A model of porcine polymicrobial septic shock.
Animal model
Faecal peritonitis
Pig
Sepsis
Septic shock
Journal
Intensive care medicine experimental
ISSN: 2197-425X
Titre abrégé: Intensive Care Med Exp
Pays: Germany
ID NLM: 101645149
Informations de publication
Date de publication:
02 Jun 2023
02 Jun 2023
Historique:
received:
14
12
2022
accepted:
21
04
2023
medline:
2
6
2023
pubmed:
2
6
2023
entrez:
1
6
2023
Statut:
epublish
Résumé
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs. The literature search was performed using the keywords "pig", "sepsis" and "septic shock". For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA. Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred. We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.
Sections du résumé
BACKGROUND
BACKGROUND
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs.
MATERIALS AND METHODS
METHODS
The literature search was performed using the keywords "pig", "sepsis" and "septic shock". For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA.
RESULTS
RESULTS
Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred.
CONCLUSIONS
CONCLUSIONS
We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.
Identifiants
pubmed: 37264259
doi: 10.1186/s40635-023-00513-7
pii: 10.1186/s40635-023-00513-7
pmc: PMC10235002
doi:
Types de publication
Journal Article
Langues
eng
Pagination
31Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : WA3786/3-1
Informations de copyright
© 2023. The Author(s).
Références
J Clin Monit Comput. 2007 Aug;21(4):237-42
pubmed: 17541714
J Pers Med. 2021 Feb 28;11(3):
pubmed: 33670874
JAMA. 2016 Feb 23;315(8):801-10
pubmed: 26903338
Intensive Care Med Exp. 2018 Aug 14;6(1):26
pubmed: 30112605
Intensive Care Med. 2018 Jun;44(6):925-928
pubmed: 29675566
Acta Anaesthesiol Scand. 2006 Apr;50(4):407-13
pubmed: 16548852
J Immunol. 2013 Jul 15;191(2):819-27
pubmed: 23761634
Intensive Care Med. 2017 Mar;43(3):304-377
pubmed: 28101605
Biomed Res Int. 2015;2015:181845
pubmed: 26543849
Trends Microbiol. 2012 Jan;20(1):50-7
pubmed: 22153753
Sci Transl Med. 2021 Nov 24;13(621):eabd5758
pubmed: 34818055
Intensive Care Med Exp. 2019 Jul 25;7(Suppl 1):45
pubmed: 31346833
Shock. 2015 Mar;43(3):285-91
pubmed: 25394247
J Invest Surg. 2001 Jul-Aug;14(4):195-212
pubmed: 11680530
Crit Care Med. 2009 Jan;37(1 Suppl):S30-7
pubmed: 19104223
Clin Hemorheol Microcirc. 2021;78(3):325-338
pubmed: 33843666
Intensive Care Med Exp. 2016 Dec;4(1):14
pubmed: 27271248
Vet Microbiol. 2021 Feb;253:108958
pubmed: 33387911
Virulence. 2014 Jan 1;5(1):143-53
pubmed: 24022070
Intensive Care Med. 2018 Sep;44(9):1400-1426
pubmed: 29971592
Intensive Care Med Exp. 2018 Aug 8;6(1):24
pubmed: 30091119
Am J Respir Cell Mol Biol. 2021 Aug;65(2):167-175
pubmed: 33798037
J Surg Res. 2019 Dec;244:492-501
pubmed: 31330293
Exp Mol Med. 2021 Jul;53(7):1116-1123
pubmed: 34253862
Crit Care Med. 2021 Nov 1;49(11):e1063-e1143
pubmed: 34605781
Clin Kidney J. 2020 Oct 10;14(2):526-536
pubmed: 33623675
J Anim Sci. 1973 May;36(5):927-30
pubmed: 4703721
Br J Anaesth. 2022 May;128(5):864-873
pubmed: 35131096
Semin Immunopathol. 2017 Jul;39(5):517-528
pubmed: 28555385
Shock. 2005 Dec;24 Suppl 1:1-6
pubmed: 16374365
Crit Care. 2019 Jan 17;23(1):16
pubmed: 30654825
Curr Infect Dis Rep. 2016 Sep;18(9):26
pubmed: 27432263
Acta Anaesthesiol Scand. 2015 Mar;59(3):346-53
pubmed: 25557933
Trends Microbiol. 2011 Apr;19(4):198-208
pubmed: 21296575
Nat Protoc. 2009;4(1):31-6
pubmed: 19131954
J Am Soc Nephrol. 2011 Mar;22(3):484-95
pubmed: 21355054
Front Med (Lausanne). 2022 May 09;9:867796
pubmed: 35615093