Abstract
Purpose
Compartment syndrome is a limb threatening condition. Prior research has been limited by an inability to assess functional and histologic changes in muscle over time. This study was designed to assess and quantify functional deficits and histologic changes following acute compartment syndrome of the lower limb in a novel rat model.
Method
Twenty-three male Wistar rats were trained to perform an incentive-based standard task on an optical gait tracking system. Animals were then randomized to three groups: Control (n=4), Sham (n=4) and Compartment Syndrome (CS, n=15). Control and sham animals had no elevation of intracompartmental pressure, while CS animals had elevated intracompartmental pressure to 30mmHg for 180 minutes in the anterior compartment of the left hind limb using a saline infusion technique. Following intervention, gait analysis was performed at 2hrs, 24hrs, 48hrs, 72hrs and 7days following injury. Several parameters for the injured hind limb were analyzed including: print area, print intensity, maximum contact timing, duty cycle and stance phase time. A 2-way ANOVA with Bonferroni post-hoc analysis was performed. The EDL muscle was harvested (n=17), fixed in formalin and prepared with an H&E stain. Mid-muscle sections were analyzed by a blinded senior pathologist for cell infiltration, necrosis and regeneration.
Results
Function Changes: Mean print intensity was 96.5518.7 at 48hrs for CS animals, compared to 145.538.2 in control animals and 144.9612.71 in sham animals (p<0.001). At the 2hrs, 24hrs, and 48hrs time intervals post injury the CS animals showed significant decreases in print width (p<0.001), maximum contact (p<0.001), mean print intensity (p<0.001) and stance phase (p<0.01). There were no significant differences between baseline and 72hr results for any gait parameter (p>0.05).
Histologic Changes: Cellular infiltration was noted at 24hrs, peaked at 48hrs and was still present at 7 days to a lesser degree. Necrosis began as early as 24hrs post injury and also peaked by 48hrs and returned to baseline levels by 7days. Minor regenerative changes were identified as early as 24hrs however the majority of changes were identified at 7 days post-injury.
Conclusion
Developing and evaluating animal models for the study of compartment syndrome is essential for better understanding the condition and testing new treatment modalities. Gait analysis was a reproducible means of assessing function after compartment syndrome. Animals demonstrated an antalgic gait pattern demonstrated by decreased stance phase, decreased print intensity, and increased print width, with recovery demonstrated by 72hrs post-injury. Defining the histologic changes such as necrosis, cellular infiltration and regeneration associated with compartment syndrome has allowed us to further understand the evolving pathology of compartment syndrome over time. This study facilitates the evaluation of functional and histologic testing for the evaluation of new therapeutic interventions.
