Effects of joint contracture on the contralateral unoperated limb in a rabbit knee contracture model: a biomechanical and genetic study.

Abstract

In most animal models, unoperated contralateral limbs are used as controls. However, in some experimental circumstances, the contralateral limb may represent a skewed control. The main purpose of this study was to determine if the unoperated contralateral limb could be used as a control, or if a different unoperated animal's limb should be used instead. Seventeen rabbits were divided into two groups. Group 1 rabbits (n = 12) underwent surgery on their right limbs to induce a contracture. Group 2 rabbits (n = 5) underwent no surgery. The left non-operated limbs of rabbits in group 1 were biomechanically and genetically compared to the limbs of unoperated rabbits in group 2 with the use of a validated joint measuring device and custom microarray, respectively. After 8 weeks of immobilization, there was a statistically greater flexion contracture in the unoperated contralateral limbs compared to the limbs of animals that received no surgery(8.4 ± 8.9° vs. 0 ± 0°; p-value = 0.03). When animals were remobilized for an additional 16 weeks, the significance between groups was lost (11.9 ± 21.4° vs. 8.9 ± 9.5°; p = 0.38). Similarly, there was a statistically significant increase in nine genes at 8 weeks (p < 0.001). However, at 24 weeks, only the PMCA 1 gene was statically increased (p < 0.001). In our rabbit model, the non-operated limb develops a small flexion contracture at 8 weeks. After 16 weeks of remobilization, there is no biomechanical or genetic difference between contralateral non-operated limbs and limbs of animals not undergoing any surgical intervention. Given the biomechanical and genetic findings, the contralateral non-operated limb can be used as a valid control.