PB0790 - Pediatric Swine Model of Escherichia coli Sepsis - Induced Disseminated Intravascular Coagulation (DIC) and Multiple Organ Dysfunction Syndrome (MODS)

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

AS

Arun Saini, MD

Assistant Professor
Baylor College of Medicine
Houston, Texas, United States
CV

Caitlin Vonderohe

Instructor
Baylor College of Medicine/USDA/Agricultural Research Service, Children's Nutrition Research Center
Houston, Texas, United States
JM

Juan Marini

Associate Professor
Baylor College of Medicine/Texas Children's Hospital
Houston, Texas, United States
BS

Barbara Stoll

Instructor
Baylor College of Medicine/USDA/Agricultural Research Service, Children's Nutrition Research Center
Houston, Texas, United States
ID

Inka Didelija

Research Scientist
Baylor College of Medicine/USDA/Agricultural Research Service, Children's Nutrition Research Center
Houston, Texas, United States
MM

Marina Martinez-Vargas

Research Scientist
Baylor College of Medicine/Center for Translational Research on Inflammatory Diseases
Houston, Texas, United States
DS

Deepika Subramanyam

Research Scientist
Baylor College of Medicine/Center for Translational Research on Inflammatory Diseases
Houston, Texas, United States
SR

Stefanie Rivera

Research Scientist
Baylor College of Medicine/Center for Translational Research on Inflammatory Diseases
Houston, Texas, United States
VV

Vinod Vijayan

Associate Professor
Baylor College of Medicine/Center for Translational Research on Inflammatory Diseases
Houston, Texas, United States
Miguel A. Cruz, PhD

Professor
Baylor College of Medicine
Houston, Texas, United States

Presenting Author(s)

Trung C. Nguyen, MD

Associate Professor
Baylor College of Medicine/Texas Children's Hospital
Houston, Texas, United States

Background: Sepsis-induced DIC is associated with a high mortality. Currently, no therapy exists for sepsis and/or DIC other than supportive care. We previously established a swine model of Staphylococcus aureus sepsis-induced coagulopathy. Understanding the host-pathogen interaction in gram positive vs negative bacterial sepsis will help with developing therapeutics.

Aims: To establish a swine model of E coli-sepsis-induced DIC/MODS.

Methods: Eight 4-week old piglets were implanted with jugular and carotid catheters and a telemetry device in a femoral artery for continuous hemodynamic monitoring. Four days later each piglets was injected intravenously with human pathogenic E. coli with 8 different doses ranging from 0.5e5 to 3e8 CFU/kg. Fluid resuscitation was given for heart rate > 50% or mean arterial blood pressure < 30% from baseline. Platelet counts, serum alanine transaminase (AST), creatinine (sCr), and fibrin polymerization assay were done were done at pre-, and 24, 30, 48 or 70h post-E. coli inoculation or when predetermined criteria for early euthanasia was reached. Necropsies were performed.

Results: Two piglets met early euthanasia criteria at 48 and 60h, and 6 piglets were analyzed through 70h. The piglet that received 3e8 CFU/kg E coli dose developed DIC and MODS, whereas the others did not. By 48h, this piglet’s platelet counts decreased by 95% from baseline, AST and sCr increased 7.5 and 13 folds respectively. Histopathologic evaluation reveals disseminated microvascular thrombi, necrosis, hemorrhage, and infarction of the renal and hepatic parenchyma. Fibrin polymerization assays in all 8 piglets showed significant increase in fibrin clot formation potential after E coli inoculation.

Conclusion(s): We identified a dose of a human pathogenic E coli strain that promoted sepsis-induced DIC/MODS by 48h in our swine model. Further characterization of this model is ongoing with the aim of having a pathologically and hemodynamically relevant swine E coli sepsis model to study DIC/MODS and evaluate potential therapeutic targets.