An in vivo rabbit joint injury model to measure trauma-induced coagulopathy and the effect of timing of administration of ketotifen fumarate on posttraumatic joint contracture

Abstract

Objectives: Using a rabbit in vivo joint injury model, the primary objective of the study was to determine if a relationship exists between earlier time to initiation of ketotifen fumarate (KF) treatment and posttraumatic joint contracture (PTJC) reduction. The secondary objective was to determine if a coagulation response could be detected with serial thrombelastography (TEG) analysis following acute trauma in this model. Methods: PTJC of the knee were created in 25 skeletally mature, New Zealand White rabbits. Five groups of 5 animals were studied: a control group that received twice daily subcutaneous injections of normal saline and 4 treatment groups that received twice daily subcutaneous injections of KF (0.5mg/kg) starting immediately, 1-, 2-, and 4-weeks post-injury. After 8 weeks of immobilization, flexion contractures were measured biomechanically. Serial TEG analysis was performed on the control group animals pre-injury and weekly post-injury. Results: The average joint contracture in the Control Group (43.1°±16.2°) was higher than all KF treatment groups; however, the differences were not statistically significant. The average joint contracture was lowest in the 2-week post-injury treatment group (29.4°±12.1°), although not statistically significant compared to the other treatment groups. Serial TEG analysis demonstrated significantly higher mean maximal amplitude (maximal amplitude=68.9±1.7mm; P