Thinking Outside of the Box: A Novel Strategy to Prevent Shock Induced AKI Todd Costantini MD 11:30-11:45 Thursday, February 16 Educati<strong>on</strong>al Objectives: 1. Describe the role of tight juncti<strong>on</strong> proteins in maintaining epithelial barrier functi<strong>on</strong>. 2. Define the anti-inflammatory properties of efferent vagal nerve signaling. 3. Describe the ability of vagal nerve stimulati<strong>on</strong> to limit shock-induced acute kidney injury. C<strong>on</strong>tent Descripti<strong>on</strong>: Acute Kidney Injury (AKI) is a comm<strong>on</strong> clinical c<strong>on</strong>sequence of shock which is associated with increased morbidity and mortality in the critically ill populati<strong>on</strong>. Tubular epithelial cells play an important role in driving the inflammatory resp<strong>on</strong>se of the kidney, which is characterized by pro-inflammatory cytokine secreti<strong>on</strong> and an innate immune resp<strong>on</strong>se which further drives AKI. Vagal nerve stimulati<strong>on</strong> (VNS) has been shown to exert potent anti-inflammatory effects in multiple models of shock. We have recently dem<strong>on</strong>strated that VNS prevents intestinal barrier failure and gut inflammati<strong>on</strong> after injury through modulati<strong>on</strong> of intestinal epithelial tight juncti<strong>on</strong> proteins. We hypothesized that VNS may represent a novel strategy to limit shock-induced AKI. This series of experiments dem<strong>on</strong>strates the ability of VNS to limit kidney inflammati<strong>on</strong> and prevent injury-induced changes in epithelial tight juncti<strong>on</strong> protein expressi<strong>on</strong>. Suggested Reading: 1. Costantini TW, Bansal V, Krzyzaniak M, Putnam JG, Peters<strong>on</strong> CY, Loomis WH, Wolf P, Baird A, Eliceiri BP, Coimbra R: Vagal nerve stimulati<strong>on</strong> protects against burn-induced intestinal injury through activati<strong>on</strong> of enteric glia cells, Am J Physiol Gastrointest Liver Physiol 2010, 299:G1308-1318. 2. Tracey KJ: Physiology and immunology of the cholinergic antiinflammatory pathway, J Clin Invest 2007, 117:289-296. 3. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eat<strong>on</strong> JW, Tracey KJ: Vagus nerve stimulati<strong>on</strong> attenuates the systemic inflammatory resp<strong>on</strong>se to endotoxin, Nature 2000, 405:458-462. 4. Turner JR: Molecular basis of epithelial barrier regulati<strong>on</strong>: <str<strong>on</strong>g>from</str<strong>on</strong>g> basic mechanisms to clinical applicati<strong>on</strong>, Am J Pathol 2006, 169:1901-1909. 5. B<strong>on</strong>ventre JV, Yang L: Cellular pathophysiology of ischemic acute kidney injury, J Clin Invest 2011, 121:4210-4221. 6. Bansal V, Costantini T, Ryu SY, Peters<strong>on</strong> C, Loomis W, Putnam J, Elicieri B, Baird A, Coimbra R: Stimulating the central nervous system to prevent intestinal dysfuncti<strong>on</strong> after traumatic brain injury, J Trauma 2010, 68:1059-1064. 7. Costantini TW, Fraga G, Fortlage D, Wynn S, Fraga A, Lee J, Doucet J, Bansal V, Coimbra R: Redefining renal dysfuncti<strong>on</strong> in trauma: implementati<strong>on</strong> of the Acute Kidney Injury Network staging system, J Trauma 2009, 67:283-287. 39
Panel Discussi<strong>on</strong> Noel Gibney MB FRCP(C) 12:10-12:30 Thursday, February 16 Educati<strong>on</strong>al Objectives: To outline the pathophysiology, principles and practical aspects of fluid resuscitati<strong>on</strong> and management in the critically ill. C<strong>on</strong>tent Descripti<strong>on</strong>: Do Vasoactive Drugs and Fluids Improve Renal Perfusi<strong>on</strong>. Daniel Debacker MD. Saline is Really Bad for You. Hard to Believe. Impossible to Ignore!? John A. Kellum, MD What Blood Pressure Should We Target for Patients with AKI? Ravindra L. Mehta, MD What We Do in the OR When You're Not Looking!? Andrew Shaw, MB FRCA FCCM Water, Water, Everywhere: Sodium and Water Balance and the Injured Brain. ?Didier Payen, MD Blood Transfusi<strong>on</strong>s are Important for the Resuscitati<strong>on</strong> of the Critically Ill Patient. ?Can Ince, PhD Fluid Management in the Critically Ill: The “5B” Approach. Claudio R<strong>on</strong>co, MD Thinking Outside of the Box: A Novel Strategy to Prevent Shock Induced AKI. Raul Coimbra, MD PhD FACS SPECIAL LECTURE: ?Fluid Management in the? Critically Ill: Is the Kidney at Risk? Robert Schrier, MD 40
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