Background

For patients with ventricular tachycardia (VT) and failed standard therapy, only limited therapeutic options are currently available. Cardiac stereotactic body radiation therapy (SBRT) has emerged as a promising new noninvasive treatment option for refractory VTs. Reduction of VT burden is observed within days to weeks after irradiation, but the cellular electrophysiological mechanism underlying the early antiarrhythmic effect is still poorly understood. Our aim was to test the effects of 20 Gy ionizing radiation on ventricular neonatal rat cardiac electrophysiology at time periods from 24 hours to 96 hours after irradiation.

Methods

Ventricular neonatal rat cardiomyocytes were isolated, cultivated for 24 hours and then irradiated with the X-ray irradiation unit X-RAD 320. Using Western Blot data and immunofluorescent staining, changes in protein expression of ion channels, calcium handling proteins and connexins were analyzed. Gap junction-mediated intercellular coupling was assessed by fluorescence recovery after photobleaching (FRAP). Action potentials were recorded using the whole-cell voltage clamp technique in current- clamp mode. Contractile properties and calcium handling were analyzed.

Results

Irradiation with 20 Gy lead to increased levels of cardiac conduction proteins at 96 hours after irradiation, notably the L-type calcium channel and repolarizing potassium channels. Connexin 43 (Cx43) expression was significantly increased and intercellular coupling was improved. The beat rate increase correlated with a shift in action potential duration and change in action potential morphology. Irradiated cardiomyocytes showed altered contraction dynamics. 

Conclusion

Our study presents findings to suggest that early antiaarhythmic effects occur independently of fibrosis. Irradiation causes acute changes of connexin and ion channel expression. These changes are connected to functional electrophysiologic changes and improved conduction. Thus, irradiation could potentially act antiarrhythmic through cellular electrical remodelling and effects on action potential duration and conduction velocity.