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Journal of the American College of... Apr 2015The damage inflicted on the myocardium during acute myocardial infarction is the result of 2 processes: ischemia and subsequent reperfusion (ischemia/reperfusion... (Review)
Review
The damage inflicted on the myocardium during acute myocardial infarction is the result of 2 processes: ischemia and subsequent reperfusion (ischemia/reperfusion injury). During the last 3 decades, therapies to reduce ischemic injury (mainly reperfusion strategies) have been widely incorporated into clinical practice. The remarkable reduction in death rates achieved with these therapies has resulted in a shift in emphasis from efforts to reduce mortality to a focus on tackling the downstream consequence of survival: post-infarction heart failure. Infarct size is the main determinant of long-term mortality and chronic heart failure, and thus, the possibility of limiting the extent of necrosis during an ST-segment elevation myocardial infarction is of great individual and socioeconomic value. After the great success of therapies to reduce ischemic injury, the time has come to focus efforts on therapies to reduce reperfusion injury, but in the recent few years, few interventions have successfully passed the proof-of-concept stage. In this review, we examine the past, present, and future therapies to reduce ischemia/reperfusion injury.
Topics: Animals; Glucagon-Like Peptide 1; Humans; Ischemic Preconditioning, Myocardial; Myocardial Reperfusion; Myocardial Reperfusion Injury; Randomized Controlled Trials as Topic
PubMed: 25857912
DOI: 10.1016/j.jacc.2015.02.032 -
Lancet (London, England) Jan 2017Acute myocardial infarction has traditionally been divided into ST elevation or non-ST elevation myocardial infarction; however, therapies are similar between the two,... (Review)
Review
Acute myocardial infarction has traditionally been divided into ST elevation or non-ST elevation myocardial infarction; however, therapies are similar between the two, and the overall management of acute myocardial infarction can be reviewed for simplicity. Acute myocardial infarction remains a leading cause of morbidity and mortality worldwide, despite substantial improvements in prognosis over the past decade. The progress is a result of several major trends, including improvements in risk stratification, more widespread use of an invasive strategy, implementation of care delivery systems prioritising immediate revascularisation through percutaneous coronary intervention (or fibrinolysis), advances in antiplatelet agents and anticoagulants, and greater use of secondary prevention strategies such as statins. This seminar discusses the important topics of the pathophysiology, epidemiological trends, and modern management of acute myocardial infarction, focusing on the recent advances in reperfusion strategies and pharmacological treatment approaches.
Topics: Anticoagulants; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Myocardial Reperfusion; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Assessment; Thrombolytic Therapy
PubMed: 27502078
DOI: 10.1016/S0140-6736(16)30677-8 -
European Heart Journal Mar 2017The incidence of ST segment elevation myocardial infarction (STEMI) has decreased over the last two decades in developed countries, but mortality from STEMI despite... (Review)
Review
The incidence of ST segment elevation myocardial infarction (STEMI) has decreased over the last two decades in developed countries, but mortality from STEMI despite widespread access to reperfusion therapy is still substantial as is the development of heart failure, particularly among an expanding older population. In developing countries, the incidence of STEMI is increasing and interventional reperfusion is often not available. We here review the pathophysiology of acute myocardial infarction and reperfusion, notably the temporal and spatial evolution of ischaemic and reperfusion injury, the different modes of cell death, and the resulting coronary microvascular dysfunction. We then go on to briefly characterize the cardioprotective phenomena of ischaemic preconditioning, ischaemic postconditioning, and remote ischaemic conditioning and their underlying signal transduction pathways. We discuss in detail the attempts to translate conditioning strategies and drug therapy into the clinical setting. Most attempts have failed so far to reduce infarct size and improve clinical outcomes in STEMI patients, and we discuss potential reasons for such failure. Currently, it appears that remote ischaemic conditioning and a few drugs (atrial natriuretic peptide, exenatide, metoprolol, and esmolol) reduce infarct size, but studies with clinical outcome as primary endpoint are still underway.
Topics: Animals; Cardiotonic Agents; Coronary Circulation; Disease Models, Animal; Humans; Ischemic Postconditioning; Ischemic Preconditioning, Myocardial; Microvascular Angina; Myocardial Reperfusion; Myocardial Reperfusion Injury; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Single Photon Emission Computed Tomography Computed Tomography; Treatment Outcome
PubMed: 27354052
DOI: 10.1093/eurheartj/ehw224 -
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 -
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 -
International Journal of Cardiology Aug 2011Despite being the most effective means of limiting infarct size, coronary reperfusion comes at a price and induces additional damage to the myocardium. Lethal... (Review)
Review
Despite being the most effective means of limiting infarct size, coronary reperfusion comes at a price and induces additional damage to the myocardium. Lethal reperfusion injury (death of myocytes that were viable at the time of reperfusion) is an increasingly acknowledged phenomenon. There are many interconnected mechanisms involved in this type of cell death. Calcium overload (generating myocyte hypercontracture), rapid recovery of physiological pH, neutrophil infiltration of the ischemic area, opening of the mitochondrial permeability-transition-pore (PTP), and apoptotic cell death are among the more important mechanisms involved in reperfusion injury. The activation of a group of proteins called reperfusion injury salvage kinases (RISK) pathway confers protection against reperfusion injury, mainly by inhibiting the opening of the mitochondrial PTP. Many interventions have been tested in human trials triggered by encouraging animal studies. In the present review we will explain in detail the main mechanism involved in reperfusion injury, as well as the various approaches (pre-clinical and human trials) performed targeting these mechanisms. Currently, no intervention has been consistently shown to reduce reperfusion injury in large randomized multicenter trials, but the research in this field is intense and the future is highly promising.
Topics: Animals; Humans; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury
PubMed: 21093938
DOI: 10.1016/j.ijcard.2010.10.056 -
American Heart Journal Nov 2015More than 20 years of misconceptions derailed acceptance of reperfusion therapy for acute myocardial infarction (AMI). Cardiologists abandoned reperfusion for AMI using... (Review)
Review
More than 20 years of misconceptions derailed acceptance of reperfusion therapy for acute myocardial infarction (AMI). Cardiologists abandoned reperfusion for AMI using fibrinolytic therapy, explored in 1958, because they no longer attributed myocardial infarction to coronary thrombosis. Emergent aortocoronary bypass surgery, pioneered in 1968, remained controversial because of the misconception that hemorrhage into reperfused myocardium would result in infarct extension. Attempts to limit infarct size by pharmacotherapy without reperfusion dominated research in the 1970s. Myocardial necrosis was assumed to progress slowly, in a lateral direction. At least 18 hours was believed to be available for myocardial salvage. Afterload reduction and improvement of the microcirculation, but not reperfusion, were thought to provide the benefit of streptokinase therapy. Finally, coronary vasospasm was hypothesized to be the central mechanism in the pathogenesis of AMI. These misconceptions unraveled in the late 1970s. Myocardial necrosis was shown to progress in a transmural direction, as a "wave front," beginning with the subendocardium. Reperfusion within 6 hours salvaged a subepicardial ischemic zone in experimental animals. Acute angiography provided in vivo evidence of the high incidence of total coronary occlusion in the first hours of AMI. In 1978, early reperfusion by transluminal recanalization was shown to be feasible. The pathogenetic role of coronary thrombosis was definitively established in 1979 by demonstrating that intracoronary streptokinase rapidly restored flow in occluded infarct-related arteries, in contrast to intracoronary nitroglycerine which rarely did. The modern reperfusion era had dawned.
Topics: Humans; Myocardial Infarction; Myocardial Reperfusion
PubMed: 26542507
DOI: 10.1016/j.ahj.2015.08.005 -
The American Journal of Cardiology Mar 1994Experimental studies have demonstrated that reperfusion is associated with a host of distinctive pathophysiologic derangements, the most important of which are... (Review)
Review
Experimental studies have demonstrated that reperfusion is associated with a host of distinctive pathophysiologic derangements, the most important of which are reperfusion arrhythmias, transient mechanical dysfunction or "myocardial stunning," and cell death. Reperfusion arrhythmias and myocardial stunning occur in experimental animals after transient ischemia followed by reperfusion, and there is considerable evidence that these derangements also develop in humans, although the existence of malignant reperfusion arrhythmias in humans remains uncertain. Reperfusion arrhythmias and myocardial stunning can be considered manifestations of sublethal, reversible cellular injury. The pathogenesis of reperfusion arrhythmias and stunning has not been conclusively established; however, there is considerable evidence that generation of oxygen radicals and perturbations of calcium homeostasis play an important role. Antioxidants and calcium antagonists have been shown to mitigate these manifestations of reperfusion injury. In contrast, the likelihood of lethal reperfusion-induced injury remains highly controversial. Although many studies have reported reduction of infarct size with antioxidants, numerous others have failed to reproduce these results. Consequently, intense controversy persists regarding whether oxygen radicals contribute to extending cell death following reperfusion and whether reperfusion itself causes cell death. Neither the resolution of this controversy nor the availability of clinical therapies to reduce reperfusion-induced cell death is likely in the near future.
Topics: Animals; Antioxidants; Arrhythmias, Cardiac; Cell Death; Free Radicals; Humans; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardial Stunning; Reactive Oxygen Species
PubMed: 8141076
DOI: 10.1016/0002-9149(94)90257-7 -
Drug and Therapeutics Bulletin Jul 2005Each year, around 240,000 people in England and Wales have an acute myocardial infarction. Of these, around half die within a month, many before reaching medical help.... (Review)
Review
Each year, around 240,000 people in England and Wales have an acute myocardial infarction. Of these, around half die within a month, many before reaching medical help. The likelihood of early and longer-term morbidity (e.g. heart failure, arrhythmias) and death is related to the extent of myocardial damage. Rapid restoration of blood flow to the affected muscle (reperfusion) limits the damage and improves the clinical outlook. Here we discuss different methods of achieving reperfusion in patients with myocardial infarction.
Topics: Angioplasty, Balloon, Coronary; Combined Modality Therapy; Humans; Myocardial Infarction; Myocardial Reperfusion; Thrombolytic Therapy
PubMed: 16035215
DOI: 10.1136/dtb.2005.43749 -
Journal of the American Heart... Oct 2014
Comparative Study Review
Topics: Angioplasty, Balloon, Coronary; Electrocardiography; Female; Heart Rupture, Post-Infarction; Humans; Male; Myocardial Infarction; Myocardial Reperfusion; Prognosis; Risk Assessment; Survival Analysis; Thrombolytic Therapy; Treatment Outcome
PubMed: 25332182
DOI: 10.1161/JAHA.114.001368