It has been known that
heart disease-such as
myocardial infarction (MI),
cardiac hypertrophy, or
heart failure-alters the molecular structure and function of the gap junction, which can lead to an abnormal heart rhythm. Radiation has been shown to modulate intercellular communication in the skin and lungs by increasing
connexin43 (
Cx43) expression. Understanding how
Cx43 upregulation is induced in a diseased heart can help provide a new perspective to
radiation therapy for arrhythmias. In a recent study with rabbits after MI,
carbon ions were accelerated to 290 MeV/u and extracted in the air; a biologically (cell kill) uniform 6-cm spread-out Bragg peak beam was generated, and beam tissue depth was set to 30 mm with energy degraders to the depth position. Targeted heavy ion irradiation (THIR) with 15 Gy to the left ventricle increased
Cx43 expression, improved conductivity, decreased the spatial heterogeneity of repolarization, and reduced the vulnerability of rabbit hearts to ventricular arrhythmias after MI. In clinically normal rabbits, THIR > = 10 Gy caused a significant dose-dependent increase of
Cx43 protein and
messenger RNA 2 weeks after irradiation. The left (irradiated) and right (nonirradiated) ventricles exhibited circumferential upregulation of
Cx43 lasting for at least 1 year. There were no significant changes in electrocardiograms and echocardiograms, indicating no apparent injury for 1 year. A single exposure of 135 MeV/u THIR with 15 Gy to a dog heart attenuated vulnerability to ventricular
arrhythmia after the induction of MI for at least 1 year through the modulation of
Cx43 expression. This long-lasting remodeling effect on gap junctions may lay the groundwork to novel
therapies against life-threatening ventricular arrhythmias in structural
heart disease. To date, there have been few investigations into the effects of
carbon-ion irradiation on electrophysiological properties in the human heart. Patients with
mediastinum cancer were investigated for 5 years
after treatment that included irradiation to the heart, and investigators found that
carbon-ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of
arrhythmia reduction. Its practical application in non-
cancer treatment, such as in
arrhythmia treatment, is highly anticipated.