This application contains a four year research training program for the development of an academic career in physiology and medicine. The candidate completed an emergency medicine residency at the University of Massachusetts Medical School in 1998 and has continued to perform research, teaching and clinical duties at the university. The described training program is designed to provide the candidate with the didactic and practical experience necessary for him to become an independent investigator in the field of ischemia and reperfusion injury. The scientific aims of this investigation focus on characterizing an unidentified cardioprotective factor released from preconditioned myocardium. The PI has chosen Dr. Robert E. Carraway PhD as a mentor for this project. As director of the Peptide Core Facility at the university, Dr. Carraway has extensive experience in characterizing unidentified factors both mechanistically and compositionally. To further augment his training, the PI will meet regularly with two cardiac physiologists at his institution. The candidate's research efforts will focus on determining the mechanism by which a naloxone sensitive factor released from ischemic hearts evokes improved ischemic tolerance in myocardium and mesenteric tissue. Specific emphasis will be placed on determining: (1) the opioid receptor subtype involved in the induced protection; (2) the role of PKC and KATP, channels in the evoked ischemic tolerance; (3) the relationship between actual opioid receptor binding and cardioprotection; and (4) the role of the opioid receptor system in remote preconditioning. The combined Departments of Physiology and Emergency Medicine at the University of Massachusetts Medical School is an ideal setting for this grant and will provide Dr. Dickson with the facilities, equipment and expertise necessary to achieve the goals set forth in this proposal.