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Cardiovascular Drugs and Therapy Aug 2023Recombinant apyrase (AZD3366) increases adenosine production and ticagrelor inhibits adenosine reuptake. We investigated whether intravenous AZD3366 before reperfusion...
PURPOSE
Recombinant apyrase (AZD3366) increases adenosine production and ticagrelor inhibits adenosine reuptake. We investigated whether intravenous AZD3366 before reperfusion reduces myocardial infarct size (IS) and whether AZD3366 and ticagrelor have additive effects.
METHODS
Sprague-Dawley rats underwent 30 min ischemia. At 25 min of ischemia, animals received intravenous AZD3366 or vehicle. Additional animals received intravenous CGS15943 (an adenosine receptor blocker) or intraperitoneal ticagrelor. At 24 h reperfusion, IS was assessed by triphenyltetrazolium chloride. Other rats were subjected to 30 min ischemia followed by 1 h or 24 h reperfusion. Myocardial samples were assessed for adenosine levels, RT-PCR, and immunoblotting.
RESULTS
AZD3366 and ticagrelor reduced IS. The protective effect was blocked by CGS15943. The effect of AZD3366 + ticagrelor was significantly greater than AZD3366. One hour after infarction, myocardial adenosine levels significantly increased with AZD3366, but not with ticagrelor. In contrast, 24 h after infarction, adenosine levels were equally increased by AZD3366 and ticagrelor, and levels were higher in the AZD3366 + ticagrelor group. One hour after reperfusion, AZD3366 and ticagrelor equally attenuated the increase in interleukin-15 (an early inflammatory marker after ischemic cell death) levels, and their combined effects were additive. AZD3366, but not ticagrelor, significantly attenuated the increase in RIP1, RIP3, and P-MLKL (markers of necroptosis) 1 h after reperfusion. AZD3366, but not ticagrelor, significantly attenuated the increase in IL-6 and GSDMD-N (markers of pyroptosis) 1 h after reperfusion. At 24 h of reperfusion, both agents equally attenuated the increase in these markers, and their effects were additive.
CONCLUSIONS
AZD3366 attenuated inflammation, necrosis, necroptosis, and pyroptosis and limited IS. The effects of AZD3366 and ticagrelor were additive.
Topics: Rats; Animals; Myocardial Reperfusion Injury; Apyrase; Rats, Sprague-Dawley; Ticagrelor; Adenosine
PubMed: 35192075
DOI: 10.1007/s10557-022-07329-9 -
Biomedicine & Pharmacotherapy =... May 2022Patients with ischemic heart disease receiving reperfusion therapy still need to face left ventricular remodeling and heart failure after myocardial infarction.... (Review)
Review
Patients with ischemic heart disease receiving reperfusion therapy still need to face left ventricular remodeling and heart failure after myocardial infarction. Reperfusion itself paradoxically leads to further cardiomyocyte death and systolic dysfunction. Ischemia/reperfusion (I/R) injury can eliminate the benefits of reperfusion therapy in patients and causes secondary myocardial injury. Mitochondrial dysfunction and structural disorder are the basic driving force of I/R injury. We summarized the basic relationship and potential mechanisms of mitochondrial injury in the development of I/R injury. Subsequently, this review summarized the natural products (NPs) that have been proven to targeting mitochondrial therapeutic effects during I/R injury in recent years and related cellular signal transduction pathways. We found that these NPs mainly protected the structural integrity of mitochondria and improve dysfunction, such as reducing mitochondrial division and fusion abnormalities, improving mitochondrial Ca overload and inhibiting reactive oxygen species overproduction, thereby playing a role in protecting cardiomyocytes during I/R injury. This data would deepen the understanding of I/R-induced mitochondrial pathological process and suggested that NPs are expected to be transformed into potential therapies targeting mitochondria.
Topics: Biological Products; Humans; Mitochondria; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Reactive Oxygen Species; Reperfusion
PubMed: 35366532
DOI: 10.1016/j.biopha.2022.112893 -
Journal of the American College of... Jun 2024Despite impressive improvements in the care of patients with ST-segment elevation myocardial infarction, mortality remains high. Reperfusion is necessary for myocardial... (Review)
Review
Despite impressive improvements in the care of patients with ST-segment elevation myocardial infarction, mortality remains high. Reperfusion is necessary for myocardial salvage, but the abrupt return of flow sets off a cascade of injurious processes that can lead to further necrosis. This has been termed myocardial ischemia-reperfusion injury and is the subject of this review. The pathologic and molecular bases for myocardial ischemia-reperfusion injury are increasingly understood and include injury from reactive oxygen species, inflammation, calcium overload, endothelial dysfunction, and impaired microvascular flow. A variety of pharmacologic strategies have been developed that have worked well in preclinical models and some have shown promise in the clinical setting. In addition, there are newer mechanical approaches including mechanical unloading of the heart prior to reperfusion that are in current clinical trials.
Topics: Humans; Myocardial Reperfusion Injury; Myocardial Infarction; Myocardial Reperfusion; ST Elevation Myocardial Infarction
PubMed: 38811097
DOI: 10.1016/j.jacc.2024.02.056 -
Circulation. Cardiovascular... Aug 2021Myocardial reperfusion injury-triggered by an inevitable inflammatory response after reperfusion-may undo a considerable part of the myocardial salvage achieved through... (Review)
Review
Myocardial reperfusion injury-triggered by an inevitable inflammatory response after reperfusion-may undo a considerable part of the myocardial salvage achieved through timely percutaneous coronary intervention in patients with acute myocardial infarction. Because infarct size is strongly correlated to mortality and risk of heart failure, the importance of endeavors for cardioprotective therapies to attenuate myocardial reperfusion injury and decrease infarct size remains undisputed. Myocardial reperfusion injury is the result of several complex nonlinear phenomena, and for a therapy to be effective, it should act on multiple targets involved in this injury. In this regard, hypothermia remains a promising treatment despite a number of negative randomized controlled trials in humans with acute myocardial infarction so far. To turn the tide for hypothermia in patients with acute myocardial infarction, sophisticated solutions for important limitations of systemic hypothermia should continue to be developed. In this review, we provide a comprehensive overview of the pathophysiology and clinical expression of myocardial reperfusion injury and discuss the current status and possible future of hypothermia for cardioprotection in patients with acute myocardial infarction.
Topics: Humans; Hypothermia; Hypothermia, Induced; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Percutaneous Coronary Intervention
PubMed: 34266310
DOI: 10.1161/CIRCINTERVENTIONS.120.010326 -
Drug Delivery Dec 2024Acute myocardial infarction, characterized by high morbidity and mortality, has now become a serious health hazard for human beings. Conventional surgical interventions... (Review)
Review
Acute myocardial infarction, characterized by high morbidity and mortality, has now become a serious health hazard for human beings. Conventional surgical interventions to restore blood flow can rapidly relieve acute myocardial ischemia, but the ensuing myocardial ischemia-reperfusion injury (MI/RI) and subsequent heart failure have become medical challenges that researchers have been trying to overcome. The pathogenesis of MI/RI involves several mechanisms, including overproduction of reactive oxygen species, abnormal mitochondrial function, calcium overload, and other factors that induce cell death and inflammatory responses. These mechanisms have led to the exploration of antioxidant and inflammation-modulating therapies, as well as the development of myocardial protective factors and stem cell therapies. However, the short half-life, low bioavailability, and lack of targeting of these drugs that modulate these pathological mechanisms, combined with liver and spleen sequestration and continuous washout of blood flow from myocardial sites, severely compromise the expected efficacy of clinical drugs. To address these issues, employing conventional nanocarriers and integrating them with contemporary biomimetic nanocarriers, which rely on passive targeting and active targeting through precise modifications, can effectively prolong the duration of therapeutic agents within the body, enhance their bioavailability, and augment their retention at the injured myocardium. Consequently, these approaches significantly enhance therapeutic effectiveness while minimizing toxic side effects. This article reviews current drug delivery systems used for MI/RI, aiming to offer a fresh perspective on treating this disease.
Topics: Humans; Myocardial Reperfusion Injury; Myocardium; Myocardial Infarction; Cell Death; Antioxidants
PubMed: 38147501
DOI: 10.1080/10717544.2023.2298514 -
Biological & Pharmaceutical Bulletin Apr 2023This study investigated whether pretreatment with puerarin could alleviate myocardial ischemia/reperfusion (I/R) injury in a cardiomyocyte oxygen-glucose deprivation and...
This study investigated whether pretreatment with puerarin could alleviate myocardial ischemia/reperfusion (I/R) injury in a cardiomyocyte oxygen-glucose deprivation and reoxygenation (OGD/R) model and in a mouse I/R injury model. For in vitro experiments, H9C2 cells were divided into control, erastin, OGD/R, OGD/R + puerarin, and OGD/R + ferrostatin (Fer)-1 groups. Parameters related to ferroptosis included levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), ATP, reactive oxygen species (ROS), glutathione (GSH), prostaglandin endoperoxide synthase (Ptgs) 2 mRNA, glutathione peroxidase (GPX) 4 protein and iron. In H9C2 cells, puerarin or Fer-1 pretreatment reduced ferroptosis, as indicated by decreased ROS and increased GSH, ATP levels. In vivo, wild-type mice were randomly divided into sham, I/R + vehicle, I/R + puerarin, and IR + Fer-1 groups. The I/R model was established by 30 min of left anterior descending artery occlusion followed by 24 h of reperfusion. Pretreatment with puerarin or Fer-1 significantly reduced infarct size in I/R mice, and decreased the activities of Myeloperoxidase (MPO) and cardiac enzymes such as creatine kinase MB isoenzyme (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) compared to those in the vehicle-treated group. Puerarin also reduced the production of MDA and 4-HNE, reduced the mRNA expression of Ptgs2 mRNA, and increased GPX4 protein expression. These results showed that puerarin exerted protective effects against myocardial I/R injury by inhibiting ferroptosis and inflammation, and therefore may have therapeutic potential for treatment of acute myocardial infarction.
Topics: Mice; Animals; Myocardial Reperfusion Injury; Reactive Oxygen Species; Ferroptosis; Reperfusion Injury; Glutathione; RNA, Messenger; Adenosine Triphosphate
PubMed: 36696989
DOI: 10.1248/bpb.b22-00174 -
European Heart Journal. Acute... Jun 2020
Topics: Disease Management; Humans; Myocardial Reperfusion Injury; Myocardial Revascularization; ST Elevation Myocardial Infarction
PubMed: 33025813
DOI: 10.1177/2048872620934298 -
BMJ Open Sep 2022ST-segment elevation myocardial infarction (STEMI) is the most severe clinical form of acute myocardial infarction, for which the current treatment consists of effective...
INTRODUCTION
ST-segment elevation myocardial infarction (STEMI) is the most severe clinical form of acute myocardial infarction, for which the current treatment consists of effective and timely myocardial reperfusion (within 12 hours of symptom onset). However, between 10% and 15% of patients with STEMI arrive at hospital facilities 12 hours after the onset of symptoms (late presentation). Therefore, the objective of the present study will be to determine if late revascularisation (12-72 hours after the onset of symptoms) affects the indicators of cardiovascular mortality, reinfarction, recurrent infarction, hospitalisation for heart failure and post infarction angina compared with no late revascularisation in patients with STEMI.
METHODS AND ANALYSIS
A systematic literature search of PubMed, The Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Scopus and Global Health will be conducted. Publications in English, Portuguese or Spanish that report the clinical results of primary percutaneous revascularisation (primary PCI) in adult patients with STEMI 12-72 hours after the onset of symptoms will be included. Studies with participants with a diagnosis other than STEMI or patients with STEMI of >12 hours complicated by heart failure, cardiogenic shock or ventricular arrhythmias, and studies of combined interventions (pharmacoinvasive strategy) were excluded. Two independent authors will identify the relevant publications, and discrepancies will be adjudicated by a third author. Data extraction will be performed by two independent authors and verified by a third author. Risk of bias of studies will be assessed using the Cochrane 'risk of bias' tool (RoB 2) or Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool. If appropriate, a meta-analysis will be performed in order to examine the effect of late revascularisation in clinical outcomes of interest.
ETHICS AND DISCUSSION
This study will use published data only, thus, ethical approval will not be required. The results will be disseminated through peer-reviewed publication and conference presentations.
PROSPERO REGISTRATION NUMBER
CRD42021283429.
Topics: Adult; Heart Failure; Humans; Meta-Analysis as Topic; Myocardial Reperfusion; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Systematic Reviews as Topic
PubMed: 36104139
DOI: 10.1136/bmjopen-2021-059610 -
Journal of the American Heart... Jan 2023Scavenger receptors (SRs) are a structurally heterogeneous superfamily of evolutionarily conserved receptors that are divided into classes A to J. SRs can recognize... (Review)
Review
Scavenger receptors (SRs) are a structurally heterogeneous superfamily of evolutionarily conserved receptors that are divided into classes A to J. SRs can recognize multiple ligands, such as modified lipoproteins, damage-associated molecular patterns, and pathogen-associated molecular patterns, and regulate lipid metabolism, immunity, and homeostasis. According to the literature, SRs may play a critical role in myocardial infarction and ischemia/reperfusion injury, and the soluble types of SRs may be a series of promising biomarkers for the diagnosis and prognosis of patients with acute coronary syndrome or acute myocardial infarction. In this review, we briefly summarize the structure and function of SRs and discuss the association between each SR and ischemic cardiac injury in patients and animal models in detail. A better understanding of the effect of SRs on ischemic cardiac injury will inspire novel ideas for therapeutic drug discovery and disease evaluation in patients with myocardial infarction.
Topics: Animals; Myocardial Infarction; Reperfusion Injury; Myocardial Reperfusion; Biomarkers; Receptors, Scavenger
PubMed: 36645089
DOI: 10.1161/JAHA.122.027862 -
American Journal of Physiology. Cell... Nov 2020Monocytes are critical mediators of the inflammatory response following myocardial infarction (MI) and ischemia-reperfusion injury. They are involved in both initiation... (Review)
Review
Monocytes are critical mediators of the inflammatory response following myocardial infarction (MI) and ischemia-reperfusion injury. They are involved in both initiation and resolution of inflammation and play an integral role in cardiac repair. The antagonistic nature of their function is dependent on their subset heterogeneity and biphasic response following injury. New advancements in single-cell transcriptomics and mass cytometry have allowed us to identify smaller, transcriptionally distinct clusters that may have functional relevance in disease and homeostasis. Additionally, recent insights into the spatiotemporal dynamics of monocytes following ischemic injury and their subsequent interactions with the endothelium and other immune cells reveal a complex interplay between monocytes and the cardiac milieu. In this review, we highlight recent findings on monocyte functional heterogeneity, present new mechanistic insight into monocyte recruitment and fate specification following MI, and discuss promising therapeutic avenues targeting monocytes for the treatment of ischemic heart disease.
Topics: Animals; Cell Lineage; Chemokines; Disease Models, Animal; Exosomes; Gene Expression Regulation; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukins; Isoflavones; Mice; Monocytes; Myocardial Infarction; Myocardial Reperfusion Injury; Receptors, Chemokine; Recovery of Function; Transcriptome
PubMed: 32877204
DOI: 10.1152/ajpcell.00330.2020