1. BASIC SCIENCE HYPOXIA HYPOPERFUSION SECONDARY CELL CAMAGE PRIMARY CELL CAMAGE RESUSCITATION PERFUSION/DELIVERY VOLUME/FLOW GLOBAL HYPOXIA PERIPHERALCENTRAL CELL TO CELL COMMUNICATION ELECTRICAL COMMUNICATION CHEMICAL COMMUNICTION VITAL ORGAN DELIVERY NON-VITAL FLOW INTERRUPTION CARDIO PULMONARY NEUROLOGIC

2. Hypothermic Resuscitation Research Challenges Hypothermic Resuscitation Research Challenges George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services Definition of hypothermia How cold How long How fast When Where

3. Hypothermic Resuscitation Research Challenges Hypothermic Resuscitation Research Challenges George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services Other hypometabolic strategies Uncontrolled vs. controlled hypothermia Self-induced hypothermia - role of hibernation

4. Hypothermic Resuscitation Research Challenges Hypothermic Resuscitation Research Challenges George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services Aim of hypometabolic strategies Prevention of critical organ/system injury – “ranking” Prevention of hyperthermia

5. Hypothermic Resuscitation Research Challenges Hypothermic Resuscitation Research Challenges George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services Aim of hypometabolic strategies Role of new technologies Utilization of technologies: when, where, and by whom

6. Hypothermic Resuscitation Research Challenges Hypothermic Resuscitation Research Challenges George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services Hypometabolic strategies: clinical application Definition of outcomes Choice of relevant outcomes Role of biomarkers as a target for initiation and monitoring of interventions Identification of target population: single vs. multiple organ disorder(s)

7. Hypothermic Resuscitation Research Challenges Hypothermic Resuscitation Research Challenges George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services Hypometabolic strategies: clinical application Conduct of clinical studies: existing vs. optimal infrastructure Available models Consent: role of community, medical and professional organizations IDE/IND: when old becomes new therapy

8. Hypothermic Resuscitation Research Challenges Hypothermic Resuscitation Research Challenges George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services George Sopko, M.D., M.P.H. National Heart, Lung, and Blood Institute National Institutes of Health Department of Health and Human Services Hypometabolic strategies: clinical application Unified scientific agenda: development and implementation, timeliness, flexibility, practicality, and scientific review Funding: typically mechanistic or hypothesis driven