Animal Models of Lymphaticovenous Anastomosis: A Systematic Review of Current Evidence and Future Directions in Translational Research.

Abstract

Lymphovenous bypass (LVB) or lymphaticovenous anastomosis (LVA) is increasingly applied, including experimental use for Alzheimer's disease via cervical lymphatic pathways. However, literature on long-term patency and failure mechanisms is scarce, and no gold standard exists for evaluating durability. Robust, reproducible LVA models are essential to advance translational research. This review maps current animal models and proposes strategies for improving reliability and mechanistic insight. A PRISMA-guided search of PubMed, Scopus, and Google Scholar identified original animal studies reporting intra- or postoperative patency using functional or structural methods. Extracted data included species, anastomosis type, assessment tools, follow-up intervals, patency rates, and histology. Of 107 records screened, 11 met criteria: rats (n = 7), rabbits (n = 1), piglets (n = 1), and canines (n = 2). Techniques were mainly end-to-end (n = 9) and end-to-side (n = 2), targeting femoral, iliolumbar, popliteal, mesenteric, cervical, and thoracic-duct outflows. Intraoperative patency was uniformly high (≥ 90%). Postoperative patency was reported in six studies, ranging from 80% to 100% at ≤ 7 days (ICG lymphography) to 67% at 1 month (canines). Histology (three studies) distinguished patent sites (smooth endothelium) from failed ones (irregular endothelium, thrombus, fibrosis). Follow-up was categorized as short-term (0-7 days), mid-term (2-4 weeks), and long-term (≥ 1 month), but standardized long-term outcomes were absent. Future models should integrate noninvasive imaging, serial long-term follow-up, and detailed histologic and molecular analysis to clarify success and failure mechanisms. Standardized methodologies will enhance translational relevance, refine surgical techniques, and inform therapies to improve LVA durability.