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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
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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. |
format | Online Article Text |
id | pubmed-9513506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
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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