Study reveals radiation-induced changes in cardiac cell energy metabolism at doses used in heart arrhythmia treatment
A new preclinical study published on bioRxiv found that ionizing radiation at clinically relevant doses causes dose-dependent disruptions to mitochondrial energy metabolism in mouse cardiac cells and tissue. The research was motivated by the puzzling observation that cardiac stereotactic body radiotherapy (SBRT) for ventricular tachycardia often produces clinical benefits within days—before radiation-induced fibrosis can develop. Understanding these acute bioenergetic changes could help explain the therapy's early effectiveness and inform concerns about long-term cardiotoxicity.
Researchers used mouse cardiomyocyte cell lines (HL-1) and living myocardial slice preparations to study how radiation doses of 10 Gy and 25 Gy—both used in cardiac SBRT—affect heart cell energy systems. At 10 Gy, cells showed signs of acute bioenergetic stress: reduced adenylate energy charge, disrupted cytoskeletal structure, impaired mitochondrial respiration, and increased calcium oscillation amplitude. Surprisingly, 25 Gy exposure led to NAD+ depletion but paradoxically enhanced mitochondrial respiratory capacity, suggesting the higher dose triggers an adaptive metabolic response. In ex vivo myocardial tissue slices, creatine content was reduced but the phosphocreatine-to-ATP ratio was preserved, indicating a degree of metabolic resilience at the tissue level that was not seen in isolated cell cultures. The authors conclude that radiation induces model-specific and dose-specific metabolic perturbations, and that these bioenergetic changes—rather than structural fibrosis—may underlie the rapid antiarrhythmic effects observed clinically. The findings also raise questions about the potential for cumulative metabolic damage contributing to long-term cardiotoxicity in patients receiving cardiac SBRT.
What's missing
As a preprint, this study has not yet undergone peer review. The research is entirely preclinical (mouse cell lines and ex vivo tissue), so direct translation to human cardiac physiology remains unestablished. The study does not address whether the observed bioenergetic changes are causally linked to the antiarrhythmic effects seen clinically, nor does it include in vivo animal data or patient samples. The mechanisms connecting mitochondrial metabolic shifts to suppression of ventricular tachycardia circuits are not fully elucidated. Long-term follow-up data on whether the adaptive responses observed at 25 Gy are sustained or eventually harmful are also absent.
What different sources said
- bioRxivCenter
Radiation-induced disruption of cardiac mitochondrial bioenergetics and nucleotide homeostasis in mice
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