Heavy Ion Irradiation Reduces Vulnerability to Atrial Tachyarrhythmias　― Gap Junction and Sympathetic Neural Remodeling

• Published in: Circulation Journal Vol. 87; no. 7; pp. 1016 - 1026
• Main Authors: Amino, Mari, Yamazaki, Masatoshi, Yoshioka, Koichiro, Kawabe, Noboru, Tanaka, Sachie, Shimokawa, Takashi, Niwa, Ryoko, Tomii, Naoki, Kabuki, Shigeto, Kunieda, Etsuo, Yagishita, Atsuhiko, Ikari, Yuji, Kodama, Itsuo
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 23.06.2023
• Subjects: Atrial fibrillation; Connexin; Heavy ion; Nerve sprouting; Remodeling; Heavy ion; Connexin; Nerve sprouting; Remodeling; Atrial fibrillation
• ISSN: 1346-9843; 1347-4820; 1347-4820
• DOI: 10.1253/circj.CJ-22-0527

Background: Low-invasive stereotactic body radiation therapy is a novel anti-arrhythmic strategy. The mechanisms underlying its effects against ventricular tachycardia/fibrillation (VT/VF) are gradually becoming clear, whereas those underlying atrial tachycardia/fibrillation (AT/AF) remain unknown. This study investigated the effects of carbon ion beam on gap junction expression and sympathetic innervation.Methods and Results: Atrial and ventricular tachyarrhythmia models was established in 26 hypercholesterolemic (HC) 3-year-old New Zealand white rabbits; 12 rabbits were irradiated with a single 15-Gy carbon ion beam (targeted heavy ion irradiation [THIR]) and 14 were not (HC group). Eight 3-month-old rabbits (Young) were used as a reference group. In vivo induction frequencies in the Young, HC, and HC+THIR groups were 0%, 9.9%, and 1.2%, respectively, for AT/AF and 0%, 7.8%, and 1.2%, respectively, for VT/VF (P<0.01). The conduction velocity of the atria and ventricles on optical mapping was significantly reduced in the HC group; this was reversed in the HC+THIR group. Connexin-40 immunolabelling in the atria was 66.1–78.7% lower in the HC than Young group; this downregulation was less pronounced in the HC+THIR group (by 23.1–44.4%; P<0.01). Similar results were obtained for ventricular connexin-43. Sympathetic nerve densities in the atria and ventricles increased by 41.9–65.3% in the HC vs. Young group; this increase was reversed in the HC+THIR group.Conclusions: Heavy ion radiation reduced vulnerability to AT/AF and VT/VF in HC elderly rabbits and improved cardiac conductivity. The results suggest involvement of connexin-40/43 upregulation and suppression of sympathetic nerve sprouting.