Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients.
Aged
Animals
Apelin
/ genetics
Case-Control Studies
Catecholamines
/ metabolism
Enzymes
/ metabolism
Feces
Female
Follow-Up Studies
Hemodynamics
Humans
Male
Middle Aged
Pancreatic Elastase
/ genetics
Peritonitis
/ complications
Prognosis
Prospective Studies
Proteolysis
Sheep
Shock, Septic
/ etiology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
23 11 2021
23 11 2021
Historique:
received:
30
03
2021
accepted:
09
11
2021
entrez:
24
11
2021
pubmed:
25
11
2021
medline:
1
2
2022
Statut:
epublish
Résumé
Sepsis is a prevalent life-threatening condition related to a systemic infection, and with unresolved issues including refractory septic shock and organ failures. Endogenously released catecholamines are often inefficient to maintain blood pressure, and low reactivity to exogenous catecholamines with risk of sympathetic overstimulation is well documented in septic shock. In this context, apelinergics are efficient and safe inotrope and vasoregulator in rodents. However, their utility in a larger animal model as well as the limitations with regards to the enzymatic breakdown during sepsis, need to be investigated. The therapeutic potential and degradation of apelinergics in sepsis were tested experimentally and in a cohort of patients. (1) 36 sheep with or without fecal peritonitis-induced septic shock (a large animal experimental design aimed to mimic the human septic shock paradigm) were evaluated for hemodynamic and renal responsiveness to incremental doses of two dominant apelinergics: apelin-13 (APLN-13) or Elabela (ELA), and (2) 52 subjects (33 patients with sepsis/septic shock and 19 healthy volunteers) were investigated for early levels of endogenous apelinergics in the blood, the related enzymatic degradation profile, and data regarding sepsis outcome. APLN-13 was the only one apelinergic which efficiently improved hemodynamics in both healthy and septic sheep. Endogenous apelinergic levels early rose, and specific enzymatic breakdown activities potentially threatened endogenous apelin system reactivity and negatively impacted the outcome in human sepsis. Short-term exogenous APLN-13 infusion is helpful in stabilizing cardiorenal functions in ovine septic shock; however, this ability might be impaired by specific enzymatic systems triggered during the early time course of human sepsis. Strategies to improve resistance of APLN-13 to degradation and/or to overcome sepsis-induced enzymatic breakdown environment should guide future works.
Identifiants
pubmed: 34815457
doi: 10.1038/s41598-021-02087-4
pii: 10.1038/s41598-021-02087-4
pmc: PMC8611018
doi:
Substances chimiques
APLN protein, human
0
Apelin
0
Catecholamines
0
Enzymes
0
CELA1 protein, human
EC 3.4.21.36
Pancreatic Elastase
EC 3.4.21.36
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22770Subventions
Organisme : the Canadian Institutes of Health Research (CIHR)
ID : Project grants #376770
Organisme : the Canadian Institutes of Health Research (CIHR)
ID : Project grants #376770
Organisme : the Canadian Institutes of Health Research (CIHR)
ID : Project grants #376770
Organisme : the Canadian Institutes of Health Research (CIHR)
ID : Project grants #376770
Informations de copyright
© 2021. The Author(s).
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