Lymphangiogenesis Is Dependent Upon The Magnitude Of Cyclic Compressive Load: Implications For Manual Lymphatic Drainage

Lymphedema is a chronic disorder characterized by a localized abnormal fluid retention, most often due to a mechanical insufficiency of the lymphatic system. The current multi-step treatment for this disorder includes lengthy sessions between client and therapist utilizing manual lymph drainage (MLD). It has been shown that MLD improves the transport capacity of lymph fluid, thereby decreasing the swelling that occurs in the affected segment of the body. MLD is a key component in the treatment for lymphedema and consists of gentle, light, and rhythmic manual techniques targeting the superficial tissues of the dermis. Although applying light manual pressure techniques (MLD) decreases localized swelling clinically, the underlying mechanisms and the influence of pressure during MLD are largely unknown. It has been hypothesized that the number of functioning lymphatics is enhanced through an increase in lymphangiogenesis following MLD, although the pressure-dependence of the treatment has not been studied in any detail. PURPOSE: To test the hypothesis that lymphatic endothelial differentiation (LYVE-1 protein abundance, determined through standard Western analysis technology) is dependent upon cyclic compressive load (CCL) magnitude. METHODS: Six Long-Evans Rats were divided into two groups, and one Tibialis Cranialis (TC) muscle was subjected to 30 minutes of CCL on three consecutive days, with contralateral TC serving as control. Group 1 received CCL of 5.5N, Group 2 received CCL of 1.4N. Twenty four hours following final CCL treatment, skin was harvested, fixed and stored for biochemical analysis. RESULTS: Three daily bouts of CCL of 5.5N resulted in greater LYVE-1 protein abundance compared to control (4.68±0.27units vs. 2.83±0.29units, p=0.01), although CCL of 1.4N had no effect (3.55±0.36units vs. 3.10±0.43units, p=0.215). CONCLUSION: Upregulation of the highly specific marker for lymph vessels, LYVE-1, is dependent upon the magnitude of applied compressive load. This indicates to us that lymphangiogenesis can be initiated through mechanosensitive pathways in the skin that are load dependent. Clinically, this illustrates the importance of proper training of therapists in the application of MLD to patients with Lymphedema.