80. Lymphatic Preconditioning: Novel Investigation Of A “Lymphatic Delay Phenomenon”

Abstract

Background: The vascular delay phenomenon is a well-described concept of flap physiology with many clinical applications used to increase flap viability. The approach employs a staged surgical procedure with selective partial disruption of the flap’s blood supply to increase the robustness of the remaining blood supply, followed by interval flap transfer 7-10 days later. While this vascular delay phenomenon has been thoroughly studied, no investigation has been performed to determine if a similar “delay phenomenon” exists for lymphatic vessels. Lymphedema frequently occurs following injury of lymphatics during lymph node dissection. The purpose of this study was to evaluate whether lymphatic preconditioning with staged disruption of lymphatics can be protective against lymphedema.

Methods: The standard murine tail lymphedema model was utilized which involves creating a 3 mm circumferential skin excision by the base of the tail and surgically clipping two lymphatics. This standard model was used for a control (Group 1, Control A, n=6). A second control (Group 2, Control B, n=5) had 3 mm circumferential skin excision, one tail lymphatic clipped at that level, and an immediate second hemi-circumferential skin excision on the more proximal tail with disruption of the other remaining lymphatic. Group 3 (experimental lymphatic preconditioning, n=6), had a 3 mm full thickness skin excision by the base of the tail, disruption of one tail lymphatic at that level (leaving one lymphatic vessel intact) followed by staged hemi-circumferential skin excision with disruption of the remaining lymphatic vessel 7 days later. Tail volume was assessed with tail measurements using the truncated cone equation. Immunohistochemistry and histology was sent.

Results: Group 3 (experimental lymphatic preconditioning) had a change in tail volume of 79.1 mm3 compared to Group 1 (Control A) 154.6 mm3 (p=0.03) and Group 2 (Control B) 126.6 mm3 (p=0.05) at 28 days post-lymphatic injury.

Conclusion: Mice that underwent lymphatic preconditioning with partial lymphatic injury followed by staged completion of lymphatic disruption 7 days later exhibited less tail swelling. This study demonstrates evidence for a novel concept of “lymphatic delay phenomenon” parallel to the well-known vascular delay phenomenon. Lymphatic preconditioning has potential translational clinical applications for protective effects to minimize lymphatic dysfunction.