Pathophysiology of myocardial ischemia: Importance of platelet-vessel wall interactions

Parratt, J. R.

doi:10.1007/bf00054250

Cited by 5 publications

(1 citation statement)

References 37 publications

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“…There is growing evidence that also supports a role for platelets during the pathogenesis of reperfusion injury. Activated platelets are a source of various inflammatory mediators including arachidonic acid products, neutrophil activating peptide, and oxygen radicals [10][11][12]. Platelets express several adhesion molecules that mediate platelet adhesion to subendothelial matrix proteins [10,13].…”

Section: Introductionmentioning

confidence: 99%

Microvascular Aspects of Ischemia-Reperfusion Injury

Granger

Organ Microcirculation

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Summary. Ischemia-reperfusion (I/R) has been implicated in the pathogenesis of a number of diseases that affect a variety of organ systems. Research on this problem has led to the recognition that the microcirculation is particularly vulnerable to the deleterious effects of I/R. The microvascular dysfunction caused by I/R is manifested as impaired endothelium-dependent dilation in arterioles, enhanced fluid filtration and leukocyte plugging in capillaries, and the trafficking of leukocytes and platelets, as well as extravasation of plasma proteins in postcapillary venules. Activated endothelial cells in all segments of the microcirculation produce more oxygen radicals, and the bioavailability of nitric oxide diminishes after reperfusion. The resulting imbalance between superoxide and nitric oxide in endothelial cells leads to the production and release of inflammatory mediators and an enhanced biosynthesis of and increased cell surface expression of adhesion molecules that mediate the recruitment of both leukocytes and platelets. More recent evidence indicates that I/R reveals a link between inflammation and hemostasis, such that the accumulation of leukocytes coincides with the recruitment of platelets. Our work on intestinal venules indicates that approximately 40% of the adherent leukocytes are platelet bearing, and that platelets utilize P-selection to bind to the P-selectin glycoprotein ligand-1 that is constitutively expressed on the surface of leukocytes. A fraction of the platelets that accumulate in postischemic venules bind directly to activated endothelial cells. Some of the known risk factors for cardiovascular disease, including hypercholesterolemia, hypertension, and diabetes appear to exaggerate many of the microvascular alterations elicited by I/R. Finally, the inflammatory mediators released as a consequence of reperfusion also appear to activate endothelial 181 Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA cells in remote organs that are not directly exposed to the initial ischemic insult. This distant response to I/R can result in leukocyte-dependent microvascular injury that is characteristic of the multiple organ dysfunction syndrome.

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Section: Introductionmentioning

confidence: 99%

Microvascular Aspects of Ischemia-Reperfusion Injury

Granger

Organ Microcirculation

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Nitric Oxide, Platelet Function, Myocardial Infarction and Reperfusion Therapies

Alonso¹,

Radomski²

The Role of Nitric Oxide in Heart Failure

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Abstract. Platelets play an important role in physiologic hemostasis and pathologic thrombosis that complicate the course of vascular disorders. A number of platelet functions including adhesion, aggregation and recruitment are controlled by nitric oxide (NO) generated by platelets and the endothelial cells. Derangements in this generation may contribute to the pathogenesis of thrombotic complications of vascular disorders. The pharmacologic supplementation of the diseased vasculature with drugs releasing NO may help to restore the hemostatic balance.Key Words. nitric oxide, platelet function, myocardial infarction, reperfusion stimulate or inhibit the process of platelet activation. While thromboxane adenosine diphosphate and matrix metalloproteinase-2 mediate the activator platelet reactions [2], prostacyclin, ADPase and NO provide the platelet inhibitor pathways of regulation [3]. These labile mediators control the platelet surface abundance of major platelet receptors including P-selectin, glycoprotein (GP) Ib and GP IIb/IIIa [4][5][6]. The activation of these receptors leads to platelet adhesion to the components of the extracellular matrix and aggregation.Catastrophic events leading to myocardial ischemia and infarction result from atherosclerotic plaque rupture and are mediated to large extent by formation of occlusive platelet thrombus at the site of injury [1]. The objective of this article is to review the actions of nitric oxide (NO) in regulation of platelet function in physiology and during the coronary artery disease. We will also attempt to review the pharmacological effects of NO donors on the diseased coronary circulation.Blood platelets play a vital role in vascular hemostasis. Following an accidental injury, platelets adhere to the damaged portions of the vessel wall and then aggregate forming the hemostatic plug in order to seal the vessel and contain blood loss. This ability of the vasculature must be carefully balanced against the necessity to maintain the fluid state of blood in order to provide oxygen and nutrients to the cells and tissues. A failure to maintain blood in its fluid state leads to thrombosis, one of serious manifestations of vascular dysfunction. In order to maintain tight control over the process of platelet activation, regulatory mechanisms operate as an interactive system of agents that Nitric oxide (NO) is a gaseous biological mediator first identified as the endothelium-derived relaxing factor (EDRF) [7][8][9]. It is generated from the guanidino-nitrogen of L-arginine yielding citrulline (for review see [10]) and plays a prominent role in controlling a variety of functions in the cardiovascular, immune, reproductive, and nervous systems [11][12][13]. The production of NO is catalyzed by three major isoforms of the enzyme NO synthase (NOS): neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) [14][15][16]. The nNOS and eNOS are constitutively expressed and activated by calcium entry into cells [17,18], whereas iNOS is calcium-independent, and its synthesis is induce...

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