Two methods of extracorporeal shock-wave therapy in a rat model of secondary lymphedema: a pilot study

Objectives To compare the effectiveness of two methods of extracorporeal shock-wave therapy (ESWT) in a rat model of forelimb lymphedema, induced by axillary lymph node dissection. Methods Sprague–Dawley rats were randomly allocated to a group that received 500 ESWT shocks only in the lymphedematous forelimb (Forelimb/ESWT) and a group that received 300 ESWT shocks in the axilla and 200 shocks in the lymphedematous forelimb (Axilla+Forelimb/ESWT). The circumferences of each limb were then measured. Immunohistochemistry for a pan-endothelial marker (cluster of differentiation [CD]31) and lymphatic vessel endothelial hyaluronan receptor-1, and western blot analysis for vascular endothelial growth factor receptor-3 (VEGFR3) and VEGF-C were performed. Results The circumferences of the limbs showed significant effects of group and time following surgery. The circumferences at the carpal joint and 2.5 cm above were smallest in the naïve limbs, larger in the Axilla+Forelimb/ESWT group, and the largest in the control group. VEGFR3 tended to be expressed at a higher level in the Axilla+Forelimb/ESWT group (1.96-fold) than in the Forelimb/ESWT group (1.20-fold) versus the opposite non-edematous forelimbs, although this difference was not statistically significant. Conclusions These data suggest that ESWT protocols have differential effects on angiogenesis and lymphangiogenesis in lymphedematous limbs.