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Technologies for Monitoring and Performing Resuscitation Primary Sponsor: National Heart, Lung, and Blood Institute Deadline: 1/1/2004 KEYWORDS This Program Announcement expires on January 2004 unless reissued. PA NUMBER: PA-01-059 PURPOSE This announcement is to encourage small businesses to participate in the research and development of new approaches, tools, methods, devices, and biomaterials to provide bioengineering-based methodologies for monitoring and performing resuscitation. Ultimately, the goal of this program is to reduce morbidity and mortality from circulatory, hypoxemic or traumatic arrest. For this purpose, this announcement is interested in fostering better systems and methods for out-of- hospital and basic resuscitation research that 1) enables monitoring of genetic, molecular, biochemical, physical or metabolic derangements associated with circulatory, hypoxemic, or traumatic arrest; and 2) elucidates the unique pathophysiology of irreversible injury following multiple organ or whole-body ischemia and reperfusion, Applications should address critical cardiac, vascular, pulmonary, or hematologic and/or surgical strategies and propose research that will significantly improve clinical outcomes of resuscitation efforts. Research plans should emphasize specialties such as medicine, surgery, imaging, computer science, bioengineering and materials science, chemistry and physics. This program will use the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) funding mechanisms. Because the length of time and cost of research involving advanced technology projects may exceed that normally awarded for SBIR/STTR grants, the National Heart, Lung, and Blood Institute (NHLBI) will allow well justified Phase I applications with a project period of up to two years and a budget not to exceed, including fixed fees, $150,000 per year total costs (maximum of $300,000 total costs for 2 years). Phase II applications in response to this Program Announcement (PA) will only be accepted as competing continuations of previously funded National Institutes of Health (NIH) Phase I SBIR/STTR awards. The previously funded Phase I award need not have been awarded under this PA but the Phase II proposal must be a logical extension of the Phase I research. The NHLBI will consider Phase II projects with a project period up to three years and a budget not to exceed $500,000 per year total costs, including fixed fees. This PA must be read in conjunction with the current calendar year publication of the Omnibus Solicitation of the Public Health Service for Small Business Innovation Research Grant Applications, and the Omnibus Solicitation of the National Institutes of Health for Small Business Technology Transfer Grant Applications: http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf. All of the instructions within the Omnibus Solicitations apply with the following exceptions: o Opportunity for two years of Phase I support with a budget not to exceed $150,000 in total costs, including fixed fees, per year; o Opportunity for three years of Phase II support with a budget not to exceed $500,000 in total costs, including fixed fees, per year. RESEARCH OBJECTIVES For the purpose of this solicitation resuscitation research will include the population of patients who collapse as a consequence of sudden circulatory, hypoxemic, or traumatic arrest. Circulatory, hypoxemic or traumatic arrest is a significant public health problem cutting across age, race, and gender. It often occurs without warning in persons who are healthy prior to their collapse. The national estimated mortality for all cause arrest is 350,000 lives per year, with economic costs for trauma related injuries estimated at over $400 billion dollars per year, in productive life years. In contrast to most problems in cardiovascular medicine, current death rates have not improved significantly despite scientific advances throughout medicine. In recognition of this public health burden, in June 2000, the NHLBI led a multi-agency conference entitled, "Post-Resuscitative and Initial Utility in Life Saving Efforts" (PULSE) co-sponsored by the National Institute of Child Health and Human Development (NICHD), the National Institute of General Medical Sciences (NIGMS), the National Institute of Neurological Disorders and Stroke (NINDS), of the National Institutes of Health (NIH), the Food and Drug Administration (FDA), and the Department of Defense (DOD). Nearly 200 conference participants, from the domestic and international scientific and practice community, spanning basic, applied, and trauma science expertise, met for two and a half days to identify obstacles and to forge a research agenda that would save lives and restore arrest victims to their pre-event neurologic and physical condition. Conference participants concluded new therapies and technologies to increase survival outcomes in resuscitation are realistic and should be fostered. A key obstacle for contemporary treatment strategies is the acutely limited time window for effective treatment. Beyond ten minutes after victim collapse, the likelihood of complete physical and neurologic recovery with conventional resuscitation is very low and overall survival for arrest victims is less than ten percent. Extension of therapeutic time windows and support of critical physiologic functions provides an opportunity to expand strategies for the treatment of arrest syndromes and for dramatic improvement in survival. The need to stimulate the development of enabling technology and new scientific avenues to expand basic and applied resuscitation research was a recurring theme throughout the Workshop deliberations. It became a key recommendation of the conference, and is the basis for this solicitation. The theoretical basis for cardiopulmonary resuscitation (CPR) practice, closed chest compressions and ventilation, was established in the 1960's. The fundamental strategies for CPR have not changed since these original concepts emerged and there is a paucity of contemporary CPR research. Outcomes in trauma related battlefield statistics have not improved significantly since the Civil War. Recognition of ventricular fibrillation, a common cause of circulatory arrest, and the efficacy of cardioversion in restoration of normal conduction and spontaneous circulation occurred in the 1940's. Despite numerous advances in the identification of patients at risk and the use of therapeutic interventions including drugs and devices the outcome of resuscitation efforts for arrest victims remains poor. Even with contemporary use of the automated external defibrillator to enhance successful patient discharge rates in controlled studies remains less than twenty percent. Survival is significantly lower if complete neurologic recovery is included. Existing strategies known to restore circulation, shorten ischemia, and save lives should be refined to encourage and facilitate rapid, widespread and effective out-of-hospital application and are encouraged by this announcement. Current investigations are limited by underutilization of systems correlations and understanding of interrelated factors which contribute to irreversible cellular, vascular and organ damage in arrest states. Expansion of basic and applied research with a goal of identifying new therapies to minimize or tolerate whole-body ischemic insults holds promise for a dramatic improvement in survival rates. Scientific evidence exists to support assumptions that metabolic modulation of cellular and tissue systems could improve survival. New therapeutic interventions are likely to be derived from an understanding of cellular biology and gene expression that provide protection or tolerance to ischemia, reperfusion injury and other derangements of inadequate perfusion. A critical obstacle to improve survival, particularly for out-of-hospital arrest, is the lack of methods and systems to identify, monitor, and trend physiologic ( biochemical, metabolic or cellular) parameters. Noninvasive or minimally invasive devices to be applied in the field to detect blood and tissue oxygen, carbon dioxide levels, pH, blood pressure, and assess vital organ perfusion are desperately needed. These devices need to be interrelated and should not impede resuscitation efforts. Such technology would facilitate research, identify critical markers, or trends of these markers, and provide critical baselines for monitoring and assessment of arrests victim during resuscitation efforts. Rapid out-of-hospital application of a percutaneous, or noninvasive continuous flow circulatory support system with the ability to administer fluids and deliver medications can be vital to survival of arrest victims. Enhancement of survival outcomes following resuscitation and development and piloting of innovative strategies which may, directly or indirectly, effect this outcome is the primary goal zf this announcement. The primary potential target is the control and/or alleviation of whole- body ischemia and reperfusion injury before, during, and following resuscitation. Several factors contribute to the eventual demise of heart, lung or vascular cells, including oxidant stress, calcium overload, osmotic stress, energy depletion, and inflammation. New therapeutic interventions may focus on addressing mechanisms of regional or whole-body ischemia and reperfusion to improve survival. Hypothermia successfully preserves cells, tissue, organs and organ systems in a variety of settings, however, there are hypothermia-related complications, including changes in electrical stability of the heart, clotting factors, blood chemistries and tissue oxygen that need further investigation. Research projects to evaluate novel methods to induce controlled hypothermia in the field or during resuscitation efforts, offer novel opportunities to increase the functional time window in resuscitation victims and significantly improve survival. Investigations in hibernation, birth, and shock, that are associated with sudden profound changes in circulation, metabolism, and basal physiologic processes may provide insight for new therapeutic or protective strategies for complete physiologic and neurocognitive recovery. Trauma arrest victims provide unique challenges and opportunities for resuscitation research. Thrombosis and hemorrhage control are critical in the care of trauma victims. Resuscitation can be successful only if hemostasis is achieved and delivery of critical substrate is adequately restored. The identification, development, and testing of an optimal resuscitation fluid, which can prolong tissue viability, whether a temporary or long-term substitute for blood derived products, would be a boon for trauma resuscitation survival outcomes. Innovative strategies or systems to provide rapid vascular access and appropriate replacement fluid delivery will be a major advance in reducing trauma related deaths. Noninvasive or minimally invasive imaging techniques providing rapid assessment of multiple vital organ function, volume status, or cellular or organ perfusion rates during resuscitation efforts is critical to assess patient status and would provide timely feedback to implement and assess appropriate treatment. Unwitnessed arrest or collapse in a public facility presents another critical resuscitation challenges. Instantaneous interactive communications systems, such as global positioning technology, is needed as a rapid alert system for paramedical personnel and to provide bystanders with instructions for initiation of life-saving resuscitation measures. This PA seeks to encourage potential applicants to take full advantage of the SBIR/STTR program mechanism for multi-disciplinary research projects that develop monitoring systems and approaches to perform resuscitation that are safe and effective for use in humans. In the pre-clinical or clinical development phases, collaborations with approved animal facilities and healthcare organizations may be required. Research proposals should focus on improving out-of-hospital resuscitation, but the need to evaluate specific technologies and approaches in the clinic during design development is recognized. This program seeks innovative projects to provide new capabilities in systems and methods. Projects that offer only incremental advances of existing in-hospital technologies will not be responsive to this PA. Examples of topics the research and clinical communities have identified are listed below: however this program announcement is not limited to these examples and is open to all relevant, meritorious research ideas: o Develop ultra fast methods for recognition and identification of patient collapse and location. o Design to improve defibrillator technology. o Develop enabling technologies for research of whole body ischemia and reperfusion injury in appropriate animals models and humans. o Develop methods to augment rapid delivery and transfer of oxygen to cells, tissues and organs. o Develop methods for rapid functional restoration of circulation, both neurologic and cardiovascular, during cardiac, hypoxemic and/or traumatic arrest. o Develop methods for rapid vascular access and delivery of medications and resuscitation fluids, either traditional or novel synthetic preparations o Develop materials and methods for rapid induction of controlled hypothermia o Develop alternative methods to traditional CPR to maintain vital organ blood flow and nutrient delivery during cardiac, hypoxemic, and/or traumatic arrest. o Develop biosensors, using natural and synthetic substrates, for acquisition and monitoring of critical vital organ function, (e.g. cardiac, neurologic, cellular and tissue oxygen levels). o Develop methods to rapidly identify and implement hemostasis in trauma victims. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Heart and Vascular Caroline C. Webb, MSN, CCRN Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute Rockledge II, Room 9174, MSC 7940 Bethesda, MD 20892-7940 Telephone: (301) 435-0515 FAX: (301) 480-1336 Email: webbca@nhlbi.nih.gov Pulmonary Ms. Ann Rothgeb Division of Lung Diseases National Heart, Lung, and Blood Institute Rockledge II, Room 101114, MSC 7952 Bethesda, MD 20892-7952 Telephone: (301) 435-0202 FAX: (301) 480-3557 Email: rothgeba@nih.gov Hematology and Blood Resources Henry Chang, M.D. Division of Blood Diseases and Resources Rockledge II, Room 10170 MSC 7950 Bethesda, MD 20892-7950 Telephone: (301) 435-0067 FAX: (301) 480-1060 Email: changh@nih.gov Epidemiology Lawton Cooper, M.D. Division of Epidemiology and Clinical Application Rockledge II, Room 8124 MSC 7936 Bethesda, MD 20892 Telephone: (301) 435-3077 FAX: (301) 480-1669 Email: cooperl@nih.gov Direct inquiries regarding fiscal matters to: Ms. Shelia Ortiz Division of Extramural Affairs Grants Operations Branch National Heart, Lung, and Blood Institute Rockledge II, Room 7154, MSC 7926 Bethesda, MD 20892-7926 Telephone: (301) 435-0166 FAX: (301) 480-3310 Email: Ortizs@nih.gov National Heart, Lung, and Blood Institute (http://www.nhlbi.nih.gov)