Impact of treadmill exercise after lymph node dissection followed by radiotherapy in a rodent model

Abstract

Background and Purpose: Lymphedema is a chronic condition caused by radiotherapy and surgery, and exercise has been reported to have a positive effect on this condition. However, exercise-induced changes in the lymphatic system and skin after lymph node dissection and radiotherapy are not well established. Therefore, the aim of this study was to examine alterations in lymphatic drainage pathway, skin thickness, and the extent of fibrosis in rats with lymph node dissection and radiotherapy after treadmill exercise. Materials and Methods: 12 Sprague-Dawley rats were divided into exercise and control groups of 6 rats each, and lymphedema was induced by popliteal and inguinal lymph node dissection followed by irradiation. The exercise group underwent treadmill exercise for 30 minutes per day, five days a week for four weeks. The hind limbs were imaged using indocyanine green (ICG) lymphography every other week during the exercise period to visualize lymphatic function, while ankle thickness was measured weekly to assess changes in the extent of swelling. Histopathological analysis was conducted at the end of the exercise period to examine dermal thickness, lymphatic vessel density, and the degree of fibrosis. Results: Exercise after surgery and irradiation resulted in improved lymphatic fluid retention. At week 3, the ICG lymphography showed that the group that performed exercise had a higher occurrence of linear and splash patterns. In addition, Ankle thickness was consistently lower in the exercise group, but there was exclusively significant difference between exercise and control groups at week 4 (p= .016). The group that underwent exercise showed a thinner epidermis and dermis compared to the control group (p = .041 and .002 each), as well as a lower percentage of collagen area (p = .002) and a higher lymph vessel density (p = .002). Conclusion: The results show that exercise may have a positive effect on the pathology of the lymphatic system after treatment that may induce lymphedema, including surgery and radiotherapy.