Erythropoietin protects the human myocardium against hypoxia/reoxygenation injury via phosphatidylinositol‐3 kinase and ERK1/2 activation

Background and purposes: Erythropoietin (EPO) has been shown to protect against myocardial infarction in animal studies by activating phosphatidylinositol‐3 kinase (PI3K)/Akt and ERK1/2. However these pro‐survival pathways are impaired in the diabetic heart. We investigated the ability of EPO to protect human atrial trabeculae from non‐diabetic and diabetic patients undergoing coronary artery bypass surgery, against hypoxia‐reoxygenation injury. Experimental approach: Human atrial trabeculae were exposed to 90min hypoxia and 120min reoxygenation. EPO was administered throughout reoxygenation. The developed force of contraction, calculated as a percentage of baseline force of contraction, was continuously monitored. The involvement of PI3K and ERK1/2 and the levels of activated caspase 3(AC3) were assessed. Key results: EPO improved the force of contraction in tissue from non‐diabetic patients (46.7+/‐1.7% vs. 30.2+/‐2.2% in control, p