Mages, Christine; Gampp, Heike; Rahm, Ann-Kathrin; Hackbarth, Juline; Pfeiffer, Julia; Petersenn, Finn; Kramp, Xenia; Kermani, Fatemeh; Zhang, Juan; Pijnappels, Daniel A; de Vries, Antoine A F; Seidensaal, Katharina; Rhein, Bernhard; Debus, Jürgen; Ullrich, Nina D; Frey, Norbert; Thomas, Dierk; Lugenbiel, Patrick (2024). Cardiac stereotactic body radiotherapy to treat malignant ventricular arrhythmias directly affects the cardiomyocyte electrophysiology. (In Press). Heart rhythm Elsevier 10.1016/j.hrthm.2024.06.043
|
Text
1-s2.0-S1547527124028170-main.pdf - Accepted Version Available under License Creative Commons: Attribution (CC-BY). Download (3MB) | Preview |
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.
OBJECTIVES
We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression.
METHODS
Following exposure to 20Gy of X-rays in a single fraction, neonatal rat ventricular cardiomyocytes (NRVCs) were analyzed 24 and 96h post-radiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration (APD) in both monolayers and single cells. Additionally, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and mRNA levels.
RESULTS
Following irradiation with 20Gy, NRVCs exhibited increased beat rate and conduction velocities 24 and 96h after treatment. mRNA and protein levels of ion channels were altered, with the most significant changes observed at the 96h-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 (RYR2) and Slc8a1 (NCX) expression and altered properties 96h post-treatment. Fibroblast and myofibroblast levels remained unchanged.
CONCLUSIONS
CSBRT modulates 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 following cSBRT.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology |
UniBE Contributor: |
Ullrich, Nina Daniela |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1556-3871 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
28 Jun 2024 15:50 |
Last Modified: |
29 Jun 2024 02:25 |
Publisher DOI: |
10.1016/j.hrthm.2024.06.043 |
PubMed ID: |
38936449 |
Uncontrolled Keywords: |
ion channel neonatal rat cardiomyocytes radiation remodeling sudden cardiac death ventricular arrhythmia |
BORIS DOI: |
10.48350/198266 |
URI: |
https://boris.unibe.ch/id/eprint/198266 |
Actions (login required)
 |
Edit item |