Electrophysiological and Pathological Impact of Medium-Dose External Carbon Ion and Proton Beam Radiation on the Left Ventricle in an Animal Model

• Published in: Journal of the American Heart Association 2021-04, Vol.10 (7), p.e019687
• Main Authors: Takami, Mitsuru, Hara, Tetsuya, Okimoto, Tomoaki, Suga, Masaki, Fukuzawa, Koji, Kiuchi, Kunihiko, Suehiro, Hideya, Akita, Tomomi, Takemoto, Makoto, Nakamura, Toshihiro, Sakai, Jun, Yatomi, Atsusuke, Nakasone, Kazutaka, Sonoda, Yusuke, Yamamoto, Kyoko, Takahara, Hiroyuki, Hirata, Ken-Ichi
• Format: Article
• Language: English
• Subjects: Animals; carbon ion beam; Dose-Response Relationship, Radiation; Electrophysiologic Techniques, Cardiac - methods; electrophysiology; Heart Ventricles - diagnostic imaging; Heart Ventricles - physiopathology; Heart Ventricles - radiation effects; Heavy Ion Radiotherapy - methods; Myocardium - pathology; Original Research; proton beam; Proton Therapy - methods; Rabbits; radiation; Radiation Injuries, Experimental - diagnosis; Radiation Injuries, Experimental - physiopathology; Tachycardia, Ventricular - diagnosis; Tachycardia, Ventricular - physiopathology; Tachycardia, Ventricular - radiotherapy; Tomography, X-Ray Computed; ventricular arrhythmia; Ventricular Function, Left - radiation effects
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/jaha.120.019687

Background Medium-dose (25 gray) x-ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x-ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium-dose carbon ion and proton beam radiation in the left ventricle (LV). Methods and Results External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3-month or 6-month follow-up, the animals underwent an open-chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed. Conclusions Medium-dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.