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Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial

INTRODUCTION: Sepsis impairs gastrointestinal microcirculation and it is hypothesized that this might increase patient’s mortality. Sub-therapeutic vasopressin improves gastric microcirculation under physiologic conditions whereas a therapeutic dosing regimen seems to be rather detrimental. However,...

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Autores principales: Schulz, Jan, Bauer, Inge, Herminghaus, Anna, Picker, Olaf, Truse, Richard, Vollmer, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460032/
https://www.ncbi.nlm.nih.gov/pubmed/34555053
http://dx.doi.org/10.1371/journal.pone.0257034
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author Schulz, Jan
Bauer, Inge
Herminghaus, Anna
Picker, Olaf
Truse, Richard
Vollmer, Christian
author_facet Schulz, Jan
Bauer, Inge
Herminghaus, Anna
Picker, Olaf
Truse, Richard
Vollmer, Christian
author_sort Schulz, Jan
collection PubMed
description INTRODUCTION: Sepsis impairs gastrointestinal microcirculation and it is hypothesized that this might increase patient’s mortality. Sub-therapeutic vasopressin improves gastric microcirculation under physiologic conditions whereas a therapeutic dosing regimen seems to be rather detrimental. However, the effects of sub-therapeutic vasopressin on gastrointestinal microcirculation in sepsis are largely unknown. Therefore, we conducted this trial to investigate the effect of sub-therapeutic as well as therapeutic vasopressin on gastrointestinal microcirculation in sepsis. METHODS: 40 male Wistar rats were randomized into 4 groups. Colon ascendens stent peritonitis (CASP)-surgery was performed to establish mild or moderate sepsis. 24 hours after surgery, animals received either vasopressin with increasing dosages every 30 min (6.75, 13.5 (sub-therapeutic), 27 mU · kg(-1) · h(-1) (therapeutic)) or vehicle. Microcirculatory oxygenation (μHBO(2)) of the colon was recorded for 90 min using tissue reflectance spectrophotometry. Intestinal microcirculatory perfusion (total vessel density (TVD; mm/mm(2)) and perfused vessel density (PVD; mm/mm(2))) were measured using incident dark field-Imaging at baseline and after 60 min. RESULTS: In mild as well as in moderate septic animals with vehicle-infusion intestinal μHbO(2), TVD and PVD remained constant. In contrast, in moderate sepsis, sub-therapeutic vasopressin with 13.5 mU · kg(-1) · h(-1) elevated intestinal μHBO(2) (+ 6.1 ± 5.3%; p < 0.05 vs. baseline) and TVD (+ 5.2 ± 3.0 mm/mm(2); p < 0.05 vs. baseline). μHBO(2), TVD and PVD were significantly increased compared to moderate sepsis alone. However, therapeutic vasopressin did not change intestinal microcirculation. In mild septic animals sub-therapeutic as well as therapeutic vasopressin had no relevant effect on gastrointestinal microcirculation. Systemic blood pressure remained constant in all groups. CONCLUSION: Sub-therapeutic vasopressin improves gastrointestinal microcirculatory oxygenation in moderate sepsis without altering systemic blood pressure. This protective effect seems to be mediated by an enhanced microcirculatory perfusion and thereby increased oxygen supply. In contrast, therapeutic vasopressin did not show this beneficial effect.
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spelling pubmed-84600322021-09-24 Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial Schulz, Jan Bauer, Inge Herminghaus, Anna Picker, Olaf Truse, Richard Vollmer, Christian PLoS One Research Article INTRODUCTION: Sepsis impairs gastrointestinal microcirculation and it is hypothesized that this might increase patient’s mortality. Sub-therapeutic vasopressin improves gastric microcirculation under physiologic conditions whereas a therapeutic dosing regimen seems to be rather detrimental. However, the effects of sub-therapeutic vasopressin on gastrointestinal microcirculation in sepsis are largely unknown. Therefore, we conducted this trial to investigate the effect of sub-therapeutic as well as therapeutic vasopressin on gastrointestinal microcirculation in sepsis. METHODS: 40 male Wistar rats were randomized into 4 groups. Colon ascendens stent peritonitis (CASP)-surgery was performed to establish mild or moderate sepsis. 24 hours after surgery, animals received either vasopressin with increasing dosages every 30 min (6.75, 13.5 (sub-therapeutic), 27 mU · kg(-1) · h(-1) (therapeutic)) or vehicle. Microcirculatory oxygenation (μHBO(2)) of the colon was recorded for 90 min using tissue reflectance spectrophotometry. Intestinal microcirculatory perfusion (total vessel density (TVD; mm/mm(2)) and perfused vessel density (PVD; mm/mm(2))) were measured using incident dark field-Imaging at baseline and after 60 min. RESULTS: In mild as well as in moderate septic animals with vehicle-infusion intestinal μHbO(2), TVD and PVD remained constant. In contrast, in moderate sepsis, sub-therapeutic vasopressin with 13.5 mU · kg(-1) · h(-1) elevated intestinal μHBO(2) (+ 6.1 ± 5.3%; p < 0.05 vs. baseline) and TVD (+ 5.2 ± 3.0 mm/mm(2); p < 0.05 vs. baseline). μHBO(2), TVD and PVD were significantly increased compared to moderate sepsis alone. However, therapeutic vasopressin did not change intestinal microcirculation. In mild septic animals sub-therapeutic as well as therapeutic vasopressin had no relevant effect on gastrointestinal microcirculation. Systemic blood pressure remained constant in all groups. CONCLUSION: Sub-therapeutic vasopressin improves gastrointestinal microcirculatory oxygenation in moderate sepsis without altering systemic blood pressure. This protective effect seems to be mediated by an enhanced microcirculatory perfusion and thereby increased oxygen supply. In contrast, therapeutic vasopressin did not show this beneficial effect. Public Library of Science 2021-09-23 /pmc/articles/PMC8460032/ /pubmed/34555053 http://dx.doi.org/10.1371/journal.pone.0257034 Text en © 2021 Schulz et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Schulz, Jan
Bauer, Inge
Herminghaus, Anna
Picker, Olaf
Truse, Richard
Vollmer, Christian
Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial
title Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial
title_full Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial
title_fullStr Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial
title_full_unstemmed Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial
title_short Sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: A randomized, placebo-controlled, blinded trial
title_sort sub-therapeutic vasopressin but not therapeutic vasopressin improves gastrointestinal microcirculation in septic rats: a randomized, placebo-controlled, blinded trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460032/
https://www.ncbi.nlm.nih.gov/pubmed/34555053
http://dx.doi.org/10.1371/journal.pone.0257034
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