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The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading

BACKGROUND: It remains unclear whether the Rho-kinase (ROCK) inhibition in combination with mechanical circulatory support (MCS) had a synergic protective effect on myocardial ischemia (MI)/reperfusion injury in therapeutic strategies for acute myocardial infarction (AMI). We report the results of a...

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Autores principales: Miyahara, Shunsuke, Jenke, Alexander, Yazdanyar, Mariam, Kistner, Julia, Immohr, Moritz Benjamin, Sugimura, Yukiharu, Aubin, Hug, Kamiya, Hiroyuki, Okita, Yutaka, Lichtenberg, Artur, Akhyari, Payam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513506/
https://www.ncbi.nlm.nih.gov/pubmed/35837687
http://dx.doi.org/10.1177/02184923221114457
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author Miyahara, Shunsuke
Jenke, Alexander
Yazdanyar, Mariam
Kistner, Julia
Immohr, Moritz Benjamin
Sugimura, Yukiharu
Aubin, Hug
Kamiya, Hiroyuki
Okita, Yutaka
Lichtenberg, Artur
Akhyari, Payam
author_facet Miyahara, Shunsuke
Jenke, Alexander
Yazdanyar, Mariam
Kistner, Julia
Immohr, Moritz Benjamin
Sugimura, Yukiharu
Aubin, Hug
Kamiya, Hiroyuki
Okita, Yutaka
Lichtenberg, Artur
Akhyari, Payam
author_sort Miyahara, Shunsuke
collection PubMed
description BACKGROUND: It remains unclear whether the Rho-kinase (ROCK) inhibition in combination with mechanical circulatory support (MCS) had a synergic protective effect on myocardial ischemia (MI)/reperfusion injury in therapeutic strategies for acute myocardial infarction (AMI). We report the results of an approach using a rat model consisting of a miniaturized cardiopulmonary bypass (CPB) and AMI. METHODS: A total of 25 male Wistar rats were randomized into 5 groups: (1) Sham: a suture was passed under the left anterior descending artery (LAD) creating no MI. A vehicle solution (0.9% saline) was injected intraperitoneally. (2) Myocardial ischemia (MI) + vehicle (MI + V): LAD was ligated for 30 min and reperfused for 120 min, followed by administration of vehicle solution. (3) MI + fasudil (MI + F): the work sequence of group 2, but the selective ROCK inhibitor fasudil (10 mg/kg) was administered instead. (4) MI + V + CPB: CPB was initiated 15 min after the ligation of the LAD to the end of the reperfusion, in addition to the work sequence in group 2. (5) In the MI + F + CPB group, the work sequence of group 4, but with fasudil administration (10 mg/kg). RESULTS: Measurements of cardiac function through conductance catheter indicated that the drop of + dP/dt after reperfusion was moderately limited in MI + F + CPB (vs. MI + V, dP/dt p = 0.22). The preload recruitable stroke work was moderately improved in the MI + F + CPB (p = 0.23) compared with the corresponding control animals (MI + V). Phosphorylated protein kinase B expression in the MI + V + CPB and MI + F + CPB was higher than that in MI + V (p = 0.33). CONCLUSION: Therefore, fasudil administration with MCS resulted in a moderately better left ventricular performance.
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spelling pubmed-95135062022-09-28 The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading Miyahara, Shunsuke Jenke, Alexander Yazdanyar, Mariam Kistner, Julia Immohr, Moritz Benjamin Sugimura, Yukiharu Aubin, Hug Kamiya, Hiroyuki Okita, Yutaka Lichtenberg, Artur Akhyari, Payam Asian Cardiovasc Thorac Ann Original Articles BACKGROUND: It remains unclear whether the Rho-kinase (ROCK) inhibition in combination with mechanical circulatory support (MCS) had a synergic protective effect on myocardial ischemia (MI)/reperfusion injury in therapeutic strategies for acute myocardial infarction (AMI). We report the results of an approach using a rat model consisting of a miniaturized cardiopulmonary bypass (CPB) and AMI. METHODS: A total of 25 male Wistar rats were randomized into 5 groups: (1) Sham: a suture was passed under the left anterior descending artery (LAD) creating no MI. A vehicle solution (0.9% saline) was injected intraperitoneally. (2) Myocardial ischemia (MI) + vehicle (MI + V): LAD was ligated for 30 min and reperfused for 120 min, followed by administration of vehicle solution. (3) MI + fasudil (MI + F): the work sequence of group 2, but the selective ROCK inhibitor fasudil (10 mg/kg) was administered instead. (4) MI + V + CPB: CPB was initiated 15 min after the ligation of the LAD to the end of the reperfusion, in addition to the work sequence in group 2. (5) In the MI + F + CPB group, the work sequence of group 4, but with fasudil administration (10 mg/kg). RESULTS: Measurements of cardiac function through conductance catheter indicated that the drop of + dP/dt after reperfusion was moderately limited in MI + F + CPB (vs. MI + V, dP/dt p = 0.22). The preload recruitable stroke work was moderately improved in the MI + F + CPB (p = 0.23) compared with the corresponding control animals (MI + V). Phosphorylated protein kinase B expression in the MI + V + CPB and MI + F + CPB was higher than that in MI + V (p = 0.33). CONCLUSION: Therefore, fasudil administration with MCS resulted in a moderately better left ventricular performance. SAGE Publications 2022-07-15 2022-10 /pmc/articles/PMC9513506/ /pubmed/35837687 http://dx.doi.org/10.1177/02184923221114457 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Articles
Miyahara, Shunsuke
Jenke, Alexander
Yazdanyar, Mariam
Kistner, Julia
Immohr, Moritz Benjamin
Sugimura, Yukiharu
Aubin, Hug
Kamiya, Hiroyuki
Okita, Yutaka
Lichtenberg, Artur
Akhyari, Payam
The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading
title The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading
title_full The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading
title_fullStr The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading
title_full_unstemmed The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading
title_short The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading
title_sort combination approach with rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: rho-kinase inhibition and ventricular unloading
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513506/
https://www.ncbi.nlm.nih.gov/pubmed/35837687
http://dx.doi.org/10.1177/02184923221114457
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