolism. In a glucoseperfused, isolated rat heart model subjected to 40 min global no-flow ischaemia and 120 min reperfusion, the effects of IPC (2 cycles of 5 min ischaemia and 5 min reperfusion) and continuous glutamate (20 mm) administration during reperfusion on infarct size and haemodynamic recovery were studied. The effect of inhibiting amino acid transamination was evaluated by adding the amino acid transaminase inhibitor amino-oxyacetate (AOA; 0.025 mm) during reperfusion. Changes in coronary effluent, interstitial (microdialysis) and intracellular glutamate ([GLUT] i ) concentrations were measured. Ischaemic preconditioning and postischaemic glutamate administration reduced infarct size to the same extent (41 and 40%, respectively; P < 0.05 for both), without showing an additive effect. Amino-oxyacetate abolished infarct reduction by IPC and glutamate, and increased infarct size in both control and IPC hearts in a dose-dependent manner. Ischaemic preconditioning increased [GLUT] i before ischaemia (P < 0.01) and decreased the release of glutamate during the first 10 min of reperfusion (P = 0.03). A twofold reduction in [GLUT] i from the preischaemic state to 45 min of reperfusion (P = 0.0001) suggested increased postischaemic glutamate utilization in IPC hearts. While IPC and AOA changed haemodynamics in accordance with infarct size, glutamate decreased haemodynamic recovery despite reduced infarct size. In conclusion, ischaemic cardioprotection of the normal and IPC-protected heart depends on amino acid transamination and activity of the malate-aspartate shuttle during reperfusion. Underlying mechanisms of IPC include myocardial glutamate metabolism.

Integrative Computational and Experimental Approaches to Establish a Post-Myocardial Infarction Knowledge Map

“…Currently, there are very few studies on the role of L-glutamate post-MI. Lofgren et al found that L-glutamate provides cardioprotection in the same manner as classical ischemic preconditioning [34].…”

Comparison of two sulfonylureas with high and low myocardial KATP channel affinity on myocardial infarct size and metabolism in a rat model of type 2 diabetes

“…Increased myocardial glutamate content in the non-ischaemic diabetic hearts may be a compensatory mechanism secondary to a decreased level of mitochondrial glutamate transporters in order to sustain mitochondrial function. In further support of mitochondrial dysfunction in diabetic hearts, glutamate affords cardioprotection, which involves the malate-aspartate shuttle [34], and an increased glutamate concentration is required to elicit protection against ischaemia/reperfusion (IR) injury in diabetic compared with non-diabetic animals [33]. As the modulation of mitochondrial K ATP channels by gc and gb is different [29,35] gc treatment did not influence cardiac amino acid or mitochondrial metabolism.…”

Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure

“…It was connected to a pressure-controlled Langendorff system as previously described. 22 Krebs-Henseleit buffer was used as perfusion media, gassed with 95% O 2 and 5% CO 2 to keep the pH at 7.4 and the heart oxygenated.…”