Microvascular dysfunction in acute myocardial infarction: focus on the roles of platelet and inflammatory mediators in the no-reflow phenomenon

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Abstract

Recent interest has shifted from infarct artery patency to microvascular perfusion in the evaluation of patients with acute myocardial infarction (AMI). Microvascular dysfunction occurs in a substantial proportion of patients, despite aggressive therapy with thrombolytic agents and/or percutaneous mechanical revascularization techniques. Patients with impaired microvascular perfusion after immediate reperfusion therapy have an adverse clinical prognosis. Recent studies have extended our understanding of the pathophysiology of this so-called no-reflow phenomenon, focusing on the critical roles of platelet and inflammatory mediators leading to microvascular obstruction and reperfusion injury. Moving beyond the Thrombolysis in Myocardial Infarction (TIMI) flow grade system, new techniques have been developed to assess microvascular perfusion, including TIMI frame counting, angiographic myocardial perfusion grading, myocardial contrast echocardiography, Doppler flow wire studies, nuclear scintigraphy, and magnetic resonance imaging. Armed with a greater understanding of the primary mediators of microvascular dysfunction, these tools may identify improved therapy directed at optimizing myocardial perfusion in patients with AMI.

Section snippets

Incidence of microvascular hypoperfusion after immediate reperfusion therapy

Acute ST-segment elevation myocardial infarction is typically caused by rupture of a coronary atherosclerotic plaque with subsequent thrombosis of an epicardial vessel. Immediate reperfusion therapy refers to fibrinolytic agents or mechanical transcatheter techniques that remove thrombus and open the IRA. “Reflow” is achieved when blood flow is restored beyond the site of the previous coronary occlusion.

The quality of coronary flow seen during coronary angiography has been quantified by the

Impact of microvascular dysfunction on clinical outcome

Numerous thrombolytic and angioplasty studies have demonstrated improvement in clinical outcome in patients with AMI who have early coronary reperfusion.

Pathophysiology of the no-reflow phenomenon

There are 2 potential explanations of TIMI 2 flow rates after immediate reperfusion therapy in patients with AMI. Residual thrombus, stenosis, or coronary dissection may give the appearance of a widely patent vessel and yet reduce coronary flow to the distal segment. Coronary angiography, however, can often identify these epicardial artery problems that may reduce coronary flow. In the current era of stenting, it is believed that residual luminal stenosis is not responsible for the development

Epidemiologic evidence: immune function in AMI patients

In addition to the vast body of experimental evidence suggesting a central role of neutrophil function in AMI patients, there is growing epidemiologic evidence supporting the role of the immune system in patients with ischemia and reperfusion injury.

Quantitative assessment of microvascular perfusion

Several diagnostic testing strategies have evolved that provide quantitative, objective assessment of microvascular flow.

Is no-reflow modifiable?

Management of myocardial hypoperfusion in AMI patients should be directed at the potential pathophysiologic mechanisms involved. Treating the phenomenon of platelet microembolism-related microvascular obstruction with aggressive antiplatelet therapy has yielded encouraging results. Therapeutic strategies addressing reperfusion injury appear promising in animal studies, but clinical trial data are still lacking.

The use of glycoprotein IIb/IIIa receptor inhibitors may improve microvascular

Conclusions

Despite optimal therapy with thrombolytic agents or primary angioplasty or stenting, a considerable number of patients are left with impaired epicardial coronary flow. An even greater proportion of patients has impaired microvascular perfusion, indicating a poorer prognosis with a higher adverse cardiac event rate. Current therapy is not successful in addressing the pathophysiology of microvascular dysfunction due to microvascular obstruction and reperfusion injury.

Looking beyond epicardial

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    Supported by Genentech, Inc., South San Francisco, California. Dr. Michaels also received support from the 1999–2000 American Heart Association Postdoctoral Fellowship Award.

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