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The lipid mediator lysophosphatidic acid (LPA) regulates cell proliferation and enhances cell motility in vitro, both of which are important events in wound healing. To evaluate the effects of LPA in vivo, it was applied to a full-thickness wound of rat skin. LPA in micromolar concentrations, or solvent, was applied daily. Animals were killed at 1, 3, 6, and 9 days after wounding and processed for histological evaluation, including hematoxylin-eosin staining and histochemical markers for macrophage-histiocytes, proliferating cells, and capillary endothelial cells. LPA treatment accelerated wound closing and increased neoepithelial thickness. Cytological evaluation showed no evidence for a secondary inflammation-mediated injury, infection, or increased keloid formation. Whereas LPA caused only a modest dose-dependent increase in proliferating cells, a marked increase in the immigration of histiocyte-macrophage cells was observed as early as day 1. The peaks of several cytological features and immunohistological markers preceded those of the untreated side. Our data suggest that exogenously applied LPA in this model promotes healing and that macrophage-histiocytes are the primary LPA-responsive cells in vivo.

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BACKGROUND Traumatic popliteal arterial injury (TPAI) is associated with a risk of both limb loss and long-term morbidity due to prolonged ischemia and the often-associated musculoskeletal injuries. Long-term functional outcome following this injury has not been adequately studied. We evaluated patients with TPAI to determine if there was an improvement in functional outcome over time. We hypothesized that both the initial severity of ischemia and the associated injuries limited the ability of patients to improve functional outcome. METHODS Patients with TPAI for 20 years were identified. All patients had at least a 2-year follow-up. Functional outcomes were measured using the Boston University Activity Measure for Post-Acute Care to assess basic mobility (BM) and daily activity (DA). Multiple linear regression, adjusted for age, severity of injury and shock, operative complexity, associated injuries, ischemic time, and length of follow-up were used to identify predictors of functional outcome after TPAI. RESULTS A total of 214 patients were identified: 123 penetrating (57%) and 91 blunt (43%). Overall mortality was 1.9% (all in-hospital), and amputation occurred in 10%. Of the 210 survivors, follow-up was obtained in 145 patients (69%). Median follow-up was 9.2 years (interquartile range, 5.7–15.7 years). Mean Activity Measure for Post-Acute Care scores for BM and DA were 78 and 75, respectively, both signifying mild impairment (normal, >84). Multiple linear regression failed to identify increasing length of follow-up as a predictor of improved functional outcomes. Only age, lower extremity fracture, and ischemic time were identified as predictors of decreased BM and DA. CONCLUSION Increasing age, lower extremity fracture, and prolonged ischemic time worsened long-term functional outcomes. Functional outcome did not improve over time, suggesting that maximal recovery may be achieved within the first 2 years postinjury. Thus, early and effective revascularization remains the only potentially modifiable risk factor for improving functional outcomes following TPAI. LEVEL OF EVIDENCE Prognostic, level III.