Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

• Published in: International journal of radiation oncology, biology, physics Vol. 88; no. 1; pp. 167 - 174
• Main Authors: Sridharan, Vijayalakshmi, PhD, Tripathi, Preeti, MS, Sharma, Sunil, PhD, Moros, Eduardo G., PhD, Zheng, Junying, PhD, Hauer-Jensen, Martin, MD, PhD, Boerma, Marjan, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2014
• Subjects: Animals; APOPTOSIS; Capsaicin - pharmacology; Cardiac Output - drug effects; Cardiac Output - physiology; Cardiac Output - radiation effects; Denervation - methods; Echocardiography - methods; FIBROSIS; HEART; Heart - innervation; Heart - physiopathology; Heart - radiation effects; Hematology, Oncology and Palliative Medicine; IRRADIATION; ISCHEMIA; MACROPHAGES; Macrophages - drug effects; Macrophages - radiation effects; Male; MAST CELLS; Mast Cells - drug effects; Mast Cells - physiology; Mast Cells - radiation effects; Myocardium - pathology; NEOPLASMS; NERVE CELLS; NERVES; Neurons, Afferent - drug effects; Neurons, Afferent - physiology; Neurons, Afferent - radiation effects; Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism; Nuclear Receptor Subfamily 4, Group A, Member 1 - radiation effects; Nuclear Receptor Subfamily 4, Group A, Member 2 - metabolism; Nuclear Receptor Subfamily 4, Group A, Member 2 - radiation effects; Organ Size - radiation effects; Radiation Injuries, Experimental - physiopathology; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; RATS; Rats, Sprague-Dawley; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - physiology; Sensory Receptor Cells - radiation effects
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2013.10.014

Purpose Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.