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The antisecretory p...
The antisecretory peptide AF-16 may modulate tissue edema but not inflammation in experimental peritonitis induced sepsis
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- Barrueta Tenhunen, Annelie (författare)
- Uppsala universitet,Hedenstiernalaboratoriet,Anestesiologi och intensivvård
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- van der Heijden, Jaap (författare)
- Uppsala universitet,Anestesiologi och intensivvård
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- Blokhin, Ivan (författare)
- Uppsala universitet,Anestesiologi och intensivvård
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- Massaro, Fabrizia (författare)
- Uppsala universitet,Hedenstiernalaboratoriet,Cardiac Anesthesia and Intensive Care, Anthea Hospital, GVM Care & Research, Bari, Italy
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- Hansson, Hans-Arne, 1939 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine,Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden
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- Feinstein, R. (författare)
- Department of Pathology and Wildlife Diseases, National Veterinary Institute, Uppsala, Sweden
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- Larsson, Anders (författare)
- Uppsala universitet,Klinisk kemi,Hedenstiernalaboratoriet
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- Tenhunen, Jyrki (författare)
- Uppsala universitet,Anestesiologi och intensivvård
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(creator_code:org_t)
- 2020-08-21
- 2020
- Engelska.
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its' anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n = 8) or control (saline, n = 8) group. After the onset of hemodynamic instability (defined as mean arterial pressure < 60 mmHg maintained for > 5 minutes), intervention with AF-16 (20 mg/kg (50 mg/ml) in 0.9% saline) intravenously (only the vehicle in the control group) and a protocolized resuscitation was started. We recorded respiratory and hemodynamic parameters hourly for twenty hours or until the animal died and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, overall fluid balance, lung mechanics, gas exchange or histology. However, liver wet-to-dry ratio remained lower in AF-16 treated animals as compared to controls, 3.1 +/- 0.4, (2.7-3.5, 95% CI, n = 8) vs 4.0 +/- 0.6 (3.4-4.5, 95% CI, n = 8),p= 0.006, respectively. Bearing in mind the limited sample size, this experimental pilot study suggests that AF-16 may inhibit sepsis induced liver edema in peritonitis-sepsis.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Anestesi och intensivvård (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Anesthesiology and Intensive Care (hsv//eng)
Nyckelord
- international consensus definitions
- septic shock
- clinical-criteria
- critically-ill
- animal-models
- mortality
- overload
- increase
- outcomes
- Science & Technology - Other Topics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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