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The Journal of Thoracic and... Jun 2021
Topics: Cardiac Surgical Procedures; Heart Ventricles; Heart-Assist Devices; Humans; Myocardial Infarction; Myocardial Reperfusion; Reperfusion Injury; Ventricular Function, Left
PubMed: 32859423
DOI: 10.1016/j.jtcvs.2020.07.078 -
Purinergic Signalling Mar 2023Purines and their derivatives, extensively distributed in the body, act as a class of extracellular signaling molecules via a rich array of receptors, also known as... (Review)
Review
Purines and their derivatives, extensively distributed in the body, act as a class of extracellular signaling molecules via a rich array of receptors, also known as purinoceptors (P1, P2X, and P2Y). They mediate multiple intracellular signal transduction pathways and participate in various physiological and pathological cell behaviors. Since the function in myocardial ischemia-reperfusion injury (MIRI), this review summarized the involvement of purinergic signal transduction in diversified pathological processes, including energy metabolism disorder, oxidative stress injury, calcium overload, inflammatory immune response, platelet aggregation, coronary vascular dysfunction, and cell necrosis and apoptosis. Moreover, increasing evidence suggests that purinergic signaling also mediates the prevention and treatment of MIRI, such as ischemic conditioning, pharmacological intervention, and some other therapies. In conclusion, this review exhibited that purinergic signaling mediates the complex processes of MIRI which shows its promising application and prospecting in the future.
Topics: Humans; Myocardial Reperfusion Injury; Heart; Signal Transduction; Coronary Vessels; Oxidative Stress
PubMed: 35254594
DOI: 10.1007/s11302-022-09856-4 -
Gaceta Medica de Mexico 2020Mexico has the highest 30-day mortality due to acute myocardial infarction (AMI), which constitutes one of the main causes of mortality in the country: 28 % versus 7.5 %...
INTRODUCTION
Mexico has the highest 30-day mortality due to acute myocardial infarction (AMI), which constitutes one of the main causes of mortality in the country: 28 % versus 7.5 % on average for the Organization for Economic Co-operation and Development member countries.
OBJECTIVE
To establish critical pathways and essential interinstitutional pharmacological strategies for the care of patients with AMI in Mexico, regardless of their socioeconomic status.
METHOD
A group of experts in AMI diagnosis and treatment, representatives of the main public health institutions in Mexico, as well as the Mexican cardiology societies, the Mexican Red Cross and representatives of the Spanish Society of Cardiology, were brought together in order to optimize strategies based on the best existing evidence.
RESULTS
An interinstitutional clinical practice guideline was designed for early diagnosis and timely treatment of AMI with ST-segment elevation, following the clinical horizon of the disease, with the proposal of algorithms that improve the prognosis of patients who attend the emergency services due to an AMI.
CONCLUSION
With these clinical practice guidelines, the group of experts proposes to universalize AMI diagnosis and treatment, regardless of patient socioeconomic status.
INTRODUCCIÓN
México tiene la mortalidad más alta a 30 días por infarto agudo de miocardio (IAM), el cual constituye una de las principales causas de mortalidad en el país: 28 % versus 7.5 % del promedio de los países de la Organización para la Cooperación y el Desarrollo Económicos.
OBJETIVO
Establecer las rutas críticas y las estrategias farmacológicas esenciales interinstitucionales para la atención de los pacientes con IAM en México, independientemente de su condición socioeconómica.
MÉTODO
Se reunió a un grupo de expertos en diagnóstico y tratamiento de IAM, representantes de las principales instituciones públicas de salud de México, así como las sociedades cardiológicas mexicanas, Cruz Roja Mexicana y representantes de la Sociedad Española de Cardiología con la finalidad de optimizar las estrategias con base en la mejor evidencia existente.
RESULTADOS
Se diseñó una guía de práctica clínica interinstitucional para el diagnóstico temprano y tratamiento oportuno del IAM con elevación del segmento ST, siguiendo el horizonte clínico de la enfermedad, con la propuesta de algoritmos que mejoren el pronóstico de los pacientes que acuden por IAM a los servicios de urgencias.
CONCLUSIÓN
Con la presente guía práctica, el grupo de expertos propone universalizar el diagnóstico y tratamiento en el IAM, independientemente de la condición socioeconómica del paciente.
Topics: Biomarkers; COVID-19; Cardiac Rehabilitation; Cause of Death; Consensus; Electrocardiography; Humans; Mexico; Myocardial Reperfusion; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Societies, Medical; Spain; Thrombolytic Therapy
PubMed: 33877123
DOI: 10.24875/GMM.M21000455 -
International Journal of Molecular... Apr 2024Myocardial ischemia/reperfusion injury is reduced by cardioprotective adaptations such as local or remote ischemic conditioning. The cardioprotective stimuli activate... (Review)
Review
Myocardial ischemia/reperfusion injury is reduced by cardioprotective adaptations such as local or remote ischemic conditioning. The cardioprotective stimuli activate signaling cascades, which converge on mitochondria and maintain the function of the organelles, which is critical for cell survival. The signaling cascades include not only extracellular molecules that activate sarcolemmal receptor-dependent or -independent protein kinases that signal at the plasma membrane or in the cytosol, but also involve kinases, which are located to or within mitochondria, phosphorylate mitochondrial target proteins, and thereby modify, e.g., respiration, the generation of reactive oxygen species, calcium handling, mitochondrial dynamics, mitophagy, or apoptosis. In the present review, we give a personal and opinionated overview of selected protein kinases, localized to/within myocardial mitochondria, and summarize the available data on their role in myocardial ischemia/reperfusion injury and protection from it. We highlight the regulation of mitochondrial function by these mitochondrial protein kinases.
Topics: Humans; Signal Transduction; Animals; Myocardial Reperfusion Injury; Mitochondria, Heart; Protein Kinases; Reactive Oxygen Species; Mitochondria
PubMed: 38674076
DOI: 10.3390/ijms25084491 -
Cardiovascular Research Mar 2021Succinate accumulates several-fold in the ischaemic heart and is then rapidly oxidized upon reperfusion, contributing to reactive oxygen species production by...
AIMS
Succinate accumulates several-fold in the ischaemic heart and is then rapidly oxidized upon reperfusion, contributing to reactive oxygen species production by mitochondria. In addition, a significant amount of the accumulated succinate is released from the heart into the circulation at reperfusion, potentially activating the G-protein-coupled succinate receptor (SUCNR1). However, the factors that determine the proportion of succinate oxidation or release, and the mechanism of this release, are not known.
METHODS AND RESULTS
To address these questions, we assessed the fate of accumulated succinate upon reperfusion of anoxic cardiomyocytes, and of the ischaemic heart both ex vivo and in vivo. The release of accumulated succinate was selective and was enhanced by acidification of the intracellular milieu. Furthermore, pharmacological inhibition, or haploinsufficiency of the monocarboxylate transporter 1 (MCT1) significantly decreased succinate efflux from the reperfused heart.
CONCLUSION
Succinate release upon reperfusion of the ischaemic heart is mediated by MCT1 and is facilitated by the acidification of the myocardium during ischaemia. These findings will allow the signalling interaction between succinate released from reperfused ischaemic myocardium and SUCNR1 to be explored.
Topics: Animals; Cells, Cultured; Disease Models, Animal; Female; Isolated Heart Preparation; Male; Metabolome; Mice, Inbred C57BL; Mice, Knockout; Mitochondria, Heart; Monocarboxylic Acid Transporters; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocytes, Cardiac; Oxidation-Reduction; Rats; Reactive Oxygen Species; Receptors, G-Protein-Coupled; Succinic Acid; Sus scrofa; Symporters; Time Factors; Mice
PubMed: 32766828
DOI: 10.1093/cvr/cvaa148 -
Med (New York, N.Y.) Jan 2024Ischemic heart disease is the greatest health burden and most frequent cause of death worldwide. Myocardial ischemia/reperfusion is the pathophysiological substrate of... (Review)
Review
Ischemic heart disease is the greatest health burden and most frequent cause of death worldwide. Myocardial ischemia/reperfusion is the pathophysiological substrate of ischemic heart disease. Improvements in prevention and treatment of ischemic heart disease have reduced mortality in developed countries over the last decades, but further progress is now stagnant, and morbidity and mortality from ischemic heart disease in developing countries are increasing. Significant problems remain to be resolved and require a better pathophysiological understanding. The present review attempts to briefly summarize the state of the art in myocardial ischemia/reperfusion research, with a view on both its coronary vascular and myocardial aspects, and to define the cutting edges where further mechanistic knowledge is needed to facilitate translation to clinical practice.
Topics: Humans; Myocardial Reperfusion Injury; Myocardial Ischemia; Myocardial Reperfusion; Myocardium
PubMed: 38218174
DOI: 10.1016/j.medj.2023.12.007 -
Basic Research in Cardiology May 2023Ischaemic heart disease, which often manifests clinically as myocardial infarction (MI), remains a major cause of mortality worldwide. Despite the development of... (Review)
Review
Ischaemic heart disease, which often manifests clinically as myocardial infarction (MI), remains a major cause of mortality worldwide. Despite the development of effective pre-clinical cardioprotective therapies, clinical translation has been disappointing. Nevertheless, the 'reperfusion injury salvage kinase' (RISK) pathway appears to be a promising target for cardioprotection. This pathway is crucial for the induction of cardioprotection by numerous pharmacological and non-pharmacological interventions, such as ischaemic conditioning. An important component of the cardioprotective effects of the RISK pathway involves the prevention of mitochondrial permeability transition pore (MPTP) opening and subsequent cardiac cell death. Here, we will review the historical perspective of the RISK pathway and focus on its interaction with mitochondria in the setting of cardioprotection.
Topics: Humans; Mitochondrial Membrane Transport Proteins; Myocardial Reperfusion Injury; Mitochondrial Permeability Transition Pore; Myocardial Ischemia; Mitochondria; Ischemic Preconditioning, Myocardial; Mitochondria, Heart
PubMed: 37233787
DOI: 10.1007/s00395-023-00992-5 -
Biomedicine & Pharmacotherapy =... Sep 2023With the growing shortage of organs, improvements in donor organ protection are needed to meet the increasing demands for transplantation. Here, the aim was to...
With the growing shortage of organs, improvements in donor organ protection are needed to meet the increasing demands for transplantation. Here, the aim was to investigate the protective effect of cinnamaldehyde against ischemia-reperfusion injury (IRI) in donor hearts exposed to prolonged cold ischemia. Donor hearts were harvested from rats pretreated with or without cinnamaldehyde, then subjected to 24 h of cold preservation and 1 h of ex vivo perfusion. Hemodynamic changes, myocardial inflammation, oxidative stress, and myocardial apoptosis were evaluated. The PI3K/AKT/mTOR pathway involved in the cardioprotective effects of cinnamaldehyde was explored through RNA sequencing and western blot analysis. Intriguingly, cinnamaldehyde pretreatment remarkably improved cardiac function through increasing coronary flow, left ventricular systolic pressure, +dp/dt, and -dp/dt, decreasing coronary vascular resistance and left ventricular end-diastolic pressure. Moreover, our findings indicated that cinnamaldehyde pretreatment protected the heart from IRI by alleviating myocardial inflammation, attenuating oxidative stress, and reducing myocardial apoptosis. Further studies showed that the PI3K/AKT/mTOR pathway was activated after cinnamaldehyde treatment during IRI. The protective effects of cinnamaldehyde were abolished by LY294002. In conclusion, cinnamaldehyde pretreatment alleviated IRI in donor hearts suffering from prolonged cold ischemia. Cinnamaldehyde exerted cardioprotective effects through the activation of the PI3K/AKT/mTOR pathway.
Topics: Rats; Animals; Humans; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Heart Transplantation; Rats, Sprague-Dawley; Myocardial Reperfusion Injury; Tissue Donors; TOR Serine-Threonine Kinases; Apoptosis; Inflammation
PubMed: 37385214
DOI: 10.1016/j.biopha.2023.114867 -
Molecules (Basel, Switzerland) Jul 2020Myocardial infarction (MI) is a leading cause of morbidity and mortality across the world. It manifests as an imbalance between blood demand and blood delivery in the... (Review)
Review
Myocardial infarction (MI) is a leading cause of morbidity and mortality across the world. It manifests as an imbalance between blood demand and blood delivery in the myocardium, which leads to cardiac ischemia and myocardial necrosis. While it is not easy to identify the first pathogenic cause of MI, the consequences are characterized by ischemia, chronic inflammation, and tissue degeneration. A poor MI prognosis is associated with extensive cardiac remodeling. A loss of viable cardiomyocytes is replaced with fibrosis, which reduces heart contractility and heart function. Recent advances have given rise to the concept of natural polyphenols. These bioactive compounds have been studied for their pharmacological properties and have proven successful in the treatment of cardiovascular diseases. Studies have focused on their various bioactivities, such as their antioxidant and anti-inflammatory effects and free radical scavenging. In this review, we summarized the effects and benefits of polyphenols on the cardiovascular injury, particularly on the treatment of myocardial infarction in animal and human studies.
Topics: Animals; Antioxidants; Cardiotonic Agents; Humans; Myocardial Reperfusion Injury; Polyphenols
PubMed: 32751587
DOI: 10.3390/molecules25153469 -
Biomedicine & Pharmacotherapy =... Sep 2023The current study intended to delve into the mechanisms of dexmedetomidine (Dex) in regulating myocardial pyroptosis against myocardial ischemia/reperfusion injury...
The current study intended to delve into the mechanisms of dexmedetomidine (Dex) in regulating myocardial pyroptosis against myocardial ischemia/reperfusion injury (MIRI). The rat MIRI models were induced by ligation/release of the coronary artery in vivo and Langendorff perfusion ex vivo. Hemodynamic parameters, infarction sizes, and histopathological changes were assessed to understand the effects of Dex on MIRI. We explored the mechanisms through functional experiments on an H9c2 cell hypoxia/reoxygenation (H/R) model. Cell viability and apoptosis were evaluated using cell counting kit 8 (CCK-8) and AV/PI dual staining respectively. The expressions of miR-665 and MEF2D mRNA were detected by qRT-PCR. Western blot was employed to determine the expression levels of pyroptosis- and signaling pathway- related proteins. The interplays between miR-665 and MEF2D were validated by Dual-luciferase reporter assays. Our findings indicated that Dex preconditioning dramatically attenuated hemodynamic derangements, infarct size, and histopathological damage in rats undergoing MIRI. Dex markedly augmented cell viability, while suppressing cell apoptosis and expressions of NLRP3, cleaved-caspase-1, ASC, GSDMD, IL-1β, and IL-18 in H9c2 cells subjected to H/R injury. MiR-665 was significantly upregulated, MEF2D and Nrf2 downregulated following H/R, whereas Dex preconditioning reversed these changes. MEF2D was validated to be a target gene of miR-665. Overexpression of miR-665 decreased the expression of MEF2D and blunted the protective effects of Dex in H9c2 cells. Moreover, the functional rescue experiment further verified that Dex regulated MEF2D/Nrf2 pathway via miR-665. In conclusion, Dex mitigates MIRI through inhibiting pyroptosis via regulating miR-665/MEF2D/Nrf2 axis.
Topics: Rats; Animals; Myocardial Reperfusion Injury; Pyroptosis; Dexmedetomidine; NF-E2-Related Factor 2; Cell Line; MicroRNAs; Apoptosis; Myocytes, Cardiac; Reperfusion Injury; MEF2 Transcription Factors
PubMed: 37549462
DOI: 10.1016/j.biopha.2023.115255