The role of aldosterone inhibitors in cardiac ischemia–reperfusion injury

Dragasevic, Nevena; Jakovljević, Vladimir; Živković, Vladimir; Draginić, Nevena; Andjić, Marijana; Bolevich, Sergey; Jovic, Slavoljub

doi:10.1139/cjpp-2020-0276

Cited by 4 publications

(4 citation statements)

References 96 publications

(87 reference statements)

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“…Both leupeptin and compound MDL28170 (inhibitors of matrix metalloproteinases) were observed to prevent I/R injury by depressing the activation of proteolytic enzymes in the heart [ 26 , 102 , 103 ]. Furthermore, various aldosterone receptor antagonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors have been observed to attenuate I/R injury as well as infarct size due to myocardial infarction by multiple mechanisms including inflammation and oxidative stress [ 104 , 105 ]. Because of the multifactorial basis of I/R injury, a wide variety of drugs such as cyclosporin, colchicine, tocilizumab, glucagon-like peptide 1 antagonist and modulators of different protein kinases (acting at different target sites) have been demonstrated to limit myocardial infarct size as well as prevent cardiac arrhythmias, cellular necrosis, apoptosis, and metabolic defects [ 99 , 106 , 107 , 108 ].…”

Section: Pharmacotherapy Of I/r Injury To the Heartmentioning

confidence: 99%

Role of Oxidative Stress in Cardiac Dysfunction and Subcellular Defects Due to Ischemia-Reperfusion Injury

et al. 2022

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Ischemia-reperfusion (I/R) injury is well-known to be associated with impaired cardiac function, massive arrhythmias, marked alterations in cardiac metabolism and irreversible ultrastructural changes in the heart. Two major mechanisms namely oxidative stress and intracellular Ca2+-overload are considered to explain I/R-induced injury to the heart. However, it is becoming apparent that oxidative stress is the most critical pathogenic factor because it produces myocardial abnormalities directly or indirectly for the occurrence of cardiac damage. Furthermore, I/R injury has been shown to generate oxidative stress by promoting the formation of different reactive oxygen species due to defects in mitochondrial function and depressions in both endogenous antioxidant levels as well as regulatory antioxidative defense systems. It has also been demonstrated to adversely affect a wide variety of metabolic pathways and targets in cardiomyocytes, various resident structures in myocardial interstitium, as well as circulating neutrophils and leukocytes. These I/R-induced alterations in addition to myocardial inflammation may cause cell death, fibrosis, inflammation, Ca2+-handling abnormalities, activation of proteases and phospholipases, as well as subcellular remodeling and depletion of energy stores in the heart. Analysis of results from isolated hearts perfused with or without some antioxidant treatments before subjecting to I/R injury has indicated that cardiac dysfunction is associated with the development of oxidative stress, intracellular Ca2+-overload and protease activation. In addition, changes in the sarcolemma and sarcoplasmic reticulum Ca2+-handling, mitochondrial oxidative phosphorylation as well as myofibrillar Ca2+-ATPase activities in I/R hearts were attenuated by pretreatment with antioxidants. The I/R-induced alterations in cardiac function were simulated upon perfusing the hearts with oxyradical generating system or oxidant. These observations support the view that oxidative stress may be intimately involved in inducing intracellular Ca2+-overload, protease activation, subcellular remodeling, and cardiac dysfunction as a consequence of I/R injury to the heart.

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Section: Pharmacotherapy Of I/r Injury To the Heartmentioning

confidence: 99%

Role of Oxidative Stress in Cardiac Dysfunction and Subcellular Defects Due to Ischemia-Reperfusion Injury

et al. 2022

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“…This leads to inflammation, oxidative stress, and apoptosis in the cardiac tissues [ 104 ]. MR antagonists have proven effective in limiting the ischemia/reperfusion-induced tissue damage and, correspondingly, the infarction zone [ 105 ]. Fraccarollo et al showed that a cardiomyocytespecific deletion of the MR in mice could reduce post-myocardial infarction (post-MI) cardiac remodeling [ 106 ].…”

Section: Over-active Mr In the Absence Of Elevated Aldosterone Levelsmentioning

confidence: 99%

Importance of Micromilieu for Pathophysiologic Mineralocorticoid Receptor Activity—When the Mineralocorticoid Receptor Resides in the Wrong Neighborhood

Griesler

Schuelke

Uhlig

et al. 2022

IJMS

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The mineralocorticoid receptor (MR) is a member of the steroid receptor family and acts as a ligand-dependent transcription factor. In addition to its classical effects on water and electrolyte balance, its involvement in the pathogenesis of cardiovascular and renal diseases has been the subject of research for several years. The molecular basis of the latter has not been fully elucidated, but an isolated increase in the concentration of the MR ligand aldosterone or MR expression does not suffice to explain long-term pathologic actions of the receptor. Several studies suggest that MR activity and signal transduction are modulated by the surrounding microenvironment, which therefore plays an important role in MR pathophysiological effects. Local changes in micromilieu, including hypoxia, ischemia/reperfusion, inflammation, radical stress, and aberrant salt or glucose concentrations affect MR activation and therefore may influence the probability of unphysiological MR actions. The surrounding micromilieu may modulate genomic MR activity either by causing changes in MR expression or MR activity; for example, by inducing posttranslational modifications of the MR or novel interaction with coregulators, DNA-binding sites, or non-classical pathways. This should be considered when developing treatment options and strategies for prevention of MR-associated diseases.

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“…Although the restoration of blood (reperfusion) to an ischemic heart is essential in order to save the myocardium, it can paradoxically cause irreversible myocardial damage termed “ischemia–reperfusion (I–R) injury”. Reperfusion after an ischemic episode may result in cardiomyocyte dysfunction caused by the production of reactive oxygen species (ROS), intracellular and mitochondrial Ca 2+ overload, and the accumulation of inflammatory cells [ 5 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Cardioplegia in Open Heart Surgery: Age Matters

Bradić

Andjić

Jeremić

et al. 2023

JCM

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Introduction: Cardioplegia is a pharmacological approach essential for the protection of the heart from ischemia–reperfusion (I–R) injury. Over the years, numerous cardioplegic solutions have been developed, with each cardioplegic approach having its advantages and disadvantages. Cardioplegic solutions can be divided into crystalloid and blood cardioplegic solutions, and an experienced surgeon chooses the type of solution based on the individual needs of patients in order to provide optimal heart protection. Importantly, the pediatric immature myocardium is structurally, physiologically, and metabolically different from the adult heart, and consequently its needs to achieve cardioplegic arrest strongly differ. Therefore, the present review aimed to provide a summary of the cardioplegic solutions available to pediatric patients with a special focus on emphasizing differences in heart injury after various cardioplegic solutions, the dosing strategies, and regimens. Material and methods: The PubMed database was searched using the terms cardioplegia, I–R, and pediatric population, and studies that investigated the influence of cardioplegic strategies on markers of cardiac muscle damage were further analyzed in this review. Conclusions: A large body of evidence suggested more prominent benefits achieved with blood compared to those with crystalloid cardioplegia in pediatric myocardium preservation. However, standardized and uniform protocols have not been established so far, and an experienced surgeon chooses the type of cardioplegia solution based on the individual needs of patients, while the severity of myocardial damage strongly depends on the type and duration of the surgical procedure, overall patient condition, and presence of comorbidities, etc.

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The role of aldosterone inhibitors in cardiac ischemia–reperfusion injury

Cited by 4 publications

References 96 publications

Role of Oxidative Stress in Cardiac Dysfunction and Subcellular Defects Due to Ischemia-Reperfusion Injury

Role of Oxidative Stress in Cardiac Dysfunction and Subcellular Defects Due to Ischemia-Reperfusion Injury

Importance of Micromilieu for Pathophysiologic Mineralocorticoid Receptor Activity—When the Mineralocorticoid Receptor Resides in the Wrong Neighborhood

Cardioplegia in Open Heart Surgery: Age Matters

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