Compression-induced muscle injury in rats that mimics compartment syndrome in humans

Abstract

Compartment syndrome (CS) is a serious complication arising from a variety of extremity injuries and resultant swelling within the fascicles of the muscle tissue. The current standard of care for CS is fasciotomy, which relieves the intracompartmental pressure of CS but inflicts further tissue damage. The development of new techniques to treat CS include angiogenic therapy, antifibrosis treatments, and stem cell therapy, all which aim to enhance tissue regeneration and functional recovery. Current rodent models of skeletal muscle injury do not accurately mimic the complex physiological tissue damage found in CS in human patients, and large-animal models of CS cannot be used as an experimental model of human cell therapy because of the lack of immunocompromised animals. We developed a rat model of CS that mimics the sequelae of the human condition. Compression of the hindlimb of rats using neonatal blood pressure cuffs maintaining 120 to 140 mmHg for 3 hours resulted in considerable muscular, vascular, and neural damage. Histological and functional analyses documented the initial degeneration and subsequent regeneration of the muscle tissue over time. The complex muscular, vascular, and neural injury observed in this model provides an ideal platform for testing cellular, biological, and pharmacological agents for the restoration of muscle volume and function.