A rodent method of peripheral lymphedema

A reliable, inexpensive counterpart of human lymphedema has been notoriously difficult to reproduce thereby stifling basic and clinical research on this neglected condition. Refining a method initially proposed by Kanter et al (Plast. Reconstr. Surg. 85(4):573, 1990), we carried out microsurgical ablation of regional groin lymphatics using excision guided by visual blue dye lymphography and/or targeted single dose irradiation (4500 rads) to a medium field encompassing the groin in an attempt to produce sustained hindlimb lymphedema. Forty-five rats (Wistar-fuzzy) underwent either groin nodal/lymphatic excision (S) or irradiation (R) alone or combined S followed by R or R followed by S and observations made for >30 days thereafter. Hindlimb volumes were determined serially using the truncated cone formula based on multiple circumferences at standardized intervals along the affected limb and compared to the contralateral control limb Impaired lymphatic drainage was assessed in selected rats from each group by lymphangioscintigraphy (LAS). Results: (Mean±SEM) Hindlimb Volume (% Increase) GROUP n 7-11 17-21 >30 R only 5 5.5±3.0 7.5±3.2 -0.6±1.3 S only 5 54.4±18.0 35.1±13.3 11.5±3.2 R then S 10 84.5±11.1 54.9±6.9 54.9±6.9 S then R 15 101.3±9.3 59.4±11.8 55.9±8.0 S or R alone produced only transient or mild hindlimb edema. In contrast, S-R or R-S induced sustained lymphedema as documented by continued increased limb volume and a deranged LAS. Both combined groups, however, exhibited substantial (13-20%) early mortality likely from radiation toxicity. This relatively inexpensive rodent model of secondary lymphedema reliably simulates the clinical condition within 30 days and should facilitate standardized testing of therapeutic/preventive protocols and basic research into the pathophysiology of this disorder.