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Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy

Pharmacological conditioning aims to protect the heart from myocardial ischemia-reperfusion injury (IRI). Despite extensive research in this area, today, a significant gap remains between experimental findings and clinical practice. This review provides an update on recent developments in pharmacolo...

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Autores principales: Wang, Qian, Zuurbier, Coert J., Huhn, Ragnar, Torregroza, Carolin, Hollmann, Markus W., Preckel, Benedikt, van den Brom, Charissa E., Weber, Nina C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217104/
https://www.ncbi.nlm.nih.gov/pubmed/37408266
http://dx.doi.org/10.3390/cells12101432
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author Wang, Qian
Zuurbier, Coert J.
Huhn, Ragnar
Torregroza, Carolin
Hollmann, Markus W.
Preckel, Benedikt
van den Brom, Charissa E.
Weber, Nina C.
author_facet Wang, Qian
Zuurbier, Coert J.
Huhn, Ragnar
Torregroza, Carolin
Hollmann, Markus W.
Preckel, Benedikt
van den Brom, Charissa E.
Weber, Nina C.
author_sort Wang, Qian
collection PubMed
description Pharmacological conditioning aims to protect the heart from myocardial ischemia-reperfusion injury (IRI). Despite extensive research in this area, today, a significant gap remains between experimental findings and clinical practice. This review provides an update on recent developments in pharmacological conditioning in the experimental setting and summarizes the clinical evidence of these cardioprotective strategies in the perioperative setting. We start describing the crucial cellular processes during ischemia and reperfusion that drive acute IRI through changes in critical compounds (∆G(ATP), Na(+), Ca(2+), pH, glycogen, succinate, glucose-6-phosphate, mitoHKII, acylcarnitines, BH(4), and NAD(+)). These compounds all precipitate common end-effector mechanisms of IRI, such as reactive oxygen species (ROS) generation, Ca(2+) overload, and mitochondrial permeability transition pore opening (mPTP). We further discuss novel promising interventions targeting these processes, with emphasis on cardiomyocytes and the endothelium. The limited translatability from basic research to clinical practice is likely due to the lack of comorbidities, comedications, and peri-operative treatments in preclinical animal models, employing only monotherapy/monointervention, and the use of no-flow (always in preclinical models) versus low-flow ischemia (often in humans). Future research should focus on improved matching between preclinical models and clinical reality, and on aligning multitarget therapy with optimized dosing and timing towards the human condition.
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spelling pubmed-102171042023-05-27 Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy Wang, Qian Zuurbier, Coert J. Huhn, Ragnar Torregroza, Carolin Hollmann, Markus W. Preckel, Benedikt van den Brom, Charissa E. Weber, Nina C. Cells Review Pharmacological conditioning aims to protect the heart from myocardial ischemia-reperfusion injury (IRI). Despite extensive research in this area, today, a significant gap remains between experimental findings and clinical practice. This review provides an update on recent developments in pharmacological conditioning in the experimental setting and summarizes the clinical evidence of these cardioprotective strategies in the perioperative setting. We start describing the crucial cellular processes during ischemia and reperfusion that drive acute IRI through changes in critical compounds (∆G(ATP), Na(+), Ca(2+), pH, glycogen, succinate, glucose-6-phosphate, mitoHKII, acylcarnitines, BH(4), and NAD(+)). These compounds all precipitate common end-effector mechanisms of IRI, such as reactive oxygen species (ROS) generation, Ca(2+) overload, and mitochondrial permeability transition pore opening (mPTP). We further discuss novel promising interventions targeting these processes, with emphasis on cardiomyocytes and the endothelium. The limited translatability from basic research to clinical practice is likely due to the lack of comorbidities, comedications, and peri-operative treatments in preclinical animal models, employing only monotherapy/monointervention, and the use of no-flow (always in preclinical models) versus low-flow ischemia (often in humans). Future research should focus on improved matching between preclinical models and clinical reality, and on aligning multitarget therapy with optimized dosing and timing towards the human condition. MDPI 2023-05-20 /pmc/articles/PMC10217104/ /pubmed/37408266 http://dx.doi.org/10.3390/cells12101432 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wang, Qian
Zuurbier, Coert J.
Huhn, Ragnar
Torregroza, Carolin
Hollmann, Markus W.
Preckel, Benedikt
van den Brom, Charissa E.
Weber, Nina C.
Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
title Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
title_full Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
title_fullStr Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
title_full_unstemmed Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
title_short Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
title_sort pharmacological cardioprotection against ischemia reperfusion injury—the search for a clinical effective therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10217104/
https://www.ncbi.nlm.nih.gov/pubmed/37408266
http://dx.doi.org/10.3390/cells12101432
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