Combination of Ischemic Postconditioning and Pharmacological Reperfusion Treatment Abrogates Cardioprotection

Aims: The main aim of this project was to explore if the combination of ischemic postconditioning (IPost) with pharmacological reperfusion treatments (insulin and GSK- 3β inhibition) could further reduce infarct size as compared to the treatments administered separately, and whether this was mediated via Akt signaling. Secondly, we explored the role of ROS in the cardioprotection afforded by the various treatments. Methods: Langendorff perfused ex vivo rat hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion. Hearts were treated with IPost, insulin, GSK-3β inhibitor (GSK3i) separately or in combination. MPG was employed to investigate the role of ROS in the cardioprotection afforded by the treatments. Tissue for analyzing the phosphorylation status of Akt was isolated at 15 min of reperfusion. Results: Conditioning ex vivo rat hearts with IPost, GSK3i or insulin from the onset of reperfusion significantly reduced infarct size by 32%, 48% and 48%, respectively (p