Non-invasive evaluation of free radical reactions accompanied with induction and development of heart failure by in vivo ESR-CT

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Failing myocardium is a final stage of several types of heart diseases, and the prognosis is the similarly worst as malignant tumor. Therefore, an establishment of preventive method should be essential. Recently, participation of free radicals belonging to reactive oxygen species and reactive nitrogen species in the induction and development of failing myocardium through in vivo cross-talk among free radicals and collapse of redox balance was indicated.In order to evaluate the fluctuation of redox balance in individuals, it is best way to evaluate temporal-spatial fluctuation of free radical reactions by imaging techniques. In our latest study, we established in vivo ESR-CT system using nitroxyl spin probes, and applied it to non-invasive evaluation of free radical reactions in living mice with several types of diseases. This technique is usable for elucidating a correlation between free radical reactions and failing myocardium in individual organism level and molecular level.In the present study, we examined a participation of free radicals in the induction and development of failing myocardium using model dogs. As a result, we proved that free radical generation was significantly enhanced, while activities of anti-oxidant enzymes did not fluctuated. Through this experiment, we elucidated that electron transfer system in mitochondria is a main source of these free radicals. In fact, there is a significantly negative correlation between the regeneration of transplanted heart and the degree of free radical generation. On the other hand, we established a novel algorithm for imaging of free radicals in individual, and succeeded to simultaneously determined reactive oxygen species and reactive nitrogen species.