Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.
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2013-09-10
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INTRODUCTION: Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. METHODS: Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. RESULTS: Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. CONCLUSIONS: These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection.
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Wilson, Joel, David Higgins, Haley Hutting, Natalie Serkova, Christine Baird, Ludmila Khailova, Kelly Queensland, Zung Vu Tran, et al. (2013). Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis. Crit Care, 17(5). p. R195. 10.1186/cc12889 Retrieved from https://hdl.handle.net/10161/12991.
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Paul Edmund Wischmeyer
Paul Wischmeyer M.D., EDIC, FASPEN, FCCM is a nutrition, exercise, critical care, and perioperative physician-researcher who specializes in enhancing preparation and recovery from surgery, critical care and COVID-19. He serves as a Tenured Professor of Anesthesiology and Surgery at Duke. He also serves as the Associate Vice Chair for Clinical Research in the Dept. of Anesthesiology and Director of the TPN/Nutrition Team at Duke. Dr. Wischmeyer earned his medical degree with honors at The University of Chicago Pritzker School of Medicine, where he was elected into the honor society of Alpha Omega Alpha for outstanding academic achievement. He completed his pediatric internship at University of Colorado Children’s Hospital and his anesthesiology/critical care residency training at the University of Chicago. He also completed a Clinical Pharmacology fellowship and the NIH K30 Clinical Research Scientist Training Program while at University of Chicago.
Dr. Wischmeyer’s clinical and research focus is in critical care, perioperative care exercise, and nutrition to help patients prepare and recover from illness and surgery. His research interests include surgical and ICU nutrition and exercise rehabilitation; role of parenteral, enteral, and oral nutrition to improve patient outcomes; perioperative optimization; post-illness muscle mass and functional recovery; and probiotics/microbiome. His research interests have also recently been focused on COVID-19 research into COVID-19 metabolism, role of probiotics in COVID19 prevention and treatment, and exercise and nutrition programs to recover from COVID-19 and Long COVID-19. Dr. Wischmeyer’s research group has been awarded multiple NIH, DOD, and other peer reviewed grants to perform research ranging from basic mechanistic cell work to large-scale multi-center clinical trials in the fields of critical care, perioperative medicine, nutrition, illness metabolism, microbiome/probiotics, and exercise interventions to improve functional outcomes. For his research work and clinical work, Dr. Wischmeyer has received numerous awards from national and international societies including, The Jeffrey Silverstein Award and Memorial Lecture for Humanism in Medicine from the American Delirium Society, The John M. Kinney Award for the most significant contribution to field of general nutrition, the Stanley Dudrick Research Scholar Award by the American Society for Parenteral and Enteral Nutrition and The Lifetime Achievement Award of the International Parenteral Nutrition Society (IPENEMA) for significant contributions to the field of nutrition. Dr. Wischmeyer has over 200 peer-reviewed publications in critical care, anesthesiology, and nutrition, including in the New England Journal of Medicine. Finally, he has been an invited speaker at numerous national and international medical meetings delivering over 900 invited presentations over his career. He has an H-index of 73 with over 16,500 citations to his work, including 1 publication with > 1000 citations and 55 publications with > 100 citations. He is also the founder and director of the Duke Online Clinical Nutrition Fellowship, an international fellowship to provide clinical nutrition training to healthcare providers worldwide, as well as unique scholarship opportunities for healthcare providers in developing nations.
Dr. Wischmeyer passion for helping patients recover from illness and surgery arises from his personal experiences as both doctor and patient in the ICU. Dr. Wischmeyer has undergone over 27 major surgeries and personally experienced multiple ICU stays due to a childhood GI illness that took more than half of his intestinal tract. Thus, preparation for surgery/critical care and recovery from illness are a way of life for Dr. Wischmeyer that he is passionate about teaching his patients and other caregivers worldwide.
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