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Journal of the American College of... Feb 1993Timely coronary reperfusion as treatment for acute myocardial infarction reduces myocardial infarct size, improves left ventricular function and survival. There is still... (Review)
Review
Timely coronary reperfusion as treatment for acute myocardial infarction reduces myocardial infarct size, improves left ventricular function and survival. There is still concern that at the time of reperfusion, a further injury occurs to the myocardium. Theoretically, if this "reperfusion injury" could be treated and eliminated, the outcome for patients with myocardial infarction might further improve. The concept of reperfusion injury is closely tied to the concept that oxygen radicals generated at the time of reperfusion cause tissue damage. There are four basic forms of reperfusion injury. Lethal reperfusion injury is described as myocyte cell death due to reperfusion itself rather than to the preceding ischemia. This concept continues to be controversial in both experimental animal and clinical studies. Vascular reperfusion injury refers to progressive damage to the vasculature over time during the phase of reperfusion. Manifestations of vascular reperfusion injury include an expanding zone of no reflow and a deterioration of coronary flow reserve. This form of reperfusion injury has been documented in animal models and probably occurs in humans. Stunned myocardium refers to postischemic ventricular dysfunction of viable myocytes and probably represents a form of "functional reperfusion injury." This phenomenon is well documented in both animal models and humans. Reperfusion arrhythmias represent the fourth form of reperfusion injury. They include ventricular tachycardia and fibrillation that occur within seconds to minutes of restoration of coronary flow after brief (5 to 15 min) episodes of myocardial ischemia. True reperfusion arrhythmias occur in only a small percentage of patients receiving thrombolytic therapy for acute myocardial infarction and are not a sensitive indicator for successful reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Arrhythmias, Cardiac; Cell Survival; Free Radicals; Humans; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Oxygen; Thrombolytic Therapy; Ventricular Function
PubMed: 8426022
DOI: 10.1016/0735-1097(93)90700-b -
Journal of Visualized Experiments : JoVE Jul 2012Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ischemia and...
Surgical trauma by thoracotomy in open-chest models of coronary ligation induces an immune response which modifies different mechanisms involved in ischemia and reperfusion. Immune response includes cytokine expression and release or secretion of endogenous ligands of innate immune receptors. Activation of innate immunity can potentially modulate infarct size. We have modified an existing murine closed-chest model using hanging weights which could be useful for studying myocardial pre- and postconditioning and the role of innate immunity in myocardial ischemia and reperfusion. This model allows animals to recover from surgical trauma before onset of myocardial ischemia. Volatile anesthetics have been intensely studied and their preconditioning effect for the ischemic heart is well known. However, this protective effect precludes its use in open chest models of coronary artery ligation. Thus, another advantage could be the use of the well controllable volatile anesthetics for instrumentation in a chronic closed-chest model, since their preconditioning effect lasts up to 72 hours. Chronic heart diseases with intermittent ischemia and multiple hit models are other possible applications of this model. For the chronic closed-chest model, intubated and ventilated mice undergo a lateral blunt thoracotomy via the 4th intercostal space. Following identification of the left anterior descending a ligature is passed underneath the vessel and both suture ends are threaded through an occluder. Then, both suture ends are passed through the chest wall, knotted to form a loop and left in the subcutaneous tissue. After chest closure and recovery for 5 days, mice are anesthetized again, chest skin is reopened and hanging weights are hooked up to the loop under ECG control. At the end of the ischemia/reperfusion protocol, hearts can be stained with TTC for infarct size assessment or undergo perfusion fixation to allow morphometric studies in addition to histology and immunohistochemistry.
Topics: Animals; Disease Models, Animal; Mice; Myocardial Ischemia; Myocardial Reperfusion
PubMed: 22847277
DOI: 10.3791/3896 -
Journal of General Internal Medicine Aug 2008Identify and describe interventions to reduce time to reperfusion for patients with ST-segment elevation myocardial infarction (STEMI). (Review)
Review
OBJECTIVE
Identify and describe interventions to reduce time to reperfusion for patients with ST-segment elevation myocardial infarction (STEMI).
DATA SOURCE
Key word searches of five research databases: MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Web of Science, and Cochrane Clinical Trials Registry.
INTERVENTIONS
We included controlled and uncontrolled studies of interventions to reduce time to reperfusion. One researcher reviewed abstracts and 2 reviewed full text articles. Articles were subsequently abstracted into structured data tables, which included study design, setting, intervention, and outcome variables. We inductively developed intervention categories from the articles. A second researcher reviewed data abstraction for accuracy.
MEASUREMENTS AND MAIN RESULTS
We identified 666 articles, 42 of which met inclusion criteria. We identified 11 intervention categories and classified them as either process specific (e.g., emergency department administration of thrombolytic therapy, activation of the catheterization laboratory by emergency department personnel) or system level (e.g., continuous quality improvement, critical pathways). A majority of studies (59%) were single-site pre/post design, and nearly half (47%) had sample sizes less than 100 patients. Thirty-two studies (76%) reported significantly lower door to reperfusion times associated with an intervention, 12 (29%) of which met or exceeded guideline recommended times. Relative decreases in times to reperfusion ranged from 15 to 82% for door to needle and 13-64% for door to balloon.
CONCLUSIONS
We identified an array of process and system-based quality improvement interventions associated with significant improvements in door to reperfusion time. However, weak study designs and inadequate information about implementation limit the usefulness of this literature.
Topics: Humans; Myocardial Infarction; Myocardial Reperfusion; Time Factors
PubMed: 18459014
DOI: 10.1007/s11606-008-0563-7 -
Emergency Medicine Journal : EMJ May 2006In this paper, we discuss and critically analyse pre-hospital management of acute myocardial infarction (AMI). It is clear from several large studies that rapid... (Review)
Review
In this paper, we discuss and critically analyse pre-hospital management of acute myocardial infarction (AMI). It is clear from several large studies that rapid diagnosis and application of thrombolysis reduces morbidity and mortality rates. Strategies that improve time to treatment in the pre-hospital setting are therefore of fundamental importance in the management of this fatal disease. The advantage of 12 lead electrocardiography use by paramedics to diagnose AMI and reduce time to treatment is discussed. Moreover, paramedic application of thrombolysis in the pre-hospital environment is examined. Several studies conducted worldwide support the notion that ambulance services can play a role in minimising time to treatment for patients with AMI. The contribution of early intervention by paramedics trained in critical care is potentially considerable, particularly in the important chain of survival that is often initiated by pre-hospital intervention.
Topics: Angioplasty, Balloon, Coronary; Early Diagnosis; Electrocardiography; Emergency Medical Services; Emergency Medical Technicians; Fibrinolytic Agents; Humans; Myocardial Infarction; Myocardial Reperfusion; Thrombolytic Therapy
PubMed: 16627830
DOI: 10.1136/emj.2005.028118 -
Circulation. Cardiovascular Quality and... Mar 2017Timely reperfusion is critical in acute ischemic stroke (AIS) and ST-segment-elevation myocardial infarction (STEMI). The degree to which hospital performance is...
BACKGROUND
Timely reperfusion is critical in acute ischemic stroke (AIS) and ST-segment-elevation myocardial infarction (STEMI). The degree to which hospital performance is correlated on emergent STEMI and AIS care is unknown. Primary objective of this study was to determine whether there was a positive correlation between hospital performance on door-to-balloon (D2B) time for STEMI and door-to-needle (DTN) time for AIS, with and without controlling for patient and hospital differences.
METHODS AND RESULTS
Prospective study of all hospitals in both Get With The Guidelines-Stroke and Get With The Guidelines-Coronary Artery Disease from 2006 to 2009 and treating ≥10 patients. We compared hospital-level DTN time and D2B time using Spearman rank correlation coefficients and hierarchical linear regression modeling. There were 43 hospitals with 1976 AIS and 59 823 STEMI patients. Hospitals' DTN times for AIS did not correlate with D2B times for STEMI (ρ=-0.09; =0.55). There was no correlation between hospitals' proportion of eligible patients treated within target time windows for AIS and STEMI (median DTN time <60 minutes: 21% [interquartile range, 11-30]; median D2B time <90 minutes: 68% [interquartile range, 62-79]; ρ=-0.14; =0.36). The lack of correlation between hospitals' DTN and D2B times persisted after risk adjustment. We also correlated hospitals' DTN time and D2B time data from 2013 to 2014 using Get With The Guidelines (DTN time) and Hospital Compare (D2B time). From 2013 to 2014, hospitals' DTN time performance in Get With The Guidelines was not correlated with D2B time performance in Hospital Compare (n=546 hospitals).
CONCLUSIONS
We found no correlation between hospitals' observed or risk-adjusted DTN and D2B times. Opportunities exist to improve hospitals' performance of time-critical care processes for AIS and STEMI in a coordinated approach.
Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Delivery of Health Care, Integrated; Female; Fibrinolytic Agents; Humans; Male; Middle Aged; Myocardial Reperfusion; Organizational Objectives; Patient Care Team; Prospective Studies; Quality Improvement; Quality Indicators, Health Care; Registries; ST Elevation Myocardial Infarction; Stroke; Thrombolytic Therapy; Time Factors; Time-to-Treatment; Tissue Plasminogen Activator; United States
PubMed: 28283469
DOI: 10.1161/CIRCOUTCOMES.116.003148 -
American Journal of Physiology.... Nov 2017Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial...
Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia-reperfusion (I/R) injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. We found that glucose uptake was remarkably diminished in the myocardium following reperfusion in Sprague-Dawley rats as detected by F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by threefold and GLUT4 translocation remained unchanged compared with those of sham-treated rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated I/R injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, whereas its knockdown increased glucose uptake, suggesting that PDK4 has a role in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial I/R. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in the myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial I/R injury.
Topics: Animals; Animals, Newborn; Carbohydrate Metabolism; Cells, Cultured; Glucose; Heart; Male; Myocardial Reperfusion; Myocardial Reperfusion Injury; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Recovery of Function
PubMed: 28325730
DOI: 10.1152/ajpendo.00014.2017 -
Journal of the American College of... Aug 2020
Topics: Heart Ventricles; Humans; Myocardial Infarction; Myocardial Reperfusion
PubMed: 32762904
DOI: 10.1016/j.jacc.2020.06.032 -
Journal of the American College of... Feb 2005The optimal reperfusion strategy in elderly patients with ST-segment elevation myocardial infarction (STEMI) remains a topic of debate. This lack of consensus stems from... (Review)
Review
The optimal reperfusion strategy in elderly patients with ST-segment elevation myocardial infarction (STEMI) remains a topic of debate. This lack of consensus stems from the exclusion or under-representation of the elderly in clinical trials. This review evaluates the available literature pertaining to reperfusion therapy for the treatment of STEMI in the elderly. We identified all published studies evaluating the effectiveness of thrombolytic therapy, primary percutaneous coronary intervention (PCI), or adjunctive therapies to reperfusion by conducting an electronic search of MEDLINE through December 2003. Meta-analysis of clinical trials suggests a survival benefit of thrombolytic therapy in the elderly with STEMI, whereas some observational studies have raised concerns about the lack of short-term benefit or possibility of harm with thrombolysis. However, most observational studies demonstrate improved intermediate-term survival with thrombolysis. In contrast, multiple clinical trials and observational studies indicate improved survival and low risk of stroke with primary PCI compared with thrombolysis in elderly patients with STEMI. Information on the efficacy of newer antithrombotic agents as adjunct to thrombolysis or primary PCI is scarce. Available data suggest an increased risk of intracerebral bleeding with the combination of a fibrin-specific agent and a glycoprotein IIb/IIIa receptor antagonist in patients >75 years of age. Clearly targeted large-scale clinical trials are needed to evaluate the relative merits of available reperfusion strategies as well as newer antithrombotic adjunctive therapies in the elderly with STEMI.
Topics: Aged; Angioplasty, Balloon, Coronary; Clinical Protocols; Combined Modality Therapy; Fibrinolytic Agents; Forecasting; Humans; Injections, Intravenous; Myocardial Infarction; Myocardial Reperfusion; Randomized Controlled Trials as Topic; Registries; Thrombolytic Therapy
PubMed: 15708688
DOI: 10.1016/j.jacc.2004.10.065 -
Circulation Journal : Official Journal... Jan 2017Tissue salvage of severely ischemic myocardium requires timely reperfusion by thrombolysis, angioplasty, or bypass. However, recovery of left ventricular function is... (Review)
Review
Tissue salvage of severely ischemic myocardium requires timely reperfusion by thrombolysis, angioplasty, or bypass. However, recovery of left ventricular function is rare. It may be absent or, even worse, reperfusion can induce further damage. Laboratory studies have shown convincingly that reperfusion can increase injury over and above that attributable to the pre-existing ischemia, precipitating arrhythmias, suppressing the recovery of contractile function ("stunning") and possibly even causing cell death in potentially salvable ischemic tissue. The mechanisms of reperfusion injury have been widely studied and, in the laboratory, it can be attenuated or prevented. Disappointingly, this is not the case in the clinic, particularly after thrombolysis or primary angioplasty. In contrast, excellent results have been achieved by surgeons by means of cardioplegia and hypothermia. For the interventionist, the issue is more complex as, contrary to cardiac surgery where the cardioplegia can be applied before ischemia and the heart can be stopped, during an angioplasty the heart still has to beat to support the circulation. We analyze in detail all these issues.
Topics: Animals; Humans; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Time Factors; Ventricular Function, Left
PubMed: 27941300
DOI: 10.1253/circj.CJ-16-1124 -
Nature Reviews. Cardiology Nov 2017Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain... (Review)
Review
Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse remodelling of the heart in the months that follow. Given that attempts to further reduce myocardial infarct size beyond early reperfusion in clinical trials have so far been disappointing, effective therapies are still needed to protect the reperfused myocardium. In this Review, we discuss several approaches to preserving the reperfused heart, such as therapies that target the mechanisms involved in mitochondrial bioenergetics, pyroptosis, and autophagy, as well as treatments that harness the cardioprotective properties of inhaled anaesthetic agents. We also discuss potential therapies focused on correcting the no-reflow phenomenon and its effect on healing and adverse left ventricular remodelling.
Topics: Coronary Circulation; Humans; Myocardial Reperfusion; No-Reflow Phenomenon; Postoperative Period; ST Elevation Myocardial Infarction; Ventricular Remodeling
PubMed: 28748958
DOI: 10.1038/nrcardio.2017.102