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Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
by
Hollmann, Markus W.
, van den Brom, Charissa E.
, Huhn, Ragnar
, Preckel, Benedikt
, Wang, Qian
, Zuurbier, Coert J.
, Torregroza, Carolin
, Weber, Nina C.
in
Acidosis
/ Adenosine triphosphate
/ Animal models
/ Apoptosis
/ Calcium (mitochondrial)
/ Calcium permeability
/ Cardiac conditioning
/ Cardiomyocytes
/ cardioprotection
/ Care and treatment
/ Comorbidity
/ Cytochrome
/ drug development
/ Endoplasmic reticulum
/ Endothelium
/ Glycogen
/ Heart
/ Heart cells
/ Ischemia
/ ischemia-reperfusion injury
/ Membrane permeability
/ Mitochondria
/ Mitochondrial permeability transition pore
/ Myocardial ischemia
/ Nitric oxide
/ Oxidation
/ Oxidative stress
/ Permeability
/ Phosphorylation
/ Physiological aspects
/ Reactive oxygen species
/ Reperfusion
/ Review
2023
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Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
by
Hollmann, Markus W.
, van den Brom, Charissa E.
, Huhn, Ragnar
, Preckel, Benedikt
, Wang, Qian
, Zuurbier, Coert J.
, Torregroza, Carolin
, Weber, Nina C.
in
Acidosis
/ Adenosine triphosphate
/ Animal models
/ Apoptosis
/ Calcium (mitochondrial)
/ Calcium permeability
/ Cardiac conditioning
/ Cardiomyocytes
/ cardioprotection
/ Care and treatment
/ Comorbidity
/ Cytochrome
/ drug development
/ Endoplasmic reticulum
/ Endothelium
/ Glycogen
/ Heart
/ Heart cells
/ Ischemia
/ ischemia-reperfusion injury
/ Membrane permeability
/ Mitochondria
/ Mitochondrial permeability transition pore
/ Myocardial ischemia
/ Nitric oxide
/ Oxidation
/ Oxidative stress
/ Permeability
/ Phosphorylation
/ Physiological aspects
/ Reactive oxygen species
/ Reperfusion
/ Review
2023
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Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
by
Hollmann, Markus W.
, van den Brom, Charissa E.
, Huhn, Ragnar
, Preckel, Benedikt
, Wang, Qian
, Zuurbier, Coert J.
, Torregroza, Carolin
, Weber, Nina C.
in
Acidosis
/ Adenosine triphosphate
/ Animal models
/ Apoptosis
/ Calcium (mitochondrial)
/ Calcium permeability
/ Cardiac conditioning
/ Cardiomyocytes
/ cardioprotection
/ Care and treatment
/ Comorbidity
/ Cytochrome
/ drug development
/ Endoplasmic reticulum
/ Endothelium
/ Glycogen
/ Heart
/ Heart cells
/ Ischemia
/ ischemia-reperfusion injury
/ Membrane permeability
/ Mitochondria
/ Mitochondrial permeability transition pore
/ Myocardial ischemia
/ Nitric oxide
/ Oxidation
/ Oxidative stress
/ Permeability
/ Phosphorylation
/ Physiological aspects
/ Reactive oxygen species
/ Reperfusion
/ Review
2023
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Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
Journal Article
Pharmacological Cardioprotection against Ischemia Reperfusion Injury—The Search for a Clinical Effective Therapy
2023
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Overview
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 (∆GATP, Na+, Ca2+, pH, glycogen, succinate, glucose-6-phosphate, mitoHKII, acylcarnitines, BH4, and NAD+). These compounds all precipitate common end-effector mechanisms of IRI, such as reactive oxygen species (ROS) generation, Ca2+ 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.
Publisher
MDPI AG,MDPI
Subject
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