Stereotactic Body Radiotherapy: A New Noninvasive Way to Conduct Pulmonary Artery Denervation?

Manzhen Liao¹Taoyue Yao²Yonghui Xie³Shelby Kutty⁴Jinqiao Liu²Wei Peng¹Ting Huang²Huaiyang Chen¹Haoqin Fan²Zhenghui Xiao²Qiming Liu⁵Yunbin Xiao^2*

• ¹Department of Pediatrics, Hengyang Medical College, University of South China, Hengyang, China
• ²Hunan Children's Hospital, Changsha, Hunan Province, China
• ³Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan Province, China
• ⁴School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States
• ⁵Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China

BACKGROUND Pulmonary arterial hypertension is a severe and life-threatening disease characterized by a progressive increase in pulmonary vascular resistance. Catheter-based pulmonary artery denervation (PADN) has been conducted in pulmonary arterial hypertension patients, however, if stereotactic body radiotherapy (SBRT) can become a new noninvasive way to conduct PADN has not been elucidated.METHODS A total of 12 healthy male New Zealand rabbits were digitally marked on their foreheads and randomly divided into control group (n = 6) and SBRT group (n = 6) at a ratio of 1:1 using Computer-generated random numbers. In SBRT group, rabbits were treated with a single dose of 15 Gray, then bred for a minimum of 3 months. The rabbit models of acute thromboembolic pulmonary arterial hypertension (ATEPAH) were established by injecting autologous blood clots into the femoral vein. Right ventricular function and hemodynamics were assessed by echocardiography and right heart catheterization. Pulmonary artery sympathetic nerves were evaluated by pathological staining.RESULTS The SBRT procedure was successfully performed in all six rabbits. Compared to control group, SBRT-PADN reduced pulmonary artery systolic pressure and mean pulmonary artery pressure in ATEPAH rabbits. Meanwhile, SBRT-PADN could attenuate pulmonary artery dilatation in ATEPAH rabbits. Histological examination revealed evident structural damages in sympathetic nerves of SBRT-PADN animals, including vacuolization, nuclear pyknosis and digestion chambers. No adverse events had been observed, with sparing of pulmonary artery of the intima and media were detected up to 90 days post procedure.CONCLUSIONS SBRT could destroy sympathetic nerves around pulmonary artery locally, which may represent a novel option for performing PADN. Besides, this study proveded its short-term effectiveness and safety.