The potential of a heavy particle radiotherapy as the definitive noninvasive treatment for the life threatening ventricular tachy-arrhythmias

Patients after non-transmural myocardial infarction (MI) are known to be highly susceptible for life-threatening ventricular arrhytbmias (VT/VF). Our previous in-vivo experiments showed that targeted external heavy ion bean radiation (THIR) to the left ventricle reduced vulnerability for VT/VF in MI rabbits, however the underlying mechanisms are not known. Non-transmural MI was created in rabbits by microsphere injection into coronary arteries. THIR to the tissue (15 Gy) was carried out from the outside without open chest, 2 weeks after MI, using Heavy Ion Medical Accelerator in Chiba, Japan (HIMAC). MI rabbits were irradiated through the left chest (beam size 2 x 2 cm) using a single dose of a heavy ion beam. The hearts excised 2 weeks later were employed for high-resolution optical mapping studies. Optical signals in MI rabbits were characterized by a moderate decrease of conduction velocity (CV), whereas no remarkable change of CV after THIR+MI. Local dispersion of action potential duration (APD) was increased from 13±3.8 ms (CON, n=4) to 23±9.1 ms (MI, n=6), however THIR+MI resulted in a significant reduction to 15±5.0 ms (p<0.05 vs. MI). VTs were induced by premature stimuli in 5/6 MI heats, whereas 2/4 THIR+MI hearts. VTs in THIR+MI heart showed more organized excitation and did not transformed into VF. The ventricles after non-transmural MI have large local APD dispersion, and it may set a stage for functional reentry and its disorganization. THIR improves the electrical stability by reducing spatial inhomogeneity of repolarization. (author)