Pressure elevation slows the fibroblast response to wound healing

ObjectiveChronic venous insufficiency and venous ulceration are consequences of elevated pressure within affected limbs. We hypothesized that wounded cells maintained at different atmospheric pressures heal at different rates and that pressure would adversely affect the processes necessary for wound healing.MethodsWe have developed an in vitro model that replicates venous hypertension in a unique pressurized incubator using neonatal fibroblasts. Neonatal fibroblasts grown to confluence were wounded with a standardized linear incision and then placed in a unique pressure incubator at atmospheric pressure, atmospheric pressure plus 30 mm Hg, atmospheric pressure plus 60 mm Hg, and atmospheric pressure plus 120 mm Hg. Cells were observed daily until complete healing of the wound occurred. Twelve to 18 hours after wounding, proliferating cell nuclear antigen analysis was done by immunocytochemistry.ResultsWounds at atmospheric pressure plus 30 mm Hg were healed by day 3, those at atmospheric pressure plus 60 mm Hg by day 4, and those grown at atmospheric pressure plus 120 mm Hg took ≥4 days for complete healing. Significantly less proliferating cell nuclear antigen activity was present in cells grown at atmospheric pressure plus 60 mm Hg (P < .0001) and atmospheric pressure plus 120 mm Hg (P < .02). Wound edge fluorescence analysis demonstrated less fluorescence in each group compared with atmospheric pressure.ConclusionsIn this model of wound healing under pressure, neonatal fibroblasts grown to confluence and given a standardized wound displayed characteristics consistent with delayed healing. Elevated pressure has a role in the delayed migration and proliferation seen in this model.Clinical RelevanceThe elevated pressure in patients with venous insufficiency causes their wounds to heal less quickly. Understanding and quantifying the physiology and role of elevated tissue pressure due to venous hypertension will lead to a better understanding of wound healing in these patients