Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan;22(1):90-99.
doi: 10.1016/j.hrthm.2024.06.043. Epub 2024 Jun 25.

Cardiac stereotactic body radiotherapy to treat malignant ventricular arrhythmias directly affects the cardiomyocyte electrophysiology

Christine Mages  1 , Heike Gampp  2 , Ann-Kathrin Rahm  1 , Juline Hackbarth  2 , Julia Pfeiffer  2 , Finn Petersenn  2 , Xenia Kramp  2 , Fatemeh Kermani  3 , Juan Zhang  4 , Daniel A Pijnappels  4 , Antoine A F de Vries  4 , Katharina Seidensaal  5 , Bernhard Rhein  5 , Jürgen Debus  5 , Nina D Ullrich  6 , Norbert Frey  1 , Dierk Thomas  7 , Patrick Lugenbiel  8
Affiliations
Free article

Cardiac stereotactic body radiotherapy to treat malignant ventricular arrhythmias directly affects the cardiomyocyte electrophysiology

Christine Mages et al. Heart Rhythm. 2025 Jan.
Free article

Abstract

Background: Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood.

Objective: We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression.

Methods: After exposure to 20 Gy of x-rays in a single fraction, neonatal rat ventricular cardiomyocytes were analyzed 24 and 96 hours postradiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration in both monolayers and single cells. In addition, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and messenger RNA levels.

Results: After irradiation with 20 Gy, neonatal rat ventricular cardiomyocytes exhibited increased beat rate and conduction velocity 24 and 96 hours after treatment. Messenger RNA and protein levels of ion channels were altered, with the most significant changes observed at the 96-hour mark. Upregulation of Cacna1c (Cav1.2), Kcnd3 (Kv4.3), Kcnh2 (Kv11.1), Kcnq1 (Kv7.1), Kcnk2 (K2P2.1), Kcnj2 (Kir2.1), and Gja1 (Cx43) was noted, along with improved gap junctional coupling. Calcium handling was affected, with increased Ryr2 ryanodin-rezeptor 2 and Slc8a1 Na+/Ca2+ exchanger expression and altered properties 96 hours posttreatment. Fibroblast and myofibroblast levels remained unchanged.

Conclusion: cSBRT modulates the expression of various ion channels, calcium handling proteins, and gap junction proteins. The described alterations in cellular electrophysiology may be the underlying cause of the immediate antiarrhythmic effects observed after cSBRT.

Keywords: Ion channel; Neonatal rat ventricular cardiomyocytes; Radiation; Remodeling; Sudden cardiac death; Ventricular arrhythmia.

PubMed Disclaimer

Conflict of interest statement

Disclosures Dr Mages acknowledges educational support from Biotronik and Johnson & Johnson, while Dr Rahm acknowledges support from Boston Scientific, Johnson & Johnson, Abbott, and Medtronic. Dr Thomas has received lecture fees/honoraria from various pharmaceutical and medical device companies, including Abbott, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Medtronic, Novartis, Pfizer Pharma, Sanofi-Aventis, and ZOLL CMS. Dr Lugenbiel has received lecture fees from Bayer Vital, Pfizer Pharma, and Bristol Myers Squibb as well as educational support from Boston Scientific and fees/honoraria from Johnson & Johnson and Boston Scientific. The remaining authors have declared no relevant relationships. We declare that no artificial intelligence was used in preparation of the present manuscript.