B-po04-128 functional effects of gamma radiation on human cardiomyocytes

Stereotactic ablative radiotherapy (SABR) has recently been used for treatment of ventricular tachycardia (VT), commonly with 25 Gy delivered over a single treatment. However, the anti-arrhythmic effects of SABR on cardiac tissues remain poorly characterized and the functional effects of radiation on cardiac myocytes are unclear. We developed an in vitro method to evaluate the biomechanical effects of radiation on engineered human heart tissues (EHTs). Thin, decellularized porcine left ventricle strips were seeded with human induced pluripotent stem cell-derived cardiomyocytes and human adult cardiac fibroblasts. The resulting EHTs were cultured for 1 week and exposed to a single dose of 0 Gy (control), 12.5 Gy, or 25 Gy gamma radiation. EHTs were cultured for an additional 2 weeks before passive and active contractile behavior was assessed. Spontaneous beat frequency was measured two hours after exposure and then daily for two weeks. Two weeks after exposure no significant differences were observed between control and radiation-treated EHTs. Peak systolic force at 1Hz, time to peak force, time from peak force to 50% relaxation, passive tissue stiffness, maximum Frank-Starling gain, and post-rest potentiation were all similar (Figure, A-F). Spontaneous beating rates were significantly elevated hours following radiation in a dose-dependent manner, but recovered by two days (Figure, G-H). Short-term mechanical measurement suggests limited effects of radiation on human EHTs. Additional electrophysiological studies are planned, and may clarify the mechanisms through which SABR exerts anti-arrhythmic effects.