Carnosine Postconditioning Does not Evoke PI3K/Akt Mediated Cardioprotection in Isolated Rat Heart Upon Ischemia-Reperfusion

Abstract

Purpose Carnosine has preconditioning effects on myocardial ischemia-reperfusion injury; however, its postconditioning effects remain unknown. We aimed to determine whether postischemic treatment with carnosine alleviated injury through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) activation in an isolated rat heart model. Methods Thirty-two male Wistar rat hearts were exposed to ischemia for 15 min using the Langendorff system and randomly assigned to four equal groups. The control (Cont) group received Krebs-Henseleit (KH) buffer over 20 min before and after ischemia. The carnosine (CAR) group received KH buffer before ischemia and 1 mmol/L L-carnosine after reperfusion. The control and wortmannin (Cont + Wort) group received KH buffer with 100 nmol/L wortmannin (a specific PI3K inhibitor) throughout. The carnosine and wortmannin (CAR + Wort) group received KH buffer with wortmannin before ischemia and KH buffer with wortmannin and 1 mmol/L L-carnosine after reperfusion. Indicators of hemodynamics, such as the maximum left ventricular derivative of pressure development (LV dP/dt max), were recorded before and 5, 10, 15, and 20 min after reperfusion. Myocardial phosphorylated and total Akt were measured using Western blotting after 20 min of reperfusion. Results The LV dP/dt max of the CAR group did not increase relative to that in the Cont group at any time point. Western blot analysis did not detect Akt activation in the CAR group relative to the Cont group. The Akt concentration was reduced by wortmannin. Conclusion In an isolated rat heart model, carnosine postconditioning did not improve cardiac contractility or was related to Akt activation after the ischemic insult.

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