Time-Dependent Efficacy of Lymphaticovenous Anastomosis in Secondary Lymphedema: A Rabbit Model Study

Secondary lymphedema remains a common complication after oncologic lymph node dissection. The optimal timing of lymphaticovenous anastomosis (LVA) is unclear due to a lack of time-dependent large-animal models. Twenty-five New Zealand White rabbits underwent popliteal-region surgery to induce secondary hind limb lymphedema. Animals received immediate LVA (n = 5) or delayed LVA at 4, 8, or 12 weeks after model induction (n = 5 per group); untreated lymphedema controls were included (n = 5). Outcomes included limb circumference/swelling rate, anastomotic patency by indocyanine green (ICG) fluorescence imaging, and histopathology/molecular markers (e.g., VEGF-C, LYVE-1). The model produced sustained hind limb swelling and molecular evidence of lymphangiogenic remodeling (e.g., increased VEGF-C and LYVE-1). Immediate LVA achieved 100% technical success with durable patency during follow-up. Delayed LVA groups demonstrated patency rates of approximately 75%-80%. Immediate intervention resulted in the greatest long-term reduction in swelling compared with delayed interventions. Mean lymphatic and venous diameters were approximately 0.6 and 0.8 mm, respectively, and mean operative time was ~55 min. This rabbit model provides a reproducible platform to evaluate time-dependent LVA efficacy. Earlier intervention yielded superior functional outcomes, while delayed LVA remained feasible and maintained reasonable patency, supporting a clinically relevant therapeutic window.