Compartment Syndrome (CS) is a condition of high tissue pressure causing ischemia damaging muscles and nerves. It is known that in highly non-compliant tissues a small fluid volume decrease can produce a large pressure drop, and thereby increase perfusion and improve circulation and oxygenation. During Phase I, we demonstrated feasibility of an innovative use of tissue ultrafiltration (UF) to reduce tissue pressure by removing interstitial and/or intracellular fluid volume, and to use the increased fluid levels of metabolites to improve diagnosis. 77'e central hypothesis is that UF catheters in muscle compartments can be used to improve functional outcome in CS, by improving diagnosis and reducing intramuscular pressure. In Phase II, bench, animal and human studies have been designed to further develop UF as a clinical tool. Patients will not be placed at higher risk of CS sequelae since UF has limited invasiveness, a history of safety as an assay tool, and does not pre-empt eventual fasciotomy should clinical signs and symptoms warrant. Our expectation is that clinical application of CSUF will provide earlier diagnosis, less morbid treatment, and will prevent sequelae of untreated CS. Expected US healthcare cost savings from the use of CSUF are $200 million per year.