Abstract 591: Non-Invasive Analysis of Oxidative Stress in Myocardial Remodeling and Failure in Mice Using in vivo Electron Spin Resonance (ESR) Spectroscopy
Oxidative stress plays an important role in the development and progress of myocardial remodeling and failure. We have demonstrated that the generation of reactive oxygen species (ROS) is enhanced in the tissue homogenates obtained from the failing hearts in vitro by electron spin resonance (ESR) spectroscopy (Ide, Circ Res 2000, 86, 152). However, there is no direct evidence of ROS generation in the hearts in vivo. Therefore, the aim of this study was to assess the time-dependent changes of ROS generation in the hearts after myocardial infarction(MI) using a technique of in vivo ESR measurement that has been developed for direct and non-invasive analysis of ROS generation in living animals.We created MI in mice by ligating the left coronary artery and performed in vivo ESR analysis at day 2, 7, 14, and 28 after MI. The in vivo generation of ROS was analyzed by the ESR signal decay of methoxy-PROXYL, a tissue permeable spin probe, injected intravenously. Left ventricular (LV) function was assessed by echocardiography. The ESR signal decay measured at the chest of mice was not changed in MI at day 2, but was increased in MI compared to sham-operated mice at day 7 (Sham vs MI; 0.122±0.005 vs 0.142±0.007/min; p<0.05)and further increased at day 14(0.123±0.004 vs 0.162±0.009/min, p<0.01) and 28 (0.119±0.004 vs 0.161±0.010/min, p<0.01). The accelerated ESR signal decay was associated with the progression of LV dilatation and dysfunction. The increased ESR signal decay in MI was completely suppressed by the administration of antioxidant, Tiron. The ESR signal decay was comparable between groups when measured at the head or the abdomen, indicating that the increase of the signal decay was due to the ROS generation within the heart. It was further confirmed by the increased ESR signal decay in the cardiac homogenates obtained from MI mice. The present study provided the direct evidence in the post-MI living mice that ROS were generated within the hearts during the progression of remodeling and failure.