Sawa Y. Activated protein C has a protective effect against myocardial I/R injury by improvement of endothelial function and activation of AKT1. PLoS ONE

Objectives: Activated protein C (APC) has a protective efficacy against ischemia-reperfusion (I/R) injury in several organs. The objective of this study was to investigate effect of APC in myocardium with possible mechanism. Methods: We used regional and global myocardial I/R injury models of rats. They consisted of I/R injuries (1) by ligation of left coronary artery, or (2) using Langendorff apparatus. Langendorff was used to focus the mechanism of APC excluding coagulation cascade in a working heart. Each experiment had an APC group (n = 10) and a control group with normal saline (n = 10). Injections of these solutions into rats were performed 30 minutes before the planned-I/R injury. Cardiac performance after the procedure was evaluated by echocardiography or indices with Langendorff apparatus. Coronary flow (CF) was measured in the global I/R injury model. Western blotting was performed to detect the change of AKT1 signal in myocardium after global I/R injury. Results: LV function improved significantly in the APC group: %EF at 2 weeks after procedure, 70.8%64.5 % vs. 56.5%60.7%; APC vs. control; p,0.01. Percent LV development pressure (LVDP) also improved in the APC group significantly, 88.8%645.3 % vs. 28.1%615.4%; APC vs. control; p,0.01. In APC group, %CF improved significantly, 88.5%615.8 % vs. 65.0%613.4%; APC vs. control; p,0.01. It was enhanced significantly when acetylcholine was administered; % CF: 103.5%69.9 % vs. 87.0%612.1%; APC vs. control; p,0.05. Western blotting revealed that APC significantly induce