Low-Dose Cardiac Radiation Improves Electrical Function and Reduces Ventricular Arrhythmogenesis in Mice With...

Area of Science:

• Cardiology
• Radiation Oncology
• Electrophysiology

Background:

• Clinical cardiac radiation therapy (RT) at 25 Gy reduces ventricular tachycardia (VT).
• Low-dose RT (LDRT) at 5 Gy improved left ventricular ejection fraction (LVEF) in nonischemic cardiomyopathy (NICM) mice, potentially by reducing macrophages.
• The effect of LDRT on VT in NICM remains uninvestigated.

Purpose of the Study:

• To investigate the effects of LDRT on ventricular tachycardia (VT) in a mouse model of nonischemic cardiomyopathy (NICM).

Main Methods:

• Nonischemic cardiomyopathy (NICM) was induced in ACSL1^TG mice.
• Mice received either LDRT (5 Gy) or sham treatment.
• Echocardiography, epicardial mapping, norepinephrine challenge, and assessment of cardiac sympathetic innervation were performed.
• Macrophage depletion using anti-CSF1R antibody was employed to study their role.

Main Results:

• LDRT significantly improved LVEF and reduced ventricular arrhythmias (VA) in NICM mice.
• LDRT enhanced cardiac electrical properties, including faster conduction velocity and lower activation time.
• LDRT increased sympathetic nerve density and reduced innervation heterogeneity.
• Macrophage depletion improved LVEF but did not affect VA, conduction, or activation time, despite increasing nerve density.

Conclusions:

• LDRT ameliorates cardiac dysfunction and reduces spontaneous VA in NICM mice.
• Improved sympathetic nerve distribution, not macrophage reduction, correlates with LDRT's antiarrhythmic effects.
• Further research is warranted to elucidate the precise antiarrhythmic mechanisms of LDRT.