The Potential Therapeutic Effects of Carbon Ion Beams and X-Rays on Mice with Heart Failure: Preliminary Results

Abstract

<h3>Purpose/Objective(s)</h3> In general, the heart has been recognized as an organ at risk because of adverse events associated with irradiation. However, in recent years, beneficial effects of stereotactic body radiotherapy on refractory arrhythmias have been reported. Therefore, this study investigated the effects of radiation on the diseased heart. <h3>Materials/Methods</h3> A mouse model with cardiac hypertrophy and heart failure induced by transverse aortic constriction (TAC) was irradiated with 30 Gy X-rays or carbon ion beams at 2 weeks after pressure overload and then underwent echocardiography. Fractional shortening (FS) was used to assess cardiac function and left ventricular end-diastolic diameter (LVDd) was used to assess cardiac enlargement. Mice were sacrificed at 4 weeks after irradiation, and heart weight and fibrosis of the myocardium were assessed. <h3>Results</h3> Each group comprised four mice, except for the group that underwent TAC and X-ray irradiation, which comprised five mice. The average values are described. Two weeks after TAC, FS had decreased from 50.9% to 31.3%, and LVDd had increased from 2.6 mm to 3.7 mm. This confirmed that the TAC procedure was successful. In the control group, the FS change ratio (before irradiation versus 4 weeks after irradiation) was 1.06 (50.0% to 53.1%) in non-irradiated mice, 1.18 (51.7% to 60.9%) in mice irradiated with X-rays, and 1.11 (53.1% to 58.7%) in mice irradiated with carbon ion beams. Meanwhile, the LVDd change ratio (before irradiation versus 4 weeks after irradiation) was 1.01 (2.9 mm to 2.9 mm) in non-irradiated mice, 0.90 (2.7 mm to 2.5 mm) in mice irradiated with X-rays, and 0.85 (2.8 mm to 2.4 mm) in mice irradiated with carbon ion beams. In the TAC group, the FS change ratio (before irradiation versus 4 weeks after irradiation) was 0.75 (29.4% to 22.3%) in non-irradiated mice, 1.01 (35.1% to 35.5%) in mice irradiated with X-rays, and 1.36 (29.4% to 39.9%) in mice irradiated with carbon ion beams. Meanwhile, the LVDd change ratio (before irradiation versus 4 weeks after irradiation) was 0.92 (3.8 mm to 3.5 mm) in non-irradiated mice, 0.73 (3.4 mm to 2.5 mm) in mice irradiated with X-rays, and 0.67 (3.8 mm to 2.5 mm) in mice irradiated with carbon ion beams. In the control group, irradiation did not significantly improve cardiac function, but cardiac enlargement was significantly improved by carbon ion beams (P=0.036) and tended to be improved by X-rays (P=0.094). In the TAC group, cardiac function was significantly improved by carbon ion beams (P=0.041) but not by X-rays (P=0.212). Furthermore, cardiac enlargement was significantly improved by carbon ion beams (P=0.036) and tended to be improved by X-rays (P=0.080). Irradiation did not significantly affect heart weight or fibrosis in the control or TAC group. <h3>Conclusion</h3> Irradiation had no observed adverse effects on normal or failing hearts. In the TAC group, irradiation improved cardiac function and enlargement.