Dose-dependent changes in cardiac function, strain and remodelling in a preclinical model of heart base irradiation

Mihaela Ghita-Pettigrew*, Kevin S. Edgar, Refik Kuburas, Kathryn H. Brown, Gerard M. Walls, Cecilia Facchi, David J. Grieve, Chris J. Watson, Alan McWilliam, Marcel van Herk, Kaye J. Williams, Karl T. Butterworth

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
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Abstract

Background and purpose
Radiation induced cardiotoxicity (RICT) is as an important sequela of radiotherapy to the thorax for patients. In this study, we aim to investigate the dose and fractionation response of RICT. We propose global longitudinal strain (GLS) as an early indicator of RICT and investigate myocardial deformation following irradiation.

Methods
RICT was investigated in female C57BL/6J mice in which the base of the heart was irradiated under image-guidance using a small animal radiation research platform (SARRP). Mice were randomly assigned to a treatment group: single-fraction dose of 16 Gy or 20 Gy, 3 consecutive fractions of 8.66 Gy, or sham irradiation; biological effective doses (BED) used were 101.3 Gy, 153.3 Gy and 101.3 Gy respectively. Longitudinal transthoracic echocardiography (TTE) was performed from baseline up to 50 weeks post-irradiation to detect structural and functional effects.

Results
Irradiation of the heart base leads to BED-dependent changes in systolic and diastolic function 50 weeks post-irradiation. GLS showed significant decreases in a BED-dependent manner for all irradiated animals, as early as 10 weeks after irradiation. Early changes in GLS indicate late changes in cardiac function. BED-independent increases were observed in the left ventricle (LV) mass and volume and myocardial fibrosis.

Conclusions
Functional features of RICT displayed a BED dependence in this study. GLS showed an early change at 10 weeks post-irradiation. Cardiac remodelling was observed as increases in mass and volume of the LV, further supporting our hypothesis that dose to the base of the heart drives the global heart toxicity.

Original languageEnglish
Article number110113
Number of pages9
JournalRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Volume193
Early online date10 Feb 2024
DOIs
Publication statusPublished - Apr 2024

Keywords

  • Cardiac strain
  • Cardiac toxicity
  • Heart base
  • Mouse model
  • Preclinical radiotherapy
  • Small animal radiotherapy

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