Morphological predictors of restenosis after coronary stenting in humans.

Background: Experimental studies suggest that arterial injury and inflammation lead to increased neointimal growth after stenting. Despite the increased use of coronary stents in humans, there are only limited pathological data on the morphological features of in-stent restenosis.

Methods And Results: Detailed histology was performed on 116 stents, implanted > or =90 days in 87 coronary arteries, from 56 patients (mean age, 59+/-13 years).

Pathology of the unstable plaque.

The term "vulnerable" in the context of human coronary plaques was originally intended to provide a morphological description consistent with lesions prone to rupture. Coronary thrombosis is now recognized as a diverse process arising from plaque rupture, erosion, or calcified nodules. These findings have prompted the search for more definitive terminology to describe the precursor lesion of rupture, now referred to as "thin-cap fibroatheromas.

Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies.

Background: Elevations in serum C-reactive protein measured by high-sensitivity assay (hs-CRP) have been associated with unstable coronary syndromes. There have been no autopsy studies correlating hs-CRP to fatal coronary artery disease.

Methods And Results: Postmortem sera from 302 autopsies of men and women without inflammatory conditions other than atherosclerosis were assayed for hs-CRP.

Histopathologic alterations after endovascular radiation and antiproliferative stents: similarities and differences.

Background: Endovascular radiation and drug-eluting antiproliferative stents in experimental animals (normal pigs and rabbit arteries) show a decrease in the neointimal growth at 1 month vs. controls. However, this is accompanied by delayed healing characterized by persistence of neointimal fibrin (with or without inflammation), a decrease in smooth muscle cells, and incomplete endothelialization.

Early loss of thrombomodulin expression impairs vein graft thromboresistance: implications for vein graft failure.

Thrombosis is the major cause of early vein graft failure. Our aim was to determine whether alterations in the expression of the anticoagulant proteins, thrombomodulin (TM) and the endothelial cell protein C receptor (EPCR), impair endothelial thromboresistance that may contribute to vein graft failure. Immunohistochemical staining of autologous rabbit vein graft sections revealed that the expression of TM, but not EPCR, was reduced significantly early after graft implantation.

Morphological predictors of arterial remodeling in coronary atherosclerosis.

Background: Although arterial remodeling in atherosclerotic arteries affects luminal patency, the role of plaque components has not been systematically studied.

Methods And Results: Coronary segments (n=2885) were harvested from the hearts of 36 patients who died of severe coronary artery disease after perfusion fixation. Remodeling was determined by morphometric analysis of 657 sections selected as reference segments and 1318 segments with atheromatous plaques.

Apoptosis in atherosclerosis. Does it contribute to plaque instability?

Several reports have demonstrated apoptosis in the advanced human atheroma. Most clinical events however, are precipitated by plaque rupture, to a lesser extent erosion, and the development of occlusive thrombi. Whether the extent of apoptosis can influence lesion stability is not precisely known, however, there is emerging data supporting this role.

The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor lesion to acute coronary syndromes.

While the concept of plaque 'vulnerability' implies a propensity towards thrombosis, the term vulnerable was originally intended to provide a morphologic description consistent with plaques that are prone to rupture. It is now known that the etiology of coronary thrombi is diverse and can arise from entities of plaque erosion or calcified nodules. These findings have prompted the search for more definitive terminology to describe precursor lesions associated with rupture, now referred to as thin-cap fibroatheromas.

Pathology of Direct Myocardial Revascularization.

Since the last decade, there has been great interest in creating myocardial channels using energy sources and mechanical devices to enhance tissue perfusion as adjunctive therapy for refractory ischemic coronary artery disease. These studies are predicated on the fact that a portion of myocardium in the failing heart is in a state of hibernation. The creation of these channels may lead to neovascularization capable of reviving hibernating myocytes, thus improving cardiac function.

Pathophysiology of calcium deposition in coronary arteries.

BACKGROUND AND MORPHOLOGIC STUDIES: Because coronary artery calcification correlates highly with plaque burden, it is an excellent disease marker for atherosclerosis. However, it is not a sensitive indicator of disease activity, and does not predict luminal compromise because of compensatory remodeling. In addition, most data do not support the concept that plaque calcification is related to plaque instability.

Pathological analysis of local delivery of paclitaxel via a polymer-coated stent.

Background: Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored.

Methods And Results: Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel.

Intravascular sonotherapy decreases neointimal hyperplasia after stent implantation in swine.

Background: Intimal hyperplasia and subsequent in-stent restenosis remain a major limitation after stent implantation. In vitro cell culture studies show that low-frequency, noncavitational ultrasound energy may impact smooth muscle cell proliferation. Accordingly, we assessed the efficacy of intravascular sonotherapy treatment on intimal hyperplasia in a swine stent model.

Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression.

Background: Subclinical episodes of plaque disruption followed by healing are considered a mechanism of increased plaque burden. Detailed pathological studies of healed ruptures, however, are lacking.

Methods And Results: We identified acute and healed ruptures from 142 men who died of sudden coronary death and performed morphometric measurements of plaque burden, luminal stenosis, and smooth muscle cell phenotype.

Pathology of Transmyocardial Angiogenesis and Arteriogenesis.

Transmyocardial laser revascularization (TMLR) is increasingly used for improving myocardial perfusion in patients with diffuse coronary artery disease and refractory ischemia. The efficacy of TMLR, however, is in doubt because no definite increase in blood flow or longevity has been demonstrated. Although histologic results after TMLR show some neocapillary formation, the relative amount of angiogenesis is similar to what occurs naturally after myocardial infarction.

Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death.

Although apoptosis is a well-recognized phenomenon in chronic atherosclerotic disease, its role in sudden coronary death, in particular, acute plaque rupture is unknown. Culprit lesions from 40 cases of sudden coronary death were evaluated. Cases were divided into two mechanisms of death: ruptured plaques with acute thrombosis (n = 25) and stable plaques with and without healed myocardial infarction (n = 15).

Apoptosis and cardiomyopathy.

Apoptosis is a form of cell death that has been described as distinct from necrotic cell death. It is believed to be genetically programmed and occurs as a physiologic process in various organ systems of body. Although it has been tacitly believed that apoptosis does not occur in the terminally differentiated adult heart muscle cells, studies in endomyocardial biopsies from patients with dilated and ischemic cardiomyopathy and in explanted hearts from patients with end-stage heart failure undergoing cardiac transplantation have demonstrated histochemical evidence of apoptosis.

Burden of myocardial damage in cardiac allograft rejection: scintigraphic evidence of myocardial injury and histologic evidence of myocyte necrosis and apoptosis.

Background: Because myocardial damage determines morbidity and outcomes in heart transplant rejection, assessment of total burden of myocardial damage is highly desirable. In addition to myocyte necrosis, programmed cell death, or apoptosis, has recently been shown to contribute to cardiac allograft rejection. In the present study, we noninvasively determined myocardial damage by antimyosin scintigraphy and compared it with necrotic and apoptotic myocardial damage in endomyocardial biopsy (EMB) specimens.

Retrieval and analysis of particulate debris after saphenous vein graft intervention.

Objectives: This study was designed to evaluate the composition and quantity of particulate debris resulting from vein graft intervention.

Background: Distal embolization and "no reflow" are frequent and important complications resulting from angioplasty of diseased saphenous vein grafts. Little is known about the composition and quantity of embolic particulate debris associated with vein graft intervention, and no intervention has been shown to protect against its clinical consequences.

Cocaine-induced increase in the permeability function of human vascular endothelial cell monolayers.

The effects of cocaine on endothelial cell macromolecular transport, electrical resistance, and morphology were assessed. In confluent endothelial monolayers grown on microporus filters, cocaine (0.01 to 1 mmol/L) induced a rapid concentration-dependent increase in permeability to peroxidase and low density lipoprotein.

Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy.

Apoptosis has been shown to contribute to loss of cardiomyocytes in cardiomyopathy, progressive decline in left ventricular function, and congestive heart failure. Because the molecular mechanisms involved in apoptosis of cardiocytes are not completely understood, we studied the biochemical and ultrastructural characteristics of upstream regulators of apoptosis in hearts explanted from patients undergoing transplantation. Sixteen explanted hearts from patients undergoing heart transplantation were studied by electron microscopy or immunoblotting to detect release of mitochondrial cytochrome c and activation of caspase-3.

Histopathologic evaluation of an expanded polytetrafluoroethylene-nitinol stent endoprosthesis in canine iliofemoral arteries.

Purpose: The authors assess a new ePTFE-nitinol stent for its long-term patency, healing, and properties of endothelialization.

Materials And Methods: Adult greyhounds (n = 18) underwent bilateral iliofemoral placement of an endoprosthesis (Hemobahn) consisting of a nitinol stent lined with an ultrathin expanded polytetrafluoroethylene (ePTFE) material. Histologic and quantitative morphometric analyses were performed on devices explanted at 2 weeks and 1, 3, 6, and 12 months.