Targeted Nutritional Approach to Improve Muscle Function and Physical Activity by Restoring Metabolic Deregulations During Recovery from Sepsis
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PUBLIC ABSTRACT Sepsis is a potentially life-threatening complication of an infection in critically ill patients and characterized by severe tissue breakdown in several organs, leading to long-term muscle weakness, fatigue, and reduced physical activity. Early and targeted nutritional intervention is critical to enhance recovery and rehabilitation from critical illness. The continuing high morbidity and mortality rate in sepsis illustrates the clinical and scientific need to assess the effectiveness of targeted treatments during sepsis recovery. Muscle breakdown and resulting muscle weakness can be reduced by proper nutritional care. Our rationale is that studying targeted nutritional treatment during sepsis recovery will lay the foundation to develop novel nutritional approaches for the critically ill patients to enhance recovery and rehabilitation by improved muscle mass and function. Use of clinically relevant animal models are essential to investigate the physical outcome in relation to the complex metabolic processes in muscle. Therapeutic nutritional support in a model in the pig is viewed as highly translational to humans. The proposed specific aim will be studied in an instrumented clinically relevant pig model that is recovering from an acute septic infection by Pseudomonas aeruginosa bacteria. The effects of a targeted nutritional intervention will be studied. The targeted nutritional intervention contains a mixture of essential amino acids (building blocks for muscle tissue). The proposed study in a catheterized pig model recovering from sepsis is innovative because (a) the targeted nutritional supplementation is a novel approach to attenuate tissue breakdown in sepsis and improve functional outcome and restore muscle mass and (b) it provides insights into sepsis-induced severe tissue breakdown and physical outcome. The use of innovative, stable tracer methodology to measure metabolic fluxes within and across muscle enables quantification of all metabolic endpoints. The results of the proposed study will have a positive impact by providing the basis to develop novel cost-effective nutritional approaches for patients recovering from sepsis to improve recovery and rehabilitation. It has a strong justification because of its rapid translation into clinical application. The proposed application will fit in the Topic Area: “Nutrition Optimization.” Within this Topic Area, it will address the following Area of encouragement: “development of prolonged nutrition care using oral and/or intravenous approaches including precision nutrition care following injury or illness.” It also fits the Subtopic area: “Emerging Infectious Diseases.” Especially the following Area of encouragement: “Research, development, and validation of animal models for the study of infectious diseases that clearly show the pathophysiological mechanism of the disease and provide translational data to advance drug products to human clinical trial.” Relevance to Military Health. Infections and resulting sepsis have always been a significant problem on the battlefield. When during and after World War II antibiotics became more widely available and more types of antibiotics were developed, the treatment of infections improved, but was not eliminated and sepsis remains a serious problem that needs a high level of medical treatment, while still leads to a substantial mortality and morbidity and long term rehabilitation. Therefore, there is still a critical need to identify and treat sepsis, and the long-term effects that affect many sepsis survivors. Sepsis continues to be the most expensive condition treated in acute care hospitals in the United States, and it has considerable cost for the Veterans Administration for both acute care and long-term care. Conclusion: The proposed project is relevant to public (and military) health because a clinically translational sepsis animal model will provide the physical and metabolic basis to develop a new targeted nutritional formulation to support muscle health and recovery in critically ill patients.
