Effects of Irradiation on Cardiac Tissue: An Explanation For a Novel Treatment of Ventricular Tachycardia

Uri Goldsztejn 1,2 Adam Lang 4 Phillip Cuculich 2 Clifford Robinson 3 Julie Schwartz 3 Stacey Rentschler 1,2
1Washington University School of Medicine, USA
2Washington University School of Medicine, USA
3Washington University School of Medicine, USA
4Washington University School of Medicine, USA

A recent study done in collaboration between clinical investigators from radiation oncology and cardiology, from Washington University in St. Louis, showed for the first time the feasibility of treating ventricular tachycardia with targeted irradiation. The successful results of this study are being replicated in other centers, raising interest rapidly. Despite the efficacy of this therapy, the cellular mechanisms that mediate the effects of irradiation on cardiac electrophysiology remain unknown. We have found that fibrosis formation and scar homogenization does not account for the clinical effects observed. This observation raises great interest in the study of the cardiac electrophysiological effects of targeted irradiation. An irradiation plan that targets the whole murine heart, while sparing adjacent organs in vivo, has been developed and validated. Electrocardiographic and optical mapping studies on this model show a prolonged conduction wavelength that becomes evident at timeframes similar to the clinical observations. Moreover, simulation results that incorporate the production of reactive oxygen species after irradiation in a fiber model predict similar results. These preliminary results strongly suggest that the mechanism of action of this treatment involves conduction remodeling rather than scar homogenization.

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