Researcher's guide to preclinical animal models of acute extremity compartment syndrome

Acute extremity compartment syndrome (CS) is a serious medical complication triggered by factors such as trauma, vascular injury, or prolonged compression, resulting in elevated intracompartmental pressure (ICP) and tissue ischemia. Diagnosis remains challenging, mainly relying on the subjective evaluation of clinical symptoms. Different animal models have been used to study pathophysiology and evaluate diagnostic and therapeutic approaches. The aim of this review is to summarize and compare different animal CS models to provide insight for the development of more authentic and clinically relevant CS model. A comprehensive search of two databases was conducted. English-language animal studies focusing on CS were included. Human studies, non-acute extremity CS, and review papers were excluded. Data extraction and analysis focused on animal species, CS models, and clinically relevant assessment methods of CS. After screening, 90 studies met the inclusion criteria. Small animal (n=36, 40%) and canine models (n=31, 34.4%) were the most used animal species. A fluid infusion model (n=48, 53.3%) was the predominant induction method, followed by the ischemia-reperfusion (n=29, 32.2%) and the internal/external mechanical pressure models. Five studies used a combination CS model to achieve a more comprehensive representation of the clinical pathophysiology. Various diagnostic modalities were employed; ICP measurement (n=74, 82.2%) and evaluation of tissue oxygenation (n=10, 11.1%) were the most frequent device-based assessments. Biomarkers assessing muscle cell damage (n=15, 16.7%), antioxidant status (n=18, 20%) and inflammation (n=16, 17.8%) were analyzed as well as physical examination (n=12, 13.3%) and neuromuscular testing (n=10, 11.1%). There are a variety of validated animal species models, which can be considered depending on the research objectives. This review helps researchers evaluate model strengths and drawbacks before deciding on an experimental design.