X-ray Radiotherapy Impacts Cardiac Dysfunction by Modulating the Sympathetic Nervous System and Calcium Transients

Area of Science:

• Cardiology
• Radiotherapy
• Molecular Biology

Background:

• Epidemiological studies link radiotherapy for right-sided breast cancer to cardiovascular diseases.
• Patients undergoing radiation therapy (RT) are at increased risk for arrhythmias and conduction disturbances.

Purpose of the Study:

• To investigate the mechanisms of low-to-moderate dose X-ray irradiation (IR) on cardiac function.
• To evaluate changes in the cardiac sympathetic nervous system (CSNS), atrial remodeling, and calcium homeostasis after IR.
• To identify pro-arrhythmic mechanisms and potential prevention strategies during RT for breast cancer.

Main Methods:

• Female C57Bl/6J mice were exposed to X-ray doses (0.25–2 Gy) mimicking RT for right-sided breast cancer.
• Cardiac function was assessed using Doppler ultrasound at 60 weeks post-irradiation.
• Cardiac fibrosis, apoptosis, calcium transient protein expression, and CSNS were analyzed.

Main Results:

• Low-dose IR (≥0.25 Gy) induced late cardiac and atrial dysfunction, reduced myocardial strain, ejection fraction, and atrial function.
• Significant epicardial fibrosis and apoptosis were observed at 0.5 Gy.
• IR altered ventricular CSNS structure and expression of calcium transient proteins, affecting cardiac contractility and potentially causing arrhythmias.

Conclusions:

• Local heart irradiation, even at low doses, can lead to late cardiac dysfunction and fibrosis.
• Irradiation-induced alterations in CSNS and calcium handling contribute to cardiac rhythm disturbances.
• Findings offer insights into preventing radiation-induced arrhythmias in breast cancer patients.