Cardiovascular & Hematological Disorders-Drug Targets

(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders)

Garry X. Shen  
University of Manitoba
Winnipeg, MB
Canada

Back

Microvascular Thrombosis: An Exciting but Elusive Therapeutic Target in Reperfused Acute Myocardial Infarction

Author(s): Jose A. Barrabes, Javier Inserte, Luis Agullo, Albert Alonso, Maribel Mirabet, David Garca-Dorado.

Abstract:

The beneficial effects of restoration of coronary flow in patients with acute myocardial infarction may be hampered by inadequate tissue perfusion. Among other factors, it is likely that platelets contribute substantially to this phenomenon. Platelets may compromise blood flow at the microvascular level by forming a part of microemboli, by adhering to reperfused, capillary or venular endothelium or to attached leukocytes, by releasing substances producing vasoconstriction, or through toxic effects. Patients with acute coronary syndromes have an increased number of circulating activated platelets, and this systemic platelet activation has been related to the presence and extent of myocardial necrosis. The mechanisms of platelet deposition to reperfused microvessels are not fully understood, but likely involve the interaction between adhesion molecules such as selectins or glycoproteins expressed on these cells upon activation and their ligands on the surface of endothelial cells or polymorphonuclear leukocytes. While these interactions are potentially important therapeutic targets in acute myocardial infarction, reducing platelet deposition and increasing myocardial salvage by direct effects on the microvasculature is still challenging with the existing armamentarium of antiplatelet agents. This review summarizes the current knowledge on the mechanisms of platelet-mediated myocardial damage after reperfusion and the effects of pharmacological interventions aimed to reduce microvascular platelet deposition and platelet-mediated myocardial injury.

Keywords: Platelets, reperfusion, microcirculation, ischemia, antithrombotic agents, acute myocardial infarction, microemboli, glycoproteins, polymorphonuclear leukocytes, thrombolytic treatment, epiphenomenon, necrosis, edema, creatinkinase-MB, troponin, thromboxane A2, arrhythmias, lactate dehydrogenase, coronary microembolization, microvasculature, glycoprotein IIb/IIIa, P-selectin, fibrinogen, serotonin, leukocytes, cardiomyocytes, thrombosis, aspirin, thrombolytic therapy, Thrombolysis, clopidogrel, abciximab, streptokinase, armamentarium

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 10
ISSUE: 4
Year: 2010
Page: [273 - 283]
Pages: 11
DOI: 10.2174/187152910793743797
Price: $58