The no-reflow phenomenon: A basic mechanism of myocardial ischemia and reperfusion

Both animal models of experimental myocardial infarction and clinical studies on reperfusion therapy for acute myocardial infarction have provided evidence of impaired tissue perfusion at the microvascular level after initiation of reperfusion despite adequate restoration of epicardial vessel patency. Characteristics of this “no-reflow” phenomenon found in basic science investigations, such as distinct perfusion defects, progressive decrease of resting myocardial flow with ongoing reperfusion and functional vascular alterations are paralleled by clinical observations demonstrating similar features during the course of reperfusion. In experimental animal investigations of coronary occlusion and reperfusion, this no-reflow phenomenon could be characterized as a fundamental mechanism of myocardial ischemia and reperfusion. Major determinants of the amount of no-reflow are the duration of occlusion, infarct size, but also the length of reperfusion, as rapid expansion of perfusion defects occurs during reperfusion. Moreover, no-reflow appears to persist over a period of at least four weeks, a period when major steps of infarct healing take place. The significant association of the degree of compromised tissue perfusion at four weeks and indices of infarct expansion, found in chronic animal models of reperfused myocardial infarction, might be the pathoanatomic correlate for the prognostic significance observed in the clinical setting.     

The central role of conventional 12-lead ECG for the assessment of microvascular obstruction after percutaneous myocardial revascularization

Guidelines report that the optimal treatment for ST-elevation myocardial infarction (STEMI) is a primary percutaneous coronary intervention (PPCI) when performed timely by trained operators. Yet, the reopening of the infarct-related artery (IRA) is not always followed by myocardial reperfusion. This phenomenon is most commonly called “no-reflow”, is caused by microvascular obstruction (MVO) and is associated to a worse outcome. Electrocardiogram (ECG) is crucial for the diagnosis of STEMI, but is also useful for the assessment of MVO. In this review we summarize ECG-derived parameters associated to MVO and their prognostic relevance.     

急性心肌梗死的治疗进展--从再通到再灌注

对于急性心肌梗死患者冠状动脉的再灌注治疗已得到广泛开展。然而,由于微循环无复流现象的存在,使得梗死相关血管的再通并不完全意味着心肌水平再灌注的实现。几项研究发现,超过 25%的急性心肌梗死患者经成功的溶栓或经皮冠脉介入术后都存在无复流现象,即未达到充分的心肌再灌注。所以,我们应把更多的注意力和研究重点转移到对心肌微循环再灌注的实现,而非冠状动脉的再通。     

Thrombolytic treatment in acute myocardial infarction: neutrophil activation, peripheral leucocyte responses, and myocardial injury.

OBJECTIVE--To examine early leucocyte responses and neutrophil activation in acute myocardial infarction treated by streptokinase and to relate the findings to coronary recanalisation and indices of myocardial damage in order to provide further information about the role of neutrophils in the evolution of injury. DESIGN--Group analysis of paired blood samples, obtained before streptokinase treatment and one hour after it, and of three indirect measures of myocardial injury: left ventricular ejection fraction, QRS score, and peak creatine kinase. SETTING--The coronary care unit of a district general hospital. PATIENTS--39 patients with acute myocardial infarction who underwent paired blood sampling (before streptokinase and one hour after streptokinase) and cardiac catheterisation 5 (3-8) days later. END POINTS--Changes in peripheral white cell and neutrophil counts and plasma elastase one hour after streptokinase infusion. Comparison of these variables in patients with and without patency of the infarct related coronary artery. Correlations between these variables and indirect measures of myocardial injury. RESULTS--Neutrophil activation, as reflected by plasma elastase, increased sharply one hour after streptokinase. Total white cell and neutrophil counts also increased. Changes tended to be more pronounced in patients with patency of the infarct related artery, though the trend was not statistically significant. Neutrophil activation before streptokinase was unrelated to indirect indices of myocardial injury but only one hour after streptokinase a weak negative correlation with left ventricular ejection fraction had developed. Peripheral neutrophil responses showed a similar relation to ejection fraction and also correlated with peak creatine kinase and QRS score. CONCLUSIONS--Thrombolytic treatment in acute myocardial infarction is associated with an abrupt reactive neutrophil response which provides an early measure of injury. It is also associated with neutrophil activation, probably in response to coronary recanalisation and myocardial reperfusion. Activated neutrophils are recognised as mediators of reperfusion injury in experimental infarction and the data in the present study provide preliminary evidence of a similar pathogenic role in the clinical setting.     

Thrombolytic treatment in acute myocardial infarction: neutrophil activation, peripheral leucocyte responses, and myocardial injury.

OBJECTIVE--To examine early leucocyte responses and neutrophil activation in acute myocardial infarction treated by streptokinase and to relate the findings to coronary recanalisation and indices of myocardial damage in order to provide further information about the role of neutrophils in the evolution of injury. DESIGN--Group analysis of paired blood samples, obtained before streptokinase treatment and one hour after it, and of three indirect measures of myocardial injury: left ventricular ejection fraction, QRS score, and peak creatine kinase. SETTING--The coronary care unit of a district general hospital. PATIENTS--39 patients with acute myocardial infarction who underwent paired blood sampling (before streptokinase and one hour after streptokinase) and cardiac catheterisation 5 (3-8) days later. END POINTS--Changes in peripheral white cell and neutrophil counts and plasma elastase one hour after streptokinase infusion. Comparison of these variables in patients with and without patency of the infarct related coronary artery. Correlations between these variables and indirect measures of myocardial injury. RESULTS--Neutrophil activation, as reflected by plasma elastase, increased sharply one hour after streptokinase. Total white cell and neutrophil counts also increased. Changes tended to be more pronounced in patients with patency of the infarct related artery, though the trend was not statistically significant. Neutrophil activation before streptokinase was unrelated to indirect indices of myocardial injury but only one hour after streptokinase a weak negative correlation with left ventricular ejection fraction had developed. Peripheral neutrophil responses showed a similar relation to ejection fraction and also correlated with peak creatine kinase and QRS score. CONCLUSIONS--Thrombolytic treatment in acute myocardial infarction is associated with an abrupt reactive neutrophil response which provides an early measure of injury. It is also associated with neutrophil activation, probably in response to coronary recanalisation and myocardial reperfusion. Activated neutrophils are recognised as mediators of reperfusion injury in experimental infarction and the data in the present study provide preliminary evidence of a similar pathogenic role in the clinical setting.     

冠状动脉无复流现象的当前认识

经皮冠状动脉介入治疗（PCI）是急性ST段抬高性心肌梗死患者的首选治疗策略。虽然PCI后冠脉血流恢复，但仍经常观察到无复流现象，并且与较差的临床预后有关。导致该现象的病因机制复杂且相互关联，对这些机制的进一步认识有助于制定个性化的预防和治疗策略。可以使用冠脉造影、心肌对比超声及心脏磁共振等技术诊断无复流。许多药物可能改善实验室和临床无复流，但一些药物尚未明确地改善临床结果。     

Patency, Perfusion und Prognose beim akuten Herzinfarkt

Early restoration of bloodflow in the infarct-related coronary artery is the principal mechanism by which early reperfusion therapies may improve outcome in patients with acute myocardial infarction. The beneficial effect of reperfusion is independent of the therapy used (thrombolysis or PTCA), but, as shown in many studies, depends very much on the time to reperfusion. The achievement of a normal bloodflow in the infarct vessel, the so called TIMI 3 patency is considered to be the gold standard for the evaluation of the success of reperfusion therapy. However, there is increasing evidence from recent studies, that restoration of epicardial bloodflow does not necessarily indicate perfusion at the myocardial level. As unequivocally shown by contrast echocardiography using intracoronary injections of microbubbles, this is true even for TIMI Grade 3 flow, which correlates most strongly with prognosis and usually is associated with a very low mortality of about 3 to 4%. Angiographic patency not only is a sometimes unreliable indicator of myocardial reperfusion, but also involves an invasive procedure, is expensive and not universally available. A readily available and simple indicator of reperfusion is the early resolution of ST segment elevation. Complete ST resolution at 90 or 180 minutes after the initiation of treatment is associated with an excellent prognosis, even better than TIMI 3 patency. In contrast, no ST resolution indicates an in-hospital mortality which is about 8-fold greater than with complete ST resolution. Since ST resolution may be more closely related with the relief of ischemia than angiographic patency, the prognostic power of the combination of both indicators should be greater than that of either of them alone. Thus, it is evident from many studies that patency of the infarct-related artery is necessary for myocardial salvage in acute myocardial infarction, but it has to be achieved rapidly and has to be complete and sustained. However, even an early and perfect angiographic result achieved by thrombolysis or PTCA, does not consistently indicate myocardial reperfusion, and the mechanisms of the often called no-reflow phenomenon are still poorly understood. The possible contribution of reperfusion injury to poor clinical outcomes after adequate epicardial flow has been restored is also a matter of controversy and deserves further research. Promising results were derived from studies with GP IIb/IIIa inhibitors, in which improved microvascular flow and myocardial reperfusion were observed, when these agents were used as adjunct to thrombolysis and PTCA.     

Un infarctus du myocarde compliqué d’une rupture du pilier antérieur de la valve mitrale au cours d’une corticothérapie prolongée

The authors report anterolateral papillary muscle rupture, occurring in a 67-year-old patient admitted for acute coronary syndrome. Mitral regurgitation, a rare but dramatic complication of myocardial infarction, is most often a consequence of posterior papillary muscle rupture. The ‘protection’ of the anterior papillary muscle is associated with vascularization via a dual coronary artery supply. Possible myocardial weakening associated with long-term corticotherapy is otherwise discussed in this observation.     

Coronary flow reserve in acute myocardial infarction in a patient treated with primary venous angioplasty. Case report

Residual stenosis, dissection and/or microvascular damage have been proposed as mechanisms of impaired flow after primary angioplasty (PCI) for acute myocardial infarction (MI). In this report we present a patient who underwent PCI for acute anterior MI. Coronary flow reserve (CFR) assessment performed after balloon dilatation suggested possible improvement of coronary flow after stenting. However, we did not observe any improvement in CFR just after stent implantation. We conclude that in patients treated with primary PCI the use of additional pharmacological treatment to prevent microcirculation injury during reperfusion and slow-flow or no-reflow phenomenon should be considered.     

The late open artery hypothesis--a decade later

BACKGROUND: Early reperfusion after myocardial infarction has been proved to preserve left ventricular function and reduce mortality. However, a significant number of patients have persistent occlusion of the infarct-related artery late (days to weeks) after myocardial infarction because of ineligibility for thrombolytic therapy, failure of reperfusion, or reocclusion. METHODS: In this report we review the data on the potential mechanisms and benefits of late reperfusion and present prospective data on the incidence of and current practice patterns for the management of persistently occluded infarct-related arteries late after myocardial infarction. RESULTS: Although several studies have associated late patency of the infarct-related artery with improved long-term clinical outcome, they were nonrandomized and reflect selection bias. Furthermore, data on late patency from the largest study, Global Utilization of Steptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO-I), failed to confirm independent benefits of an open infarct-related artery 1 year after myocardial infarction. The randomized data on the effects of percutaneous transluminal coronary angioplasty for occluded infarct-related arteries late after myocardial infarction are limited and inconclusive. CONCLUSIONS: The hypothesis that late reperfusion by percutaneous coronary intervention days to weeks after myocardial infarction results in improved long-term clinical outcomes in asymptomatic patients with occluded infarct-related artery is currently being tested in the randomized, multicenter Occluded Artery Trial.     

Role of Adenosine as Adjunctive Therapy in Acute Myocardial Infarction

Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus “myocardial reperfusion injury” may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high‐risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil‐mediated microvascular injury resulting in a progressive decrease in blood flow (“no‐reflow” phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well‐characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardio‐protective effects of adenosine are supported by its role as a mediator of pre‐ and post‐conditioning. In experimental models, administration of adenosine in the peri‐reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct size and improves ventricular function. In the larger AMISTAD and AMISTAD II trials a 3‐h infusion of adenosine as an adjunct to reperfusion resulted in a striking reduction in infarct size (55–65%). Post hoc analysis of AMISTAD II showed that this was associated with significantly improved early and late mortality in patients treated within 3.17 h of symptoms. An intravenous infusion of adenosine for 3 h should be considered as adjunctive therapy in high risk‐patients undergoing reperfusion therapy.     

The neutrophil as a mediator of myocardial ischemia-reperfusion injury: time to move on

Granulocytes, especially neutrophils, are recruited in myocardium during the evolution of acute myocardial infarction. Because the neutrophil reaction is most intense during reperfusion and because these cells are a rich source of toxic oxidant species and proteolytic enzymes, it has become a widely held view that neutrophils are an important mechanism of myocardial injury extension during reperfusion. However, on close examination the evidence underlying this contention is equivocal. The basic experimental situation can be summarised thus. (1) All forms of reperfusion injury (i.e., cytotoxic or lethal cell injury, myocardial stunning, endothelial dysfunction, and reperfusion-induced arrhythmias) can be observed in neutrophil-free conditions. (2) “Anti-neutrophil” interventions (e.g., anti-inflammatory drugs, adenosine, anti-neutrophil antisera, leukocyte filters and inhibitors of the various pathways of neutrophil adhesion) do not consistently prevent reperfusion injury and they certainly do not consistently limit infarct size. (3) The time course of neutrophil accumulation in post-ischaemic myocardium may be different to the time course of injury. (4) Despite more than two decades of research, no double-blind, randomised controlled clinical trial assessing an anti-neutrophil therapy in myocardial infarction has yet reported a positive benefit that is attributable to inhibition of neutrophil recruitment. The evidence weighs against a pivotal role of neutrophils as a causal factor in most forms of ischemia-reperfusion injury. An exception may be microvascular injury and capillary plugging leading to the “no-reflow” phenomenon but even here the evidence suggests that the extent of neutrophil accumulation and microvascular injury is determined by, rather than a cause of, myocyte necrosis.     

Marked ST elevation after successful PTCA for acute myocardial infarction

Prompt reperfusion of acutely ischemic myocardium appears to be the rational way of reversing ischemic injury and limiting the extent of eventual necrosis. Recent advances in emergency coronary bypass surgery, percutaneous transluminal coronary angioplasty (PTCA) and thrombolytic therapy have provided methods for effective treatment of acute myocardial infarction. However, several observations indicate this issue is more complex. Although blood flow must be restored to ischemic myocardium if it is to survive, animal experiments suggest potential deleterious effects associated with this reperfusion. These deleterious effects may be associated with unstable ST segments reported early after acute infarct thrombolysis. Though recurrent coronary occlusion cannot be excluded, reperfusion injury in this setting of coronary artery patency must be considered. This case illustrates this proposed reperfusion injury reflected as "tombstone" ST segment elevation in a patient following successful acute infarct PTCA.     

Cardioprotection and pharmacological therapies in acute myocardial infarction: Challenges in the current era

In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification ofseveral promising pharmacological(cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proofof-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease.     

Early temporal changes in coronary flow velocity patterns in patients with acute myocardial infarction demonstrating the "no-reflow" phenomenon.

Coronary flow velocity pattern in patients with acute myocardial infarction demonstrating no-reflow phenomenon is characterized with early systolic retrograde flow and rapid deceleration of diastolic flow velocity. In this study, we investigated the early temporal changes in microvascular function in patients with the no-reflow phenomenon. Among 144 patients with a first acute myocardial infarction, 33 exhibited sizable no-reflow phenomenon after coronary reperfusion with myocardial contrast echocardiography. We assessed temporal changes in coronary flow velocity patterns with the Doppler guidewire. The early systolic retrograde flow was observed < or = 10 seconds after reperfusion in 16 patients (group A) or later in 17 patients (331 +/- 327 seconds, group B). Diastolic deceleration rate was higher in group A than in group B at 1 minute after reperfusion. It gradually increased in group B and showed comparable value to group A 10 minutes later. Group A had longer elapsed time from symptom onset to reperfusion and a greater number of infarct Q waves before reperfusion than group B (14 +/- 13 vs 5 +/- 2 hours, p <0.01; and 3 +/- 2 vs 2 +/- 1, p <0.02). In contrast, the incidence of transient ST reelevation shortly after reperfusion was higher in group B (76% vs 25%, p <0.01). Thus, the characteristic coronary flow velocity pattern is either established at the moment of coronary reperfusion or progresses thereafter in patients with no-reflow phenomenon. This suggests different mechanisms of developing ischemic microvascular injury.     

High Dose Bolus Heparin as Initial Therapy Before Primary Angioplasty for Acute Myocardial Infarction: Results of the Heparin in Early Patency (HEAP) Pilot Study

Objectives. We sought to determine the effect of high dose intravenous bolus heparin on early coronary patency before primary angioplasty.Background. Early coronary angiography after thrombolysis for acute myocardial infarction has shown better patency when intravenous heparin is used as an adjunct. The present study explores whether heparin alone can induce reperfusion.Methods. In the Heparin in Early Patency (HEAP) pilot study, 108 patients with signs and symptoms of acute myocardial infarction <6 h eligible for primary angioplasty received a single intravenous bolus of 300 U/kg of heparin together with aspirin (160 mg chewed) in the emergency room. The median dose of bolus heparin given was 27,000 U. Patency of the infarct-related artery (IRA) was assessed by coronary angiography at a median of 85 min after the heparin bolus.Results. In 55 patients (51%, 95% confidence interval 38% to 64%), Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 was observed at 90 min: TIMI flow grade 3 in 33 patients (31%); TIMI flow grade 2 in 22 (20%). Thirty-two (64%) of 50 patients with symptoms ≤2 h had TIMI flow grade 2 or 3 versus 23 (40%) of 58 patients with symptoms >2 h (p = 0.02). No significant bleeding was seen. Two patients (2%) died in the hospital. The patency results obtained in patients treated with the high dose bolus heparin were compared with those in 108 patients from a large primary angioplasty database, who were treated with standard therapy, including aspirin but not intravenous heparin, and were matched for clinical and angiographic characteristics with the HEAP pilot study patients. They showed an 18% patency rate (p < 0.001) of the IRA (TIMI flow grade 3 in 9%, TIMI flow grade 2 in 9%) before primary angioplasty.Conclusions. Early therapy with high dose heparin is associated with full coronary reperfusion in a considerable number of patients with acute myocardial infarction, especially in those treated early (<2 h). This simple, inexpensive, probably safe and easily antagonizable treatment may be an attractive first treatment of acute myocardial infarction both before and during the hospital stay in conjunction with primary angioplasty.     

Effect of intracoronary adenosine infusion during coronary intervention on myocardial reperfusion injury in patients with acute myocardial infarction

Despite early recanalization of an occluded infarct artery, up to 33% of patients with acute myocardial infarction do not obtain complete myocardial reperfusion due to a process of reperfusion injury. This study assessed whether adjunctive therapy with adenosine might prevent or attenuate the phenomenon of myocardial reperfusion injury. Myocardial reperfusion was assessed in 79 consecutive patients receiving a 20-minute intracoronary infusion of adenosine during percutaneous coronary intervention (PCI) and in a historical cohort of 200 patients with acute myocardial infarction who were treated with PCI (controls). Myocardial reperfusion injury was defined as persistent (> or =50% of initial value) ST-segment elevation after successful recanalization. Its effect on infarct size was evaluated by calculating the Selvester QRS score before intervention and at follow-up. Myocardial reperfusion injury was present in 19% of patients receiving adenosine versus 35% of control patients (p = 0.004). Evaluation of infarct expansion over time showed almost no change in the QRS score in patients receiving adenosine (3.4 +/- 3.0 before PCI; 3.5 +/- 3.1 at follow-up). In contrast, infarct QRS score in the control group worsened from 3.1 +/- 2.7 before PCI to 4.5 +/- 3.2 at follow-up (p = 0.003 treatment with adenosine vs control). Multivariate analysis identified adjunctive therapy with adenosine as an independent protective determinant of myocardial reperfusion injury and of infarct expansion. The rate of major adverse cardiac events (death and myocardial infarction) at 1 month tended to be lower in patients receiving adenosine (4% vs 6.5%, p = 0.7) and was mainly observed in patients with evidence of myocardial reperfusion injury (cardiac event rate 2% in patients with ST-segment elevation of <50% vs 14% in patients with ST-segment elevation > or =50%, p = 0.003). Thus, impaired myocardial reperfusion is the most important determinant of clinical outcome in patients with acute myocardial infarction treated with PCI. Adjunctive therapy with intracoronary infusion of adenosine during PCI prevents the occurrence of severe myocardial reperfusion injury and is associated with less infarct expansion.     

Post PCI atrial fibrillation

Atrial fibrillation (AF) is a major arrhythmia with a high prevalence among population. AF is not uncommon in the setting of coronary artery disease, including myocardial infarction (MI) and acute coronary syndromes (ACS). Percutaneous coronary interventions (PCI) have significantly improved outcomes of patients with acute MI and acute coronary syndromes. Nevertheless, the AF was reported to occur in patients with MI and ACS undergoing PCI. New onset AF after PCI for MI and ACS, though being infrequent, was associated with worse clinical course and prognosis. The predictive value of AF has tendency to change in parallel with improvements of reperfusion strategies and comprehensive treatment. Observational studies suggest better patency of culprit vessels achieved by PCI was accompanied by improvement in signal-averaged electrocardiography indices of atrial electrophysiological properties and higher rate of restoration of sinus rhythm during primary PCI as compared with thrombolysis. The adequate management of arrhythmia is required to reduce the risk of complications.     

Reperfusion in acute myocardial infarction: current concepts

Myocardial reperfusion is the treatment of choice in acute myocardial infarction. Pharmacological thrombolysis restores coronary artery patency in about two thirds of patients with acute myocardial infarction. However, mechanical reperfusion with primary angioplasty and stenting achieves higher patency rates with less complications, especially in high-risk patients. Adjunctive pharmacotherapy and new device technology may improve the outcome of primary angioplasty. Facilitated angioplasty using a combination of half-dose thrombolysis, platelet glycoprotein IIb/IIIa antagonists, and early intervention, appears to be a promising strategy for the treatment of acute myocardial infarction in the modern era. The efficacy and safety of this approach are currently evaluated in several ongoing trials. Copyright 2003, Elsevier Science (USA). All rights reserved.     

The open artery hypothesis: beneficial effects and long-term prognostic importance of patency of the infarct-related coronary artery

There seem to be additional mechanisms of benefit in patients receiving late reperfusion therapy in a time when the opportunity for myocardial salvage has been missed. Previous studies have demonstrated that the restoration of blood flow in the infarct-related coronary artery in patients with acute myocardial infarction improves left ventricular function and reduces mortality. Initially, it was thought that survival was improved because viable myocardium was salvaged. However, data obtained over the past several years have suggested that the restoration of antegrade flow in the infarct-related artery may improve survival via a mechanism independent of the influence on left ventricular function. Clinical interest in the open artery hypothesis has recently resurfaced owing to a substantial improvement in technical aspects of percutaneous coronary interventions (PCI). Observational data suggest a role for late intervention as safer and more effective mechanical reperfusion practices have emerged. Long-term clinical benefits have been shown from balloon angioplasty late after myocardial infarction (MI). Therefore, patients with failed thrombolysis or those with late-presenting MI may still benefit from PCI by mechanisms independent of myocardial salvage. There is accumulative evidence on this matter. Possible mechanisms include reduction of ventricular remodeling, diminished ventricular instability reducing the incidence of arrhythmias, and provision of collaterals to other territories in the event of further coronary artery occlusion. However, caution must be exercised in interpreting the results of studies examining the open artery hypothesis. This hypothesis can be tested in its purest sense in animal experiments; however, the clinical situation is much more complex. Patients may have acute-on-chronic coronary artery occlusion in the presence of multivessel disease and well-developed collateral channels. The pattern of necrosis may also be different with areas of necrosis separated by islands of ischemic, stunned, hibernating, or normal cells. Therefore, the patency of the infarct-related coronary artery in single or multivessel disease days to weeks after infarction markedly influences long-term prognosis unrelated to improvement of left ventricular function. Current technology has made it feasible to open and maintain patency of most occluded infarct-related arteries. However, the hypothesis that late mechanical reperfusion in patients with asymptomatic occluded infarct-related artery will improve long-term clinical outcomes remains to be proved and is currently being tested in a large randomized trial.