Plenary: Next Frontier, Sunday
Plenary: Next Frontier
Presentation Authors: Alexander Earhart, Nicholas Staten, Alana Desai, Henry Lai, Ramakrishna Venkatesh, Carlos Puyo*, St. Louis, MO
Introduction: Bladder instrumentation by a foreign body (foley catheter) induces inflammation mediated by neutrophil cells. Damage associated molecular patterns (DAMPs); in particular toll-like receptor 9 (TLR9) activate neutrophil production of cytokines. We hypothesized that activation of toll-like receptor 9 (TLR9) induced by necrotic cells may lead to tissue damage.
Methods: After approval by the Animal Care Committee at Washington University in St. Louis, we studied 5 domestic swine receiving a foley catheter. Urine samples were collected over 6 hours. Following cell counts urine neutrophils were labeled with monoclonal antibodies. IL-1β, IL-6, IL-8, IL-10 and TNF-α (figure 1), TLR9, and mitochondrial DNA (mtDNA) (Figure 2), were analyzed by qPCR. Neutrophil Elastase was detected by spectrometry. Specimens from areas of direct contact (urethra, bladder neck and fundus) were stained with H&E (Figure 3). Mann-Whitney U test was performed, p<0.05 was considered significant.
Results: Foley catheter placement resulted in neutrophilia (p<0.01). Elevated cytokine transcription during the first 3 hours for IL-6, IL-8 (p<0.01), TNF-α (p<0.01), and IL-1β was evident. At 6 hours a noticeable elevation of the anti-inflammatory cytokine IL-10 appeared to reverse proinflammatory cytokine transcription. TLR9 (p<0.001) and mtDNA (p<0.05) transcription was significant. Histology of the bladder at urethra (A), bladder neck (B), and fundus (C) shows diffuse epithelial injury.
Conclusions: Cystitis induced by tissue damage is evident by 3 hours of exposure to a foley catheter resulting in elevated neutrophil cytokines, and TLR9 transcription. Therapies to ameliorate early neutrophil activation may prevent inflammation and infection
Source Of Funding: Washington University St, Louis Anesthesiology Department
World Wide Technology and The Steward Family Foundation
Washington University School of Medicine St. Louis
Carlos A. Puyo, M.D. Assistant Professor Washington University School of Medicine St. louis.
a.Undergraduate: La Salle High School
b. Graduate: Juan N. Corpas School of Medicine, Colombia
c. Postgraduate: Emory University
Harvard Medical School
As a Board Certified physician in Anesthesia and Critical Care I have developed interest in innate immunity and mucosal inflammation induced by ETT, and Foley catheters. Because the knowledge of tracheal and bladder immunity is limited, I developed a swine model in which innate immunity alterations were demonstrated. We have documented in human and swine subjects that leukocytes, cytokines, mitochondria DNA and Toll-like Receptor 9 (TLR9) are induced by cellular necrosis. However no clear mechanism(s) have been documented to explain the development of neutrophilic airway and urinary diseases such as Acute Lung Injury (ALI), Ventilator Associated Pneumonia (VAP), and urinary tract infection (UTI) intil now. My commitment to human health and my training place me in a unique position to efficiently translate our findings to clinical practice.
Selected Peer reviewed manuscripts
1. Puyo, CA, Tricomi SM, Dahms TE. Early Biochemical Markers of Inflammation in a Swine Model of Endotracheal Intubation. Anesthesiology. 2008 Jul; 109(1):88-94.
2. Puyo, CA, Dahms, TE. Innate Immunity Mediating Inflammation Secondary to
Endotracheal Intubation. JAMA Arch Otolaryngol Head Neck Surg. 2012; 138(9):854-858.
1. Alex Earhart, Nicholas Staten, Andrew Gelman, Carlos A. Puyo. Neutrophil Cytokines and TLR9 Transcription During Endotracheal Intubation in a Swine Model. IARS 2017.
2. Alexander Earhart, Nicholas Staten, Andrew Gelman, Carlos A. Puyo. Mediators of Neutrophil Activation In A Swine Model of Tracheal Injury. IARS 2017.
3. Earhart, Nicholas Staten, Alana Desai, Henry Lai, Ramakrishna Venkatesh, Carlos A. Puyo. Bladder Injury Activates Innate Immunity During Short-term Foley Catheterization in a Swine Model. American Urological Association. 2017.