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Cardiac stereotactic body radiotherapy to treat malignant ventricular arrhythmias directly affects the cardiomyocyte electrophysiology.
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.
Afiliación
  • Mages C; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner site Heidelberg/Mannheim, University of Heidelberg, Heidel
  • Gampp H; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany.
  • Rahm AK; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner site Heidelberg/Mannheim, University of Heidelberg, Heidel
  • Hackbarth J; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany.
  • Pfeiffer J; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany.
  • Petersenn F; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany.
  • Kramp X; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany.
  • Kermani F; Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, Heidelberg, Germany.
  • Zhang J; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Pijnappels DA; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
  • de Vries AAF; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Seidensaal K; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.
  • Rhein B; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.
  • Debus J; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.
  • Ullrich ND; German Centre for Cardiovascular Research (DZHK), Partner site Heidelberg/Mannheim, University of Heidelberg, Heidelberg, Germany; Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, Heidelberg, Germany; Department of Physiology, University of Bern, Bern, Switzerland.
  • Frey N; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner site Heidelberg/Mannheim, University of Heidelberg, Heidel
  • Thomas D; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner site Heidelberg/Mannheim, University of Heidelberg, Heidel
  • Lugenbiel P; Department of Cardiology, University Hospital Heidelberg, Heidelberg, Germany; Heidelberg Center for Heart Rhythm Disorders (HCR), University Hospital Heidelberg, Heidelberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner site Heidelberg/Mannheim, University of Heidelberg, Heidel
Heart Rhythm ; 2024 Jun 25.
Article en En | MEDLINE | ID: mdl-38936449
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heart Rhythm Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heart Rhythm Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos