Study reveals radiation-induced changes in cardiac cell energy metabolism at doses used in heart arrhythmia treatment
Researchers exposed mouse heart cells and tissue to radiation doses used in cardiac stereotactic body radiotherapy (SBRT) and found dose-dependent disruptions in mitochondrial energy production and metabolic markers. The study suggests that immediate metabolic changes, rather than delayed tissue scarring, may explain why SBRT rapidly improves certain heart arrhythmias in patients. The findings could inform understanding of both the therapeutic benefits and potential long-term side effects of this emerging treatment.
A preprint study published on bioRxiv investigated how ionizing radiation affects cardiac cell metabolism using mouse cardiomyocytes and heart tissue slices exposed to clinically relevant radiation doses (10 Gy and 25 Gy). At 10 Gy, radiation induced acute metabolic stress marked by reduced energy charge, disrupted cell structure, impaired mitochondrial respiration, and increased calcium oscillations. At the higher 25 Gy dose, cells showed NAD+ depletion but paradoxically enhanced mitochondrial respiratory capacity, suggesting an adaptive response. Whole tissue samples demonstrated reduced creatine but maintained overall energy balance, indicating metabolic resilience at the tissue level. The researchers conclude that these dose- and model-dependent metabolic alterations may explain the rapid clinical benefits of cardiac SBRT for treating refractory ventricular tachycardia, which occur before radiation-induced scarring develops.
What's missing
The study is a preprint and has not undergone peer review. The authors note model-specific responses (differences between isolated cells and intact tissue), which limits direct extrapolation to human cardiac physiology. The mechanisms linking these acute metabolic changes to the clinical antiarrhythmic effect remain to be established. Long-term cardiotoxicity outcomes in animal models or patients are not addressed.
What different sources said
- bioRxivCenter
Radiation-induced disruption of cardiac mitochondrial bioenergetics and nucleotide homeostasis in mice
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