Carbon Monoxide Preservation of Vascularized Composite Grafts

The objective is development of a safe, effective delivery device for carbon monoxide (CO) for preservation of vascularized composite tissues for longer periods than currently possible. CO has previously demonstrated significant benefits for organ preservation in small animal models, however, there were safety issues that impeded translation to the clinic. The immediate objectives in this Phase I feasibility proposal are construction of a CO releasing device prototype in collaboration with Lorenz Meinel, University of Wurzburg, and demonstration of effectiveness in a rat hind limb model. Expert surgeons from Johns Hopkins University will supervise limb procurement methods. The CO releasing devices will be placed in bags of organ preservation solution and activated prior to flushing and preservation of rat hind limbs. Our objectives will be addressed in three tasks:In Task 1 construction and preliminary evaluation of a therapeutic device designed to deliver 40 M CO will be performed. In Task 2 we will evaluate the CO releasing therapeutic device by rat limb flushing and static storage on ice. In optional Task 3 we will compare the impact of different CO concentrations on limb preservation. Evaluations will consist of skeletal muscle and vascular tissue physiology, metabolism and histology studies.