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Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment

Autonomic and vascular failures are common phenotypes of sepsis, typically characterized by tachycardia despite corrected hypotension/hypovolemia, vasopressor resistance, increased arterial stiffness and decreased peripheral vascular resistance. In a 5-day swine experiment of polymicrobial sepsis we...

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Autores principales: Carrara, Marta, Antenucci, Pietro, Liu, Shengchen, Kohler, Andreas, Langer, Rupert, Jakob, Stephan M., Ferrario, Manuela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9652343/
https://www.ncbi.nlm.nih.gov/pubmed/36369521
http://dx.doi.org/10.1038/s41598-022-23516-y
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author Carrara, Marta
Antenucci, Pietro
Liu, Shengchen
Kohler, Andreas
Langer, Rupert
Jakob, Stephan M.
Ferrario, Manuela
author_facet Carrara, Marta
Antenucci, Pietro
Liu, Shengchen
Kohler, Andreas
Langer, Rupert
Jakob, Stephan M.
Ferrario, Manuela
author_sort Carrara, Marta
collection PubMed
description Autonomic and vascular failures are common phenotypes of sepsis, typically characterized by tachycardia despite corrected hypotension/hypovolemia, vasopressor resistance, increased arterial stiffness and decreased peripheral vascular resistance. In a 5-day swine experiment of polymicrobial sepsis we aimed at characterizing arterial properties and autonomic mechanisms responsible for cardiovascular homeostasis regulation, with the final goal to verify whether the resuscitation therapy in agreement with standard guidelines was successful in restoring a physiological condition of hemodynamic profile, cardiovascular interactions and autonomic control. Twenty pigs were randomized to polymicrobial sepsis and protocol-based resuscitation or to prolonged mechanical ventilation and sedation without sepsis. The animals were studied at baseline, after sepsis development, and every 24 h during the 3-days resuscitation period. Beat-to-beat carotid blood pressure (BP), carotid blood flow, and central venous pressure were continuously recorded. The two-element Windkessel model was adopted to study carotid arterial compliance, systemic vascular resistance and characteristic time constant τ. Effective arterial elastance was calculated as a simple estimate of total arterial load. Cardiac baroreflex sensitivity (BRS) and low frequency (LF) spectral power of diastolic BP were computed to assess autonomic activity. Sepsis induced significant vascular and autonomic alterations, manifested as increased arterial stiffness, decreased vascular resistance and τ constant, reduced BRS and LF power, higher arterial afterload and elevated heart rate in septic pigs compared to sham animals. This compromised condition was persistent until the end of the experiment, despite achievement of recommended resuscitation goals by administered vasopressors and fluids. Vascular and autonomic alterations persist 3 days after goal-directed resuscitation in a clinically relevant sepsis model. We hypothesize that the addition of these variables to standard clinical markers may better profile patients’ response to treatment and this could drive a more tailored therapy which could have a potential impact on long-term outcomes.
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spelling pubmed-96523432022-11-15 Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment Carrara, Marta Antenucci, Pietro Liu, Shengchen Kohler, Andreas Langer, Rupert Jakob, Stephan M. Ferrario, Manuela Sci Rep Article Autonomic and vascular failures are common phenotypes of sepsis, typically characterized by tachycardia despite corrected hypotension/hypovolemia, vasopressor resistance, increased arterial stiffness and decreased peripheral vascular resistance. In a 5-day swine experiment of polymicrobial sepsis we aimed at characterizing arterial properties and autonomic mechanisms responsible for cardiovascular homeostasis regulation, with the final goal to verify whether the resuscitation therapy in agreement with standard guidelines was successful in restoring a physiological condition of hemodynamic profile, cardiovascular interactions and autonomic control. Twenty pigs were randomized to polymicrobial sepsis and protocol-based resuscitation or to prolonged mechanical ventilation and sedation without sepsis. The animals were studied at baseline, after sepsis development, and every 24 h during the 3-days resuscitation period. Beat-to-beat carotid blood pressure (BP), carotid blood flow, and central venous pressure were continuously recorded. The two-element Windkessel model was adopted to study carotid arterial compliance, systemic vascular resistance and characteristic time constant τ. Effective arterial elastance was calculated as a simple estimate of total arterial load. Cardiac baroreflex sensitivity (BRS) and low frequency (LF) spectral power of diastolic BP were computed to assess autonomic activity. Sepsis induced significant vascular and autonomic alterations, manifested as increased arterial stiffness, decreased vascular resistance and τ constant, reduced BRS and LF power, higher arterial afterload and elevated heart rate in septic pigs compared to sham animals. This compromised condition was persistent until the end of the experiment, despite achievement of recommended resuscitation goals by administered vasopressors and fluids. Vascular and autonomic alterations persist 3 days after goal-directed resuscitation in a clinically relevant sepsis model. We hypothesize that the addition of these variables to standard clinical markers may better profile patients’ response to treatment and this could drive a more tailored therapy which could have a potential impact on long-term outcomes. Nature Publishing Group UK 2022-11-11 /pmc/articles/PMC9652343/ /pubmed/36369521 http://dx.doi.org/10.1038/s41598-022-23516-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Carrara, Marta
Antenucci, Pietro
Liu, Shengchen
Kohler, Andreas
Langer, Rupert
Jakob, Stephan M.
Ferrario, Manuela
Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment
title Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment
title_full Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment
title_fullStr Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment
title_full_unstemmed Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment
title_short Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment
title_sort autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9652343/
https://www.ncbi.nlm.nih.gov/pubmed/36369521
http://dx.doi.org/10.1038/s41598-022-23516-y
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