Biological Cardiac Tissue Effects of High-Energy Heavy Ions – Investigation for Myocardial Ablation

• Published in: Scientific reports 2019-03, Vol.9 (1), p.5000, Article 5000
• Main Authors: Rapp, Felicitas, Simoniello, Palma, Wiedemann, Julia, Bahrami, Karola, Grünebaum, Valeria, Ktitareva, Svetlana, Durante, Marco, Lugenbiel, P., Thomas, D., Lehmann, H. Immo, Packer, Douglas L., Graeff, Christian, Fournier, Claudia
• Format: Article
• Language: English
• Subjects: 13/1; 13/2; 13/51; 14/63; 631/1647/767/1657; 639/766/419/1131; 692/4019; 82/80; Animals; Arrhythmia; Arrhythmias, Cardiac - pathology; Arrhythmias, Cardiac - radiotherapy; Biological effects; Cardiomyocytes; Catheter Ablation - adverse effects; Catheters; Charged particles; Conduction; Coronary artery disease; Energy; Feasibility studies; Fibers; Fibrosis; Heart; Heart - radiation effects; Heart diseases; Heart Rate - radiation effects; Heavy Ions - adverse effects; Hemorrhage; Humanities and Social Sciences; Humans; Inactivation; Ions; Medical instruments; multidisciplinary; Myocardium - pathology; Myocytes, Cardiac - pathology; Myocytes, Cardiac - radiation effects; Oncology; Polarity; Radiation, Nonionizing - adverse effects; Radiosurgery; Radiosurgery - adverse effects; Science; Science (multidisciplinary); Stereotaxic Techniques - trends; Swine; Tissues; X-Ray Therapy - adverse effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-41314-x

Noninvasive X-ray stereotactic treatment is considered a promising alternative to catheter ablation in patients affected by severe heart arrhythmia. High-energy heavy ions can deliver high radiation doses in small targets with reduced damage to the normal tissue compared to conventional X-rays. For this reason, charged particle therapy, widely used in oncology, can be a powerful tool for radiosurgery in cardiac diseases. We have recently performed a feasibility study in a swine model using high doses of high-energy C-ions to target specific cardiac structures. Interruption of cardiac conduction was observed in some animals. Here we report the biological effects measured in the pig heart tissue of the same animals six months after the treatment. Immunohistological analysis of the target tissue showed (1.) long-lasting vascular damage, i.e. persistent hemorrhage, loss of microvessels, and occurrence of siderophages, (2.) fibrosis and (3.) loss of polarity of targeted cardiomyocytes and wavy fibers with vacuolization. We conclude that the observed physiological changes in heart function are produced by radiation-induced fibrosis and cardiomyocyte functional inactivation. No effects were observed in the normal tissue traversed by the particle beam, suggesting that charged particles have the potential to produce ablation of specific heart targets with minimal side effects.