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The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice

BACKGROUND: While most studies focus on cardiovascular morbidity following anesthesia and surgery in excessive obesity, it is unknown whether these intraoperative cardiovascular alterations also occur in milder forms of adiposity without type 2 diabetes and if insulin is a possible treatment to impr...

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Autores principales: Boly, Chantal A., Eringa, Etto C., Bouwman, R. Arthur, van den Akker, Rob F. P., de Man, Frances S., Schalij, Ingrid, Loer, Stephan A., Boer, Christa, van den Brom, Charissa E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029087/
https://www.ncbi.nlm.nih.gov/pubmed/27651131
http://dx.doi.org/10.1186/s12933-016-0453-y
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author Boly, Chantal A.
Eringa, Etto C.
Bouwman, R. Arthur
van den Akker, Rob F. P.
de Man, Frances S.
Schalij, Ingrid
Loer, Stephan A.
Boer, Christa
van den Brom, Charissa E.
author_facet Boly, Chantal A.
Eringa, Etto C.
Bouwman, R. Arthur
van den Akker, Rob F. P.
de Man, Frances S.
Schalij, Ingrid
Loer, Stephan A.
Boer, Christa
van den Brom, Charissa E.
author_sort Boly, Chantal A.
collection PubMed
description BACKGROUND: While most studies focus on cardiovascular morbidity following anesthesia and surgery in excessive obesity, it is unknown whether these intraoperative cardiovascular alterations also occur in milder forms of adiposity without type 2 diabetes and if insulin is a possible treatment to improve intraoperative myocardial performance. In this experimental study we investigated whether mild adiposity without metabolic alterations is already associated with cardiometabolic dysfunction during anesthesia, mechanical ventilation and surgery and whether these myocardial alterations can be neutralized by intraoperative insulin treatment. METHODS: Mice were fed a western (WD) or control diet (CD) for 4 weeks. After metabolic profiling, mice underwent general anesthesia, mechanical ventilation and surgery. Cardiac function was determined with echocardiography and left-ventricular pressure–volume analysis. Myocardial perfusion was determined with contrast-enhanced echocardiography. WD-fed mice were subsequently treated with insulin by hyperinsulinemic euglycemic clamping followed by the same measurements of cardiac function and perfusion. RESULTS: Western-type diet feeding led to a 13 % increase in bodyweight, (p < 0.0001) and increased adipose tissue mass, without metabolic alterations. Despite this mild phenotype, WD-fed mice had decreased systolic and diastolic function (end-systolic elastance was 2.0 ± 0.5 versus 4.1 ± 2.4 mmHg/μL, p = 0.01 and diastolic beta was 0.07 ± 0.03 versus 0.04 ± 0.01 mmHg/μL, p = 0.02) compared to CD-fed mice. Ventriculo-arterial coupling and myocardial perfusion were decreased by 48 % (p = 0.003) and 43 % (p = 0.03) respectively. Insulin treatment in WD-fed mice improved echo-derived systolic function (fractional shortening 42 ± 5 % to 46 ± 3, p = 0.05), likely due to decreased afterload, but there was no effect on load-independent measures of systolic function or myocardial perfusion. However, there was a trend towards improved diastolic function after insulin treatment (43 % improvement, p = 0.05) in WD-fed mice. CONCLUSIONS: Mild adiposity without metabolic alterations already affected cardiac function and perfusion during anesthesia, mechanical ventilation and surgery in mice. Intraoperative insulin may be beneficial to reduce afterload and enhance intraoperative ventricular relaxation, but not to improve ventricular contractility or myocardial perfusion.
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spelling pubmed-50290872016-09-27 The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice Boly, Chantal A. Eringa, Etto C. Bouwman, R. Arthur van den Akker, Rob F. P. de Man, Frances S. Schalij, Ingrid Loer, Stephan A. Boer, Christa van den Brom, Charissa E. Cardiovasc Diabetol Original Investigation BACKGROUND: While most studies focus on cardiovascular morbidity following anesthesia and surgery in excessive obesity, it is unknown whether these intraoperative cardiovascular alterations also occur in milder forms of adiposity without type 2 diabetes and if insulin is a possible treatment to improve intraoperative myocardial performance. In this experimental study we investigated whether mild adiposity without metabolic alterations is already associated with cardiometabolic dysfunction during anesthesia, mechanical ventilation and surgery and whether these myocardial alterations can be neutralized by intraoperative insulin treatment. METHODS: Mice were fed a western (WD) or control diet (CD) for 4 weeks. After metabolic profiling, mice underwent general anesthesia, mechanical ventilation and surgery. Cardiac function was determined with echocardiography and left-ventricular pressure–volume analysis. Myocardial perfusion was determined with contrast-enhanced echocardiography. WD-fed mice were subsequently treated with insulin by hyperinsulinemic euglycemic clamping followed by the same measurements of cardiac function and perfusion. RESULTS: Western-type diet feeding led to a 13 % increase in bodyweight, (p < 0.0001) and increased adipose tissue mass, without metabolic alterations. Despite this mild phenotype, WD-fed mice had decreased systolic and diastolic function (end-systolic elastance was 2.0 ± 0.5 versus 4.1 ± 2.4 mmHg/μL, p = 0.01 and diastolic beta was 0.07 ± 0.03 versus 0.04 ± 0.01 mmHg/μL, p = 0.02) compared to CD-fed mice. Ventriculo-arterial coupling and myocardial perfusion were decreased by 48 % (p = 0.003) and 43 % (p = 0.03) respectively. Insulin treatment in WD-fed mice improved echo-derived systolic function (fractional shortening 42 ± 5 % to 46 ± 3, p = 0.05), likely due to decreased afterload, but there was no effect on load-independent measures of systolic function or myocardial perfusion. However, there was a trend towards improved diastolic function after insulin treatment (43 % improvement, p = 0.05) in WD-fed mice. CONCLUSIONS: Mild adiposity without metabolic alterations already affected cardiac function and perfusion during anesthesia, mechanical ventilation and surgery in mice. Intraoperative insulin may be beneficial to reduce afterload and enhance intraoperative ventricular relaxation, but not to improve ventricular contractility or myocardial perfusion. BioMed Central 2016-09-20 /pmc/articles/PMC5029087/ /pubmed/27651131 http://dx.doi.org/10.1186/s12933-016-0453-y Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Original Investigation
Boly, Chantal A.
Eringa, Etto C.
Bouwman, R. Arthur
van den Akker, Rob F. P.
de Man, Frances S.
Schalij, Ingrid
Loer, Stephan A.
Boer, Christa
van den Brom, Charissa E.
The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice
title The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice
title_full The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice
title_fullStr The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice
title_full_unstemmed The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice
title_short The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice
title_sort effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029087/
https://www.ncbi.nlm.nih.gov/pubmed/27651131
http://dx.doi.org/10.1186/s12933-016-0453-y
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