An ovine septic shock model of live bacterial infusion.

Autor: Obonyo NG; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia. gnchafatso@gmail.com.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia. gnchafatso@gmail.com.; KEMRI-Wellcome Trust Research Programme and Initiative to Develop African Research Leaders, Kilifi, Kenya. gnchafatso@gmail.com.; Wellcome Trust Centre for Global Health Research, Imperial College London, London, UK. gnchafatso@gmail.com., Raman S; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Children's Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Paediatric Intensive Care Unit, Queensland Children's Hospital, Brisbane, QLD, Australia.; Queensland Paediatric Sepsis Program, Children's Health and Youth Network, Children's Health Queensland, Brisbane, Queensland, Australia., Suen JY; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Peters KM; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia., Phan MD; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia., Passmore MR; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Bouquet M; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Wilson ES; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Hyslop K; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Palmieri C; School of Veterinary Science, Faculty of Science, University of Queensland, Gatton, QLD, Australia., White N; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Queensland, Australia., Sato K; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Farah SM; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Gandini L; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Liu K; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Fior G; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Heinsar S; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.; Department of Intensive Care, North Estonia Medical Centre, Tallinn, Estonia.; Intensive Care Unit, St. Andrew's War Memorial Hospital, Brisbane, QLD, Australia., Ijuin S; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Kyun Ro S; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Abbate G; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Ainola C; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Sato N; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Lundon B; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Portatadino S; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Rachakonda RH; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia., Schneider B; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia., Harley A; Children's Intensive Care Research Program, Child Health Research Centre, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; Queensland Paediatric Sepsis Program, Children's Health and Youth Network, Children's Health Queensland, Brisbane, Queensland, Australia.; Critical Care Nursing Management Team, Queensland Children's Hospital, Brisbane, QLD, Australia.; School of Nursing, Midwifery and Social Work, University of Queensland, Brisbane, QLD, Australia., See Hoe LE; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia., Schembri MA; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia., Li Bassi G; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia.; Intensive Care Unit, St. Andrew's War Memorial Hospital, Brisbane, QLD, Australia., Fraser JF; Critical Care Research Group, The Prince Charles Hospital, 627 Rode Road, Level 3 Clinical Sciences Building, Chermside, Brisbane, QLD, 4032, Australia. j.fraser@uq.edu.au.; Institute for Molecular Bioscience (IMB), The University of Queensland, Brisbane, QLD, Australia. j.fraser@uq.edu.au.; Intensive Care Unit, St. Andrew's War Memorial Hospital, Brisbane, QLD, Australia. j.fraser@uq.edu.au.
Jazyk: angličtina
Zdroj: Intensive care medicine experimental [Intensive Care Med Exp] 2024 Oct 28; Vol. 12 (1), pp. 94. Date of Electronic Publication: 2024 Oct 28.
DOI: 10.1186/s40635-024-00684-x
Abstrakt: Background: Escherichia coli is the most common cause of human bloodstream infections and bacterial sepsis/septic shock. However, translation of preclinical septic shock resuscitative therapies remains limited mainly due to low-fidelity of available models in mimicking clinical illness. To overcome the translational barrier, we sought to replicate sepsis complexity by creating an acutely critically-ill preclinical bacterial septic shock model undergoing active 48-h intensive care management.
Aim: To develop a clinically relevant large-animal (ovine) live-bacterial infusion model for septic shock.
Methods: Septic shock was induced by intravenous infusion of the live antibiotic resistant extra-intestinal pathogenic E. coli sequence type 131 strain EC958 in eight anesthetised and mechanically ventilated sheep. A bacterial dose range of 2 × 10 5 -2 × 10 9  cfu/mL was used for the dose optimisation phase (n = 4) and upon dose confirmation the model was developed (n = 5). Post-shock the animals underwent an early-vasopressor and volume-restriction resuscitation strategy with active haemodynamic management and monitoring over 48 h. Serial blood samples were collected for testing of pro-inflammatory (IL-6, IL-8, VEGFA) and anti-inflammatory (IL-10) cytokines and hyaluronan assay to assess endothelial integrity. Tissue samples were collected for histopathology and transmission electron microscopy.
Results: The 2 × 10 7  cfu/mL bacterial dose led to a reproducible distributive shock within a pre-determined 12-h period. Five sheep were used to demonstrate consistency of the model. Bacterial infusion led to development of septic shock in all animals. The baseline mean arterial blood pressure reduced from a median of 91 mmHg (71, 102) to 50 mmHg (48, 57) (p = 0.004) and lactate levels increased from a median of 0.5 mM (0.3, 0.8) to 2.1 mM (2.0, 2.3) (p = 0.02) post-shock. The baseline median hyaluronan levels increased significantly from 25 ng/mL (18, 86) to 168 ng/mL (86, 569), p = 0.05 but not the median vasopressor dependency index which increased within 1 h of resuscitation from zero to 0.39 mmHg -1 (0.06, 5.13), p = 0.065, and. Over the 48 h, there was a significant decrease in the systemic vascular resistance index (F = 7.46, p = 0.01) and increase in the pro-inflammatory cytokines [IL-6 (F = 8.90, p = 0.02), IL-8 (F = 5.28, p = 0.03), and VEGFA (F = 6.47, p = 0.02)].
Conclusions: This critically ill large-animal model was consistent in reproducing septic shock and will be applied in investigating advanced resuscitation and therapeutic interventions.
(© 2024. The Author(s).)
Databáze: MEDLINE
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