Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients
Abstract 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 catechola...
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Nature Portfolio
2021
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oai:doaj.org-article:01d655baf6da4408a83a36f90f682b232021-11-28T12:17:47ZApelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients10.1038/s41598-021-02087-42045-2322https://doaj.org/article/01d655baf6da4408a83a36f90f682b232021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02087-4https://doaj.org/toc/2045-2322Abstract 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.David CoquerelJulie LamoureuxFrédéric ChagnonKien TrânMichael SageEtienne Fortin-PellerinEugénie DelileXavier SainsilyJustin FournierAudrey-Ann DumontMannix Auger-MessierPhilippe SarretEric MarsaultJean-Paul PraudTamàs FülöpOlivier LesurNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) |
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Medicine R Science Q David Coquerel Julie Lamoureux Frédéric Chagnon Kien Trân Michael Sage Etienne Fortin-Pellerin Eugénie Delile Xavier Sainsily Justin Fournier Audrey-Ann Dumont Mannix Auger-Messier Philippe Sarret Eric Marsault Jean-Paul Praud Tamàs Fülöp Olivier Lesur Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients |
| description |
Abstract 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. |
| format |
article |
| author |
David Coquerel Julie Lamoureux Frédéric Chagnon Kien Trân Michael Sage Etienne Fortin-Pellerin Eugénie Delile Xavier Sainsily Justin Fournier Audrey-Ann Dumont Mannix Auger-Messier Philippe Sarret Eric Marsault Jean-Paul Praud Tamàs Fülöp Olivier Lesur |
| author_facet |
David Coquerel Julie Lamoureux Frédéric Chagnon Kien Trân Michael Sage Etienne Fortin-Pellerin Eugénie Delile Xavier Sainsily Justin Fournier Audrey-Ann Dumont Mannix Auger-Messier Philippe Sarret Eric Marsault Jean-Paul Praud Tamàs Fülöp Olivier Lesur |
| author_sort |
David Coquerel |
| title |
Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients |
| title_short |
Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients |
| title_full |
Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients |
| title_fullStr |
Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients |
| title_full_unstemmed |
Apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients |
| title_sort |
apelin-13 in septic shock: effective in supporting hemodynamics in sheep but compromised by enzymatic breakdown in patients |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/01d655baf6da4408a83a36f90f682b23 |
| work_keys_str_mv |
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