Inhibition of circulating dipeptidyl-peptidase 3 by procizumab in experimental septic shock reduces catecholamine exposure and myocardial injury.
Angiotensin II
Dipeptidyl peptidase 3
Renin–angiotensin system
Sepsis
Shock
Vasopressors
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:
07 Jun 2024
07 Jun 2024
Historique:
received:
22
04
2024
accepted:
29
05
2024
medline:
8
6
2024
pubmed:
8
6
2024
entrez:
7
6
2024
Statut:
epublish
Résumé
Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock. In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65-75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment ( PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling.
Sections du résumé
BACKGROUND
BACKGROUND
Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock.
METHODS
METHODS
In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65-75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (
RESULTS
RESULTS
PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO
CONCLUSIONS
CONCLUSIONS
In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling.
Identifiants
pubmed: 38849640
doi: 10.1186/s40635-024-00638-3
pii: 10.1186/s40635-024-00638-3
doi:
Types de publication
Journal Article
Langues
eng
Pagination
53Informations de copyright
© 2024. The Author(s).
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