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Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest
INTRODUCTION: Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calciu...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056352/ https://www.ncbi.nlm.nih.gov/pubmed/24138817 http://dx.doi.org/10.1186/cc13071 |
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author | Rungatscher, Alessio Hallström, Seth Giacomazzi, Alice Linardi, Daniele Milani, Elisabetta Tessari, Maddalena Luciani, Giovanni Battista Scarabelli, Tiziano M Mazzucco, Alessandro Faggian, Giuseppe |
author_facet | Rungatscher, Alessio Hallström, Seth Giacomazzi, Alice Linardi, Daniele Milani, Elisabetta Tessari, Maddalena Luciani, Giovanni Battista Scarabelli, Tiziano M Mazzucco, Alessandro Faggian, Giuseppe |
author_sort | Rungatscher, Alessio |
collection | PubMed |
description | INTRODUCTION: Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA. METHODS: Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter. RESULTS: The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan. CONCLUSIONS: Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA. |
format | Online Article Text |
id | pubmed-4056352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40563522014-06-14 Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest Rungatscher, Alessio Hallström, Seth Giacomazzi, Alice Linardi, Daniele Milani, Elisabetta Tessari, Maddalena Luciani, Giovanni Battista Scarabelli, Tiziano M Mazzucco, Alessandro Faggian, Giuseppe Crit Care Research INTRODUCTION: Rewarming from deep hypothermic circulatory arrest (DHCA) produces calcium desensitization by troponin I (cTnI) phosphorylation which results in myocardial dysfunction. This study investigated the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan, a calcium sensitizer, on myocardial function after rewarming from DHCA. METHODS: Forty male Wistar rats (400 to 500 g) underwent cardiopulmonary bypass (CPB) through central cannulation and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After DHCA (20 minutes) and CPB-assisted rewarming (60 minutes) rats were randomly assigned to 60 minute intravenous infusion with levosimendan (0.2 μg/kg/min; n = 15), epinephrine (0.1 μg/kg/min; n = 15) or saline (control; n = 10). Systolic and diastolic functions were evaluated at different preloads with a conductance catheter. RESULTS: The slope of left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) recovered significantly better with levosimendan compared to epinephrine (Ees: 85 ± 9% vs 51 ± 11%, P<0.003 and PRSW: 78 ± 5% vs 48 ± 8%, P<0.005; baseline: 100%). Levosimendan but not epinephrine reduced left ventricular stiffness shown by the end-diastolic pressure-volume relationship and improved ventricular relaxation (Tau). Levosimendan preserved ATP myocardial content as well as energy charge and reduced plasma lactate concentrations. In normothermia experiments epinephrine in contrast to Levosimendan increased cTnI phosphorylation 3.5-fold. After rewarming from DHCA, cTnI phosphorylation increased 4.5-fold in the saline and epinephrine group compared to normothermia but remained unchanged with levosimendan. CONCLUSIONS: Levosimendan due to prevention of calcium desensitization by cTnI phosphorylation is more effective than epinephrine for treatment of myocardial dysfunction after rewarming from DHCA. BioMed Central 2013 2013-10-20 /pmc/articles/PMC4056352/ /pubmed/24138817 http://dx.doi.org/10.1186/cc13071 Text en Copyright © 2013 Rungatscher et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Rungatscher, Alessio Hallström, Seth Giacomazzi, Alice Linardi, Daniele Milani, Elisabetta Tessari, Maddalena Luciani, Giovanni Battista Scarabelli, Tiziano M Mazzucco, Alessandro Faggian, Giuseppe Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest |
title | Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest |
title_full | Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest |
title_fullStr | Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest |
title_full_unstemmed | Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest |
title_short | Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest |
title_sort | role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4056352/ https://www.ncbi.nlm.nih.gov/pubmed/24138817 http://dx.doi.org/10.1186/cc13071 |
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