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Biomedical subjects

V Fuster

Publications and source records attributed to V Fuster.

At least 199 records · Page 11Linked to original sources
PubMed1995

A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesion progression. The initial (type 1) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

Aneurysm↗
PubMed1995

The three mechanisms for coronary artery disease progression: insights into future management.

The basic mechanisms of atherosclerotic progression have been well elucidated during the last few years. Basic experimental and clinical information has helped define the three stages of progression. In this review we outline the pathologic and clinical differences between slow, rapid, and intermediate progression. The eight morphologically different lesions (types I, II, III, IV, Va, Vb, Vc, and VI) in their various stages are defined. The relationship between specific type of lesion and chronic endothelial injury, cardiac risk factors, and increased vascular permeability to lipids is noteworthy. In regard to the acute coronary syndromes, the fate of plaque rupture and our understanding of "passive" vs. "active" rupture are defined. In addition to the phenomenon of plaque rupture, the thrombogenicity of atherosclerotic plaques in the genesis of coronary syndromes is described. The combination of plaque disruption and a high thrombogenic risk profile--including local and systemic factors--is vital to understanding the genesis of the acute coronary syndromes. In approaching the use of these new insights to arrest or reverse the atherosclerotic process, it is essential to remember that the disease process starts early in life and takes many years to progress to the symptomatic stage. The future holds promise for the development of preventive strategies to halt the progression of coronary disease--the number one killer in the United States.

Acute Disease↗
PubMed1995

T2-weighted contrast for NMR characterization of human atherosclerosis.

We sought to determine whether 1H NMR images without chemical-shift selection can adequately characterize the components of human atheromatous arteries. NMR, as a nondestructive, biochemical imaging tool, has the potential to identify lipids in atherosclerotic plaques but has not yet produced detailed images of atheroma components. Using 1H NMR spectroscopy at 9.4 T, we examined microdissected components of diseased and normal arteries to determine water relaxation constants (T1 and T2) as well as the relative content of mobile lipid. Relaxation times were also measured at 1.5 and 4.7 T. Sections of arteries with atherosclerotic lesions of graded severity were imaged at 1.5 and 9.4 T. The contrast-to-noise ratio (CNR) was used to assess lesion conspicuity. In the atheromatous core, the water NMR signal predominates over that of lipid (lipid-to-water ratio, 0.11). At 9.4 T, T2 is 20.2 ms for the atheromatous core, 30.1 ms for the collagenous cap, and 29.5 ms for normal media. This results in a high CNR on T2-weighted (T2w) images for atheromatous core compared with the collagenous cap and normal media. A similar contrast was measured at lower field strength. Calcifications do not generate appreciable signal due to their low water content but can be detected on T1-weighted (T1w) images. The water T2 contrast allows discrimination of the atheromatous lipid core from collagenous regions. The combination of T1w and T2w sequences permits in vitro identification of the atheromatous core, collagenous cap, calcifications, media, adventitia, and perivascular fat. The discrimination of collagen fibers that overlie lipid deposits permits study of plaque protection and stability at all field strengths and may provide the basis for in vivo microscopy of human atherosclerosis.

Adult↗
PubMed1995

Cell biology of restenosis post-angioplasty.

PTCA is a well established intervention to reduce the severity of atherosclerotic coronary stenosis. In spite of a primary success rate of 90 - 95%, late restenosis occurs in 30 - 50% of patients within 3/6 months of the procedure. Angioplasty in swine induces similar events to those found in humans, thus providing a model for studying strategies for intervention. Blood interaction to the damaged vessel wall occurs with reperfusion after the intervention. Therefore, the in vivo characterization of the interaction of cellular elements (platelets and white cells) and blood proteins with the exposed vascular cells in the vessel wall post-angioplasty may be necessary to identify early triggers of restenosis. Angioplasty was performed simultaneously in the coronary and carotid arteries of swine by fluoroscopy assisted standard techniques. Angiography was performed acutely post-dilatation and residual lumen diameter evaluated. Dilated vessels from 30 min to 6 h postintervention were processed to prepare RNA and preserved to perform immunohistochemistry. Dilatation injury induces maximal expression of c-fos 30 min and c-myc from 2 to 4 h postdilatation. Platelet deposition is initiated immediately post-dilatation as well as infiltration of fluid phase proteins on the damaged areas.

Angioplasty, Balloon, Coronary↗
PubMed1994

Acute biological response to laser balloon angioplasty in the atherosclerotic rabbit.

Laser balloon angioplasty with Nd:YAG energy has been proposed as a method to seal intimal dissection and prevent elastic recoil after balloon angioplasty. To better define the vessel response to laser balloon angioplasty, its effects on luminal diameter, Indium-111 labelled platelet deposition, and histology were studied in 10 atherosclerotic rabbits. Balloon angioplasty was performed in both iliac arteries and was followed by laser balloon angioplasty in only one iliac artery. The nonlased artery served as a control. Single (15-35 W for 20 sec) or repetitive laser pulses (12-25 W for 20 sec x 3) were used. Platelet deposition was quantified 2 hr after the intervention. Lumen diameter (mm) increased following balloon angioplasty from 0.99 +/- 0.47 (mean +/- SD) to 1.92 +/- 0.43 and 0.89 +/- 0.46 to 1.99 +/- 0.57 in the balloon and laser-treated arteries, respectively (P < 0.001 for both groups for comparisons to baseline, P = NS for between groups comparison). Laser balloon angioplasty resulted in a further increase in luminal diameter to 2.42 +/- 0.53 (P < 0.02) when compared to the post balloon angioplasty diameter. Platelet deposition (10(6)/cm vessel) was higher following laser balloon angioplasty (26.9, 10.2-189; median range) than after balloon angioplasty (10.6, 3.4-30), P < 0.001. Histologic evidence of laser "sealing" was present in only one artery. Thus although laser balloon angioplasty results in an improved lumen diameter, it is accompanied by increased platelet deposition. In the atherosclerotic rabbit model, abolition of vascular recoil rather than "sealing" seems to be the most important advantage of laser balloon angioplasty over conventional balloon angioplasty.

Angiography↗
PubMed1994

Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture.

OBJECTIVES: The purpose of this study was to determine whether different components of human atherosclerotic plaques exposed to flowing blood resulted in different degrees of thrombus formation. BACKGROUND: It is likely that the nature of the substrate exposed after spontaneous or angioplasty-induced plaque rupture is one factor determining whether an unstable plaque proceeds rapidly to an occlusive thrombus or persists as a nonocclusive mural thrombus. Although observational data show that plaque rupture is a potent stimulus for thrombosis, and exposed collagen is suggested to have a predominant role in thrombosis, the relative thrombogenicity of different components of human atherosclerotic plaques is not well established. METHODS: We investigated thrombus formation on foam cell-rich matrix (obtained from fatty streaks), collagen-rich matrix (from sclerotic plaques), collagen-poor matrix without cholesterol crystals (from fibrolipid plaques), atheromatous core with abundant cholesterol crystals (from atheromatous plaques) and segments of normal intima derived from human aortas at necropsy. Specimens were mounted in a tubular chamber placed within an ex vivo extracorporeal perfusion system and exposed to heparinized porcine blood (mean [+/- SEM] activated partial thromboplastin time ratio 1.5 +/- 0.04) for 5 min under high shear rate conditions (1,690 s-1). Thrombus was quantitated by measurement of indium-labeled platelets and morphometric analysis. Under similar conditions, substrates were perfused with heparinized human blood (2 IU/ml) in an in vitro system, and thrombus formation was similarly evaluated. RESULTS: Thrombus formation on atheromatous core was up to sixfold greater than that on other substrates, including collagen-rich matrix (p = 0.0001) in both heterologous and homologous systems. Although the atheromatous core had a more irregular exposed surface and thrombus formation tended to increase with increasing roughness, the atheromatous core remained the most thrombogenic substrate when the substrates were normalized by the degree of irregularity as defined by the roughness index (p = 0.002). CONCLUSIONS: The atheromatous core is the most thrombogenic component of human atherosclerotic plaques. Therefore, plaques with a large atheromatous core content are at high risk of leading to acute coronary syndromes after spontaneous or mechanically induced rupture because of the increased thrombogenicity of their content.

Animals↗
PubMed1994

Synergistic action of severe wall injury and shear forces on thrombus formation in arterial stenosis: definition of a thrombotic shear rate threshold.

OBJECTIVES: This study attempted to determine the influence of progressive degrees of stenosis on platelet deposition onto a severely damaged vessel wall. BACKGROUND: The severity of wall injury and increased shear forces have been proposed as the determinants of thrombus formation and growth in arterial stenosis. METHODS: Carotid angioplasty was performed in 15 mongrel dogs to produce severe wall damage. Group I (n = 9) had arteries with damage only. In group II (n = 14), progressive degrees of stenosis were produced at the center of the dilated area. Acute thrombus formation was evaluated by angiography at the time of angioplasty and platelet deposition/cm2 quantified by indium-111 labeling 1 h after the procedure. RESULTS: Severe wall damage (group I) produced a significant increase in platelet deposition compared with control arterial segments (8.19 +/- 3.82 vs. 3.62 +/- 2.52 platelets x 10(6)/cm2 [mean +/- SD], p < 0.05), and the presence of a stenosis (group II) further increased platelet deposition (36.98 +/- 3.82 platelets x 10(6)/cm2, p < 0.05). Angiographic filling defects or total occlusion was found in seven of the arteries in group II but in none in group I (p < 0.05). A shear rate of approximately 5,000 s-1, corresponding to a critical stenosis of 70% and a 1.5- to 1.6-mm diameter, was found to identify the arteries in which thrombosis was likely to occur (p < 0.05). Four of 5 arteries < 1.5 to 1.6 mm in diameter had angiographic filling defects or occlusion compared with 1 of 13 with less severe stenosis (p < 0.01). CONCLUSIONS: In low shear rate conditions, deep arterial injury will lead to mural thrombosis without further thrombus growth. When deep arterial injury occurs under critical local shear conditions, platelet deposition will be enhanced, and thrombosis may progress to total occlusion.

Angioplasty, Balloon↗
PubMed1994

Prospective evaluation of a prostacyclin-sparing aspirin formulation and heparin/warfarin in aspirin users with unstable angina or non-Q wave myocardial infarction at rest. The Antithrombotic Therapy in Acute Coronary Syndromes Research Group.

The aim of this trial was to compare the efficacy of combination antithrombotic therapy with a prostacyclin-sparing aspirin plus anticoagulation versus conventional aspirin plus anticoagulation, when added to antianginal therapy, in patients with unstable angina or non-Q wave myocardial infarction already being treated with aspirin. In a double-blind (for the aspirin) study, 144 prior aspirin users were randomized; 72 patients received controlled-release, prostacyclin-sparing aspirin 75 mg daily plus anticoagulation (intravenous heparin followed by warfarin to maintain the international normalized ratio at 2-3), and 72 patients received conventional aspirin 75 mg daily plus the same anticoagulation. Controlled-release aspirin was formulated to preserve endothelial cell prostacyclin synthesis. Trial therapy was begun by 13.2 +/- 12.3 h of qualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographic changes, myocardial infarction, or death, was analysed by intention to treat. At 12 weeks, events were: [table: see text] Twenty-six of the 42 (62%) recurrent ischaemic events occurred within 7 days of presentation. Four of the 144 patients (3%) experienced a major bleeding complication. It is concluded that in spite of maximal antithrombotic therapy, there is a significant failure rate of medical therapy in aspirin users presenting with unstable angina or non-Q wave myocardial infarction while at rest. Prostacyclin-sparing aspirin offers no clinical benefit over conventional aspirin.

Adult↗
PubMed1994

Antithrombotic therapy in coronary artery disease.

Antithrombotic therapy has assumed a central role in the therapy of the acute coronary syndromes and chronic coronary artery disease. The theoretical rationale for antithrombotic therapy, and the established and evolving roles of antiplatelet agents and anticoagulants in coronary disease are reviewed. Emphasis is focused on new antithrombotic agents and novel combinations of existing agents.

Angioplasty↗