Inducibility of Ventricular Arrhythmia 1 Year Following Treatment with Heavy Ion Irradiation in Dogs with Myocardial Infarction.
BACKGROUND
Targeted external heavy ion irradiation (THIR) of rabbit hearts 2 weeks after myocardial infarction (MI) reduced the vulnerability of fatal ventricular tachyarrhythmias (VT/VF) in association with the increased connexin43 (Cx43). Increased Cx43 was maintained for at least 1 year in normal rabbits, but the long-term antiarrhythmic effects in the MI model are unknown. We investigated the propensity for late potentials and VT/VF inducibility.


METHODS
Intracoronary injection of microspheres was performed to induce nontransmural MI in anesthetized eight beagles. Four beagles were treated with THIR (12C6+, 15 Gy) 2 weeks later (MI + THIR group), and four without THIR served as controls (MI group). Signal-averaged electrocardiography, programmed electrical stimulation, immunohistochemical analysis, and echocardiograms were performed at 1 year.


RESULTS
Filtered QRS duration was exacerbated after MI and remained unchanged for 1 year in the MI group (118 ± 1.4 ms), but significantly returned toward baseline in the MI + THIR group (109 ± 6.9 ms). Similarly, root mean square voltage of the last 40 ms was exacerbated after MI, but recovered after THIR. VT/VF inducibility decreased to 25% in the MI + THIR group compared with 100% in the MI group. Immunostaining Cx43 expression in cardiac tissues significantly increased by 24-45% in the MI + THIR group. Left ventricular ejection fractions remained within the normal range in both groups.


CONCLUSIONS
A single exposure of the dog heart to12C irradiation attenuated vulnerability to ventricular arrhythmia after the induction of MI for at least 1 year through the modulation of Cx43 expression.
Department of Cardiovascular Medicine, Tokai University, Isehara, Japan.
Mari
M
Amino
Department of Cardiovascular Medicine, Tokai University, Isehara, Japan.
Koichiro
K
Yoshioka
National Institute of Radiological Sciences, Chiba, Japan.
Yoshiya
Y
Furusawa
Support Center for Medical Research and Education, Tokai University, Shimokasuya, Japan.
Sachie
S
Tanaka
Support Center for Medical Research and Education, Tokai University, Shimokasuya, Japan.
Noboru
N
Kawabe
Department of Cardiovascular Medicine, Tokai University, Isehara, Japan.
Tadashi
T
Hashida
Radiation Biology Team, RIKEN, Saitama, Japan.
Teruyo
T
Tsukada
Radiation Biology Team, RIKEN, Saitama, Japan.
Masako
M
Izumi
Department of Critical Care and Medicine, Tokai University, Isehara, Japan.
Sadaki
S
Inokuchi
Department of Cardiovascular Medicine, Tokai University, Isehara, Japan.
Teruhisa
T
Tanabe
Department of Cardiovascular Medicine, Tokai University, Isehara, Japan.
Yuji
Y
Ikari
D000818:Animals; D004285:Dogs; D063193:Heavy Ion Radiotherapy / Q000379:methods*; D008137:Longitudinal Studies; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000532:radiotherapy*; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*
animal studies; fatal ventricular tachyarrhythmias; heavy ion irradiation; myocardial infarction