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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 -
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 -
Mediators of Inflammation 2017Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality. Reperfusion strategies are the current standard therapy for AMI. However, they may... (Review)
Review
Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality. Reperfusion strategies are the current standard therapy for AMI. However, they may result in paradoxical cardiomyocyte dysfunction, known as ischemic reperfusion injury (IRI). Different forms of IRI are recognized, of which only the first two are reversible: reperfusion-induced arrhythmias, myocardial stunning, microvascular obstruction, and lethal myocardial reperfusion injury. Sudden death is the most common pattern for ischemia-induced lethal ventricular arrhythmias during AMI. The exact mechanisms of IRI are not fully known. Molecular, cellular, and tissue alterations such as cell death, inflammation, neurohumoral activation, and oxidative stress are considered to be of paramount importance in IRI. However, comprehension of the exact pathophysiological mechanisms remains a challenge for clinicians. Furthermore, myocardial IRI is a critical issue also for forensic pathologists since sudden death may occur despite timely reperfusion following AMI, that is one of the most frequently litigated areas of cardiology practice. In this paper we explore the literature regarding the pathophysiology of myocardial IRI, focusing on the possible role of the calpain system, oxidative-nitrosative stress, and matrix metalloproteinases and aiming to foster knowledge of IRI pathophysiology also in terms of medicolegal understanding of sudden deaths following AMI.
Topics: Animals; Humans; Inflammation; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress
PubMed: 28286377
DOI: 10.1155/2017/7018393 -
International Journal of Clinical and... 2014Autophagy is an important constitutive intracellular catalytic process that occurs in basal conditions, as well as during stress in all tissues. It is induced during... (Review)
Review
Autophagy is an important constitutive intracellular catalytic process that occurs in basal conditions, as well as during stress in all tissues. It is induced during cellular growth, tissue differentiation and metabolic demands. The regulated expression is cytoprotective while its deregulation leads to varieties of diseases. It plays a vital role in ischemic heart disease, being beneficial and adaptive during ischemia while detrimental and lethal during reperfusion. Reperfusion injury is the consequence of this deregulated autophagy and the motive of its persistence during reperfusion is still obscure. A long standing debate persists as to the dual nature of autophagy and defining its clearer role in cell death as compared to the widely studied process, apoptosis. Despite the progresses in understanding of the process and identification of critical mediators, there is no therapeutic strategy to address its final outcome, the reperfusion injury. This lack of effective therapeutic strategies has even questioned the validity of the process as a single entity. We still continue to witness the devastation with standard cure of reperfusion. In this article, we review the process, highlight reperfusion injury and outline important studies being conducted for the prevention of reperfusion injury and offer cardio-protection.
Topics: Animals; Autophagy; Humans; Myocardial Infarction; Myocardial Reperfusion Injury
PubMed: 25674198
DOI: No ID Found -
Scientific Reports Apr 2023Malignant ventricular arrhythmias (VA) after acute myocardial infarction remain a major threat. Aim of this study was to characterize the electrophysiological and...
Malignant ventricular arrhythmias (VA) after acute myocardial infarction remain a major threat. Aim of this study was to characterize the electrophysiological and autonomic sequelae of cardiac ischemia and reperfusion (I/R) in mice during the first week post incident. Left ventricular function was serially assessed using transthoracic echocardiography. VA were quantified by telemetric electrocardiogram (ECG) recordings and electrophysiological studies on the 2nd and 7th day after I/R. Cardiac autonomic function was evaluated by heart rate variability (HRV) and heart rate turbulence (HRT). Infarct size was quantified by planimetric measures. I/R caused significant myocardial scarring and diminished left ventricular ejection fraction. The ECG intervals QRS, QT, QT, and JT were prolonged in I/R mice. Both spontaneous VA scored higher and the inducibility of VA was raised in I/R mice. An analysis of HRV and HRT indicated a relative reduction in parasympathetic activity and disturbed baroreflex sensitivity up to 7 days after I/R. In summary, during the first week after I/R, the murine heart reflects essential features of the human heart after myocardial infarction, including a greater vulnerability for VA and a decreased parasympathetic tone accompanied by decelerated depolarization and repolarization parameters.
Topics: Humans; Animals; Mice; Stroke Volume; Ventricular Function, Left; Myocardial Ischemia; Electrocardiography; Coronary Artery Disease; Myocardial Infarction; Arrhythmias, Cardiac; Myocardial Reperfusion; Heart Rate
PubMed: 37029160
DOI: 10.1038/s41598-023-32346-5 -
American Journal of Physiology. Heart... Jul 2019Cell death is an important component of the pathophysiology of any disease. Myocardial disease is no exception. Understanding how and why cells die, particularly in the... (Review)
Review
Cell death is an important component of the pathophysiology of any disease. Myocardial disease is no exception. Understanding how and why cells die, particularly in the heart where cardiomyocyte regeneration is limited at best, becomes a critical area of study. Ferroptosis is a recently described form of nonapoptotic cell death. It is an iron-mediated form of cell death that occurs because of accumulation of lipid peroxidation products. Reactive oxygen species and iron-mediated phospholipid peroxidation is a hallmark of ferroptosis. To date, ferroptosis has been shown to be involved in cell death associated with Alzheimer's disease, Huntington's disease, cancer, Parkinson's disease, and kidney degradation. Myocardial reperfusion injury is characterized by iron deposition as well as reactive oxygen species production. These conditions, therefore, favor the induction of ferroptosis. Currently there is no available treatment for reperfusion injury, which accounts for up to 50% of the final infarct size. This review will summarize the evidence that ferroptosis can induce cardiomyocyte death following reperfusion injury and the potential for this knowledge to open new therapeutic approaches for myocardial ischemia-reperfusion injury.
Topics: Animals; Ferroptosis; Humans; Iron; Lipid Peroxidation; Lipid Peroxides; Myocardial Reperfusion Injury; Myocytes, Cardiac; Oxidation-Reduction; Phospholipids; Signal Transduction
PubMed: 31050558
DOI: 10.1152/ajpheart.00076.2019 -
The Journal of Invasive Cardiology Nov 2014To correlate early and late mortality with markers of reperfusion in ST-elevation myocardial infarction (STEMI). (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To correlate early and late mortality with markers of reperfusion in ST-elevation myocardial infarction (STEMI).
BACKGROUND
Early reperfusion improves STEMI outcomes. Reperfusion can be assessed using angiographic (Thrombolysis in Myocardial Infarction [TIMI] flow grade or myocardial blush grade [MBG]) or electrocardiographic markers (ST-segment recovery (STR).
METHODS
We searched electronic databases for all STEMI randomized clinical studies from the last decade reporting markers of reperfusion and clinical outcome. We used a generalized estimating equation (GEE) model with logistic regression link in order to assess the correlation between each marker of reperfusion and mortality at 30 and 365 days. We also performed random effect meta-analysis for selected studies comparing mortality for specific categories of MBG.
RESULTS
We identified 44 studies with 19,955 patients. Final TIMI 3 flow was achieved in 87%, 70% had MBG 2 or 3, and 66% had complete STR. Average 30-day and 1-year mortality was 2.97 ± 2.34% and 4.11 ± 2.52%, respectively. Adjusting (study level) for age, diabetes, chronic kidney disease, infarct location, ejection fraction, and female sex, there was significant correlation between each of the three markers and 1-year mortality (P=.03 for TIMI 3; P=.02 for MBG 2 or 3; and P=.04 for STR). In nearly 6000 patients, there was substantial excess mortality in those with MBG 0/1 compared with MBG 2/3 (relative risk = 2.14 [1.65-2.77] with P<.001 at 30 days; relative risk = 1.49 [1.3-1.7] and P<.001 at 1 year).
CONCLUSION
After correcting for clinical factors known to affect outcome, there was a significant correlation between survival and better reperfusion.
Topics: Coronary Circulation; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Myocardial Reperfusion; Prognosis; Randomized Controlled Trials as Topic; Statistics as Topic; Stroke Volume; Survival Analysis; Thrombolytic Therapy
PubMed: 25364000
DOI: No ID Found -
Journal of the American Heart... Feb 2019See Editorial by Cenko et al.
See Editorial by Cenko et al.
Topics: Female; Heart; Humans; Male; Myocardial Infarction; Myocardial Reperfusion; Thrombolytic Therapy
PubMed: 30767600
DOI: 10.1161/JAHA.118.011835 -
Cardiovascular Revascularization... 2015Despite advances in primary percutaneous interventions (PPCI), management of microvascular obstructions in reperfused myocardial tissue remains challenging and is a... (Review)
Review
Despite advances in primary percutaneous interventions (PPCI), management of microvascular obstructions in reperfused myocardial tissue remains challenging and is a high-risk procedure. This has led to renewed interest in the coronary venous system as an alternative route of access to the myocardium. This article reviews historical data describing therapeutic options via cardiac veins as well as discussing the clinical potential and limitations of a catheter intervention: pressure controlled intermittent coronary sinus occlusion (PICSO). Collected experimental and clinical information suggest that PICSO also offers the potential for tissue regeneration beyond myocardial salvage. A meta-analysis of observer controlled pICSO application in animal studies showed a dose dependent reduction in infarct size of 29.3% (p < 0.001). Additionally, a 4-fold increase of hemeoxygenase-1 gene expression (p < 0.001) in the center of infarction and a 2.5 fold increase of vascular endothelial growth factor (VEGF) (p < 0.002) in border zones suggest that molecular pathways are initiating structural maintenance. Early clinical evidence confirmed significant salvage and event free survival in patients with acute myocardial infarction and risk reduction for event free survival 5 years after the acute event (p < 0.0001). This experimental and clinical evidence was recently corroborated using modern PICSO technology in PPCI showing a significant reduction of infarct size, when compared to matched controls (p < 0.04). PICSO enhances redistribution of flow towards deprived zones, clearing microvascular obstruction and leading to myocardial protection. Beyond salvage, augmentation of molecular regenerative networks suggests a second mechanism of PICSO involving the activation of vascular cells in cardiac veins, thus enhancing structural integrity and recovery.
Topics: Acute Coronary Syndrome; Animals; Blood Pressure; Cardiac Catheterization; Coronary Circulation; Coronary Sinus; Humans; Microcirculation; Myocardial Reperfusion Injury; Myocardium; Percutaneous Coronary Intervention; Regeneration; Regenerative Medicine; Tissue Survival; Treatment Outcome
PubMed: 25616738
DOI: 10.1016/j.carrev.2014.12.004