Asphyxia-Induced Bacterial Translocation in an Animal Experimental Model in Neonatal Piglets

Background: The term “bacterial translocation” (BT) refers to the migration of bacteria or their products from the gastrointestinal tract to tissues located outside it, and may occur after intestinal ischemia-reperfusion injury. The term “endotoxin” is synonymous, and is used interchangeably with the term lipopolysaccharide (LPS). LPS, a component of Gram-negative gut bacteria, is a potent microbial virulence factor, that can trigger production of pro-inflammatory mediators, causing localized and systemic inflammation. The aim of this study is to investigate if neonatal asphyxia provokes BT and an increased concentration of LPS in an animal model of asphyxia in piglets. Methods: Twenty-one (21) newborn male Landrace/Large White piglets, 1–4 days old, were randomly allocated into three groups, Control (A), Asphyxia (B) and Asphyxia-Cardiopulmonary Resuscitation (CPR) (C). All animals were instrumented, anesthetized and underwent hemodynamic monitoring. In Group A, the animals were euthanized. In Group B, the endotracheal tube was occluded to cause asphyxia leading to cardiopulmonary arrest. In Group C, the animals were resuscitated after asphyxia and further monitored for 30′. Bacterial translocation was assessed by the measurement of endotoxin in blood from the portal vein and the aorta, and also by the measurement of endotoxin in mesenteric lymph nodes (MLNs) at euthanasia. The results are given as median (IQR) with LPS concentration in EU/mL. Results: BT was observed in all groups with minimum LPS concentration in the MLN and maximum concentration in the portal vein. LPS levels in the MLNs were higher in the Group B: 6.38 EU/mL (2.69–9.34) compared to the other groups (Group A: 2.1 EU/mL (1.08–2.52), Group C: 1.66 EU/mL (1.51–2.48), p = 0.012). The aorta to MLNs LPS difference (%) was lower in Group B: 0.13% (0.04–1.17), compared to Group A: 5.08% (2.2–10.7), and Group C: 3.42% (1.5–5.1)) (p = 0.042). The same was detected for portal to MLNs LPS difference (%) which was lower in Group B: 0.94% (0.5–3) compared to Group A: 4.9% (4–15), and Group C: 3.85% (1.5–5.1)) (p = 0.044). Conclusions: Neonatal asphyxia can provoke ΒΤ and increased LPS concentration in blood and tissue located outside the gastrointestinal system.

[1]  N. Iacovidou,et al.  Microbial Translocation and Perinatal Asphyxia/Hypoxia: A Systematic Review , 2022, Diagnostics.

[2]  C. Morley,et al.  European Resuscitation Council Guidelines 2021: Newborn resuscitation and support of transition of infants at birth. , 2021, Resuscitation.

[3]  M. Gazouli,et al.  Assessment of Post-Resuscitation Intestinal Injury and Timing of Bacterial Translocation in Swine Anaesthetized With Propofol-Based Total Intravenous Anaesthesia , 2020, Cureus.

[4]  G. Dukic,et al.  European , 2020, Definitions.

[5]  Adrian J. Smith,et al.  The Role of the Three Rs in Improving the Planning and Reproducibility of Animal Experiments , 2019, Animals : an open access journal from MDPI.

[6]  D. Lewis Animal experimentation: implementation and application of the 3Rs. , 2019, Emerging topics in life sciences.

[7]  A. Chalkias,et al.  Intraoperative initiation of a modified ARDSNet protocol increases survival of septic patients with severe acute respiratory distress syndrome. , 2018, Heart & lung : the journal of critical care.

[8]  N. Iacovidou,et al.  Resuscitation with centhaquin and 6% hydroxyethyl starch 130/0.4 improves survival in a swine model of hemorrhagic shock: a randomized experimental study , 2018, European Journal of Trauma and Emergency Surgery.

[9]  A. Chalkias,et al.  Microcirculation-mediated preconditioning and intracellular hypothermia. , 2018, Medical hypotheses.

[10]  C. Hunter,et al.  The science and necessity of using animal models in the study of necrotizing enterocolitis. , 2018, Seminars in pediatric surgery.

[11]  G. Finco,et al.  Metabolomics profiling reveals different patterns in an animal model of asphyxial and dysrhythmic cardiac arrest , 2017, Scientific Reports.

[12]  A. Chalkias,et al.  Centhaquin Effects in a Swine Model of Ventricular Fibrillation: Centhaquin and Cardiac Arrest. , 2017, Heart, lung & circulation.

[13]  Z. Molnár,et al.  Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges , 2017, Front. Cell. Neurosci..

[14]  R. Munford Endotoxemia—menace, marker, or mistake? , 2016, Journal of leukocyte biology.

[15]  J. Perlman,et al.  Pathophysiology of Birth Asphyxia. , 2016, Clinics in perinatology.

[16]  J. Mira,et al.  High Level of Endotoxemia Following Out-of-Hospital Cardiac Arrest Is Associated With Severity and Duration of Postcardiac Arrest Shock* , 2015, Critical care medicine.

[17]  Daniele Trevisanuto,et al.  European Resuscitation Council Guidelines for Resuscitation 2015: Section 7. Resuscitation and support of transition of babies at birth. , 2015, Resuscitation.

[18]  X. Montagutelli,et al.  Animal models are essential to biological research: issues and perspectives , 2015, Future science OA.

[19]  P. Denning,et al.  Intestinal microbiota and its relationship with necrotizing enterocolitis , 2015, Pediatric Research.

[20]  A. Chalkias,et al.  Cardiopulmonary Arrest and Resuscitation in Severe Sepsis and Septic Shock: A Research Model , 2015, Shock.

[21]  R. Antonucci,et al.  Perinatal asphyxia in the term newborn , 2014 .

[22]  H. Ford,et al.  Late onset of necrotizing enterocolitis in the full-term infant is associated with increased mortality: results from a two-center analysis. , 2014, Journal of pediatric surgery.

[23]  A. Chalkias,et al.  Addition of glucagon to adrenaline improves hemodynamics in a porcine model of prolonged ventricular fibrillation. , 2014, The American journal of emergency medicine.

[24]  A. Pease,et al.  Acute necrotizing enterocolitis of preterm piglets is characterized by dysbiosis of ileal mucosa-associated bacteria , 2011, Gut microbes.

[25]  Jeffrey S Upperman,et al.  Disordered enterocyte signaling and intestinal barrier dysfunction in the pathogenesis of necrotizing enterocolitis. , 2005, Seminars in pediatric surgery.

[26]  B. Beutler,et al.  Innate immune sensing and its roots: the story of endotoxin , 2003, Nature Reviews Immunology.

[27]  D. Waxman,et al.  Evaluation of the newborn's blood gas status. National Academy of Clinical Biochemistry. , 1997, Clinical chemistry.

[28]  H. Redl,et al.  Kinetics of Endotoxin and Tumor Necrosis Factor Appearance in Portal and Systemic Circulation After Hemorrhagic Shock in Rats , 1995, Annals of surgery.

[29]  S. Deventer,et al.  Intestinal endotoxemia: Clinical significance , 1988 .

[30]  J. T. ten Cate,et al.  Intestinal endotoxemia. Clinical significance. , 1988, Gastroenterology.

[31]  S. Gennaro Neonatal necrotizing enterocolitis. , 1981, Critical care update.