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Biomedical subjects

V Fuster

Publications and source records attributed to V Fuster.

At least 253 records · Page 14Linked to original sources
PubMed1993

Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs.

BACKGROUND: Hypercholesterolemia is characterized by a coronary vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. This abnormality may be due to reduced synthesis of endothelium-derived relaxing factor and/or enhanced synthesis and release of an endothelium-derived contracting factor. Endothelin is an endothelium-derived vasoconstrictor and mitogenic peptide that is present in normal plasma, and its circulating concentrations are elevated in disease states that are characterized by abnormal endothelium-dependent relaxation to acetylcholine. The current studies were designed to test the hypotheses that experimental hypercholesterolemia results in elevation of plasma and tissue endothelin immunoreactivity and that the abnormal acetylcholine-evoked coronary vasoconstriction in the hypercholesterolemic animals is associated with further elevation of plasma endothelin. METHODS AND RESULTS: Plasma concentrations and molecular forms of endothelin immunoreactivity were determined following 2% cholesterol diet for 4 months in pigs and during intracoronary acetylcholine administration. Second, we assessed the presence of endothelin in the coronary vascular wall by using immunohistochemistry. Hypercholesterolemia elevated plasma endothelin concentration and enhanced coronary artery tissue endothelin immunoreactivity. The endothelium-dependent vasodilator acetylcholine further increases plasma endothelin in hypercholesterolemia in association with coronary vasoconstriction. The predominant molecular form of endothelin in hypercholesterolemia is the biological active endothelin-1. CONCLUSIONS: This study suggests a role for endothelin as an early participant and a marker for the endothelial dysfunction in hypercholesterolemia as well as a participant in the atherogenic process.

Acetylcholine↗
PubMed1993

Atherogenesis and inflammation.

Following endothelial injury, monocytes attach to the subendothelium and penetrate into the vessel wall, forming macrophage/foam cells by accumulating lipids. Macrophages release various products such as interleukins, complement factor fragments, tumour necrosis factors, oxidized cholesterol, and oxygen free radicals, leading to further endothelial injury and cytolysis. Platelets at the site of vascular injury, monocytes, endothelial cells, and smooth muscle cells release mitogenic factors which stimulate smooth muscle cell proliferation and migration. This smooth muscle cell proliferation, together with organization of thrombus and extracellular matrix synthesis, leads to the development of atheromatous plaques. Macrophages, by releasing proteases such as collagenase and elastase, form an abscess in the plaque which is covered by a thin fibrous cap. When this cap ruptures, a local thrombus is formed and depending upon the degree and duration of thrombus, and the degree of collateral development the fate of this thrombotic process is determined.

Arteriosclerosis↗
PubMed1993

Coronary atherosclerosis. A multifactorial disease.

BACKGROUND: Several of the theories on the pathogenesis of atherosclerosis may be integrated into a single multifactorial one. According to this theory, the most likely sequence of events involved in early atherosclerosis is vascular dysfunction and/or injury, monocyte recruitment and macrophage formation, lipid deposition, vascular smooth muscle cell proliferation (mitogenic factor mediated), and synthesis of extracellular matrix. The interaction of all these factors will configurate the typical characteristic of the atherosclerotic plaque. METHODS AND RESULTS: Accumulating experimental and clinical data suggest two pathways in atherosclerotic progression. In some cases, the very slow process of the pathogenesis of early lesions may be significantly accelerated by means of thrombus formation and organization. Thrombosis is a key process in the pathogenesis of late atherogenesis and in the development of acute ischemic syndromes. CONCLUSIONS: The possibility of retarding human atherosclerosis or even inducing its regression is one of the present therapeutic challenges. Of the different approaches to this question, one approach aims at better control of risk factors, especially plasma lipid levels. Another approach attempts to enhance the removal of lipids from the arterial wall by increasing plasma high density lipoprotein levels. Each of these approaches, by acting on the lipid-rich plaques more prone to rupture, might prevent plaque progression and induce regression to prevent acute coronary events. A third approach, based on the key role of platelet thrombus formation in the conversion of chronic to acute events, would be the use of antithrombotic therapy. This last approach may partially prevent progression of the disease.

Animals↗
PubMed1992

The clinical course of idiopathic dilated cardiomyopathy. A population-based study.

OBJECTIVE: To describe the prognosis of individuals with idiopathic dilated cardiomyopathy in a population-based sample and to compare this with the prognosis of patients in a previous referral center case series of idiopathic dilated cardiomyopathy. DESIGN: Cohort study. SETTING: Population-based in Olmsted County, Minnesota. PATIENTS: Forty residents of Olmsted County, Minnesota with idiopathic dilated cardiomyopathy initially diagnosed between 1975 and 1984 who were followed through 1 July 1989 and 104 patients from a Mayo Clinic referral case series from 1960 to 1973. MEASUREMENTS: Survival for the population-based cohort at 1 year and 5 years. RESULTS: Survival at 1 year differed dramatically between the population-based cohort and the referral case series at 1 year (95% compared with 69%, respectively) and at 5 years (80% compared with 36%, respectively) (P less than 0.001). Long-term survival for the population-based cohort was nonetheless impaired when compared with an age- and sex-matched cohort, that is, the 1980 Minnesota white population (8-year survival: observed, 58% compared with expected, 83%; P less than 0.001). Among community patients, older age (adjusted Cox model hazard ratio for 10-year increase in age, 1.59; 95% CI, 1.08 to 2.35) and lower left ventricular ejection fraction (adjusted hazard ratio for 10% decrease, 1.90; CI, 1.04 to 3.50) were independently associated with impaired survival. CONCLUSIONS: These population-based data challenge the clinical perception of the clinical course of idiopathic dilated cardiomyopathy based on referral practice prognostic studies and suggest that the clinical course of this condition may be more favorable than previously recognized.

Cardiomyopathy, Dilated↗
PubMed1992

Echocardiographic "smoke" is produced by an interaction of erythrocytes and plasma proteins modulated by shear forces.

OBJECTIVES: This study was designed to determine the blood elements responsible for spontaneous echocardiographic contrast. BACKGROUND: Spontaneous contrast or "smoke" is an echocardiographic image usually found in low flow conditions. Two blood elements, erythrocytes and platelets, have been related to the generation of smoke. METHODS: The echogenicity of porcine blood products was assessed in static and flow conditions and was graded on a digitized videodensity computer program that assigned a score of 0 for black and 100 for white images. Blood elements were circulated from a small tube (4-mm diameter) into a larger cylindric chamber (30-mm diameter) under controlled flow rate conditions. The following blood products were studied: whole blood, platelet-depleted blood, platelet-rich plasma, platelet-poor plasma, erythrocytes suspended in saline solution, adenosine diphosphate (ADP) added to platelet-rich plasma, and saline solution as a control medium. RESULTS: As blood flow was increased in 30 ml/min increments from 0 to 180 ml/min, whole blood echo videodensity (scale 0 to 100) progressively decreased in the larger tube from 38 and 42 to 20, 12, 14, 16 and 14, respectively. When flow increased from 0 to 30 ml/min in the smaller tube, corresponding to a wall shear rate of 0 to 80 s-1, the blood entering the chamber was completely echolucent. The echogenicity of blood products in the larger tube was for static flow (0 ml/min) and high flow (180 ml/min), respectively: platelet-depleted blood = 36 and 14; platelet-rich plasma = 2 and 2; platelet-poor plasma = 0 and 0; erythrocytes in saline solution = 8 and 12; ADP added to platelet-rich plasma = 0 and 15; saline solution = 0 and 0. Because platelets alone were nonechogenic but platelet-depleted blood produced a flow-dependent echogenicity similar to that produced by whole blood, platelets may not be involved in the production of smoke. However, when platelets were aggregated by ADP, they were echogenic but in dense clumps and in a flow-independent pattern not typical of the smokelike images. Erythrocytes suspended in saline solution had an intermediate density image. CONCLUSIONS: Echogenic smoke appears to be due primarily to the interaction of red blood cells and plasma proteins at low flow and low shear rate conditions.

Animals↗
PubMed1992

Unstable angina: outcome according to clinical presentation.

Unstable angina is a broad clinical diagnosis that includes patients at different levels of risk for an unfavorable outcome. Although, as in other categories of coronary artery disease, the state of left ventricular function and the extent of coronary artery disease will determine long-term prognosis, recognition of clinical markers of an early unfavorable course may be of value in defining management strategies. This review focuses on the relevance of baseline clinical characteristics and noninvasive data in assessing the prognostic significance of unstable angina in light of its presenting features. Recurrence of chest pain within 48 h after admission carries a reduction in likelihood of survival of about 20% in patients with progressive or prolonged angina. Similarly, ECG changes on admission have a negative prognostic implication, particularly in rest angina, as they predict recurrence of ischemia, myocardial infarction or need for revascularization in 80% of the patients. In variant angina, determinants of prognosis are level of disease activity, as judged by recurrence of pain, ECG changes and use of calcium channel antagonists. Patients with angina after a myocardial infarction who have more than one episode of either angina or silent ischemia in 24 h have a 10% reduction in probability of survival during the 1st year compared with that of asymptomatic patients. An abrupt course, or the rapidity with which symptoms develop, is the main determinant of prognosis in new onset angina. Thus, recurrent angina and ECG changes appear to be relevant prognostic markers in the patient subsets considered; if these are present, early coronary angiography must be performed and revascularization procedures should be considered without delay.

Actuarial Analysis↗
PubMed1992

Antithrombotic efficacy of low-molecular-weight heparin in deep arterial injury.

Low-molecular-weight heparin subfractions more specifically inhibit factor Xa than thrombin, and they may have advantages over unfractionated heparin in arterial thrombosis. The antithrombotic efficacy of four dosages of a low-molecular-weight heparin (CY216 at 100, 200, 400, or 500 Institute Choay units/kg) was compared with unfractionated calcium heparin (100 US Pharmacopeia units/kg) and placebo during deep arterial injury produced by balloon dilatation of the carotid artery in the pig. The acute thrombotic end points were 111In-labeled platelet and 125I-labeled fibrinogen/fibrin deposition and macroscopic mural thrombosis; these were related to the anti-factor Xa and antithrombin effects of the heparin preparations. Platelet deposition in segments with deep arterial injury was 42 +/- 28, 22 +/- 5, 29 +/- 12, 9 +/- 2, 9 +/- 2, and 11 +/- 3 x 10(6)/cm2 (mean +/- SEM) for pigs treated with placebo, with 100, 200, 400, and 500 units/kg CY216, and with 100 units/kg unfractionated heparin, respectively. Fibrinogen/fibrin deposition was 35 +/- 8, 19 +/- 2, 19 +/- 4, 21 +/- 3, 14 +/- 4, and 12 +/- 3 molecules x 10(12)/cm2, respectively; deposition was significantly reduced in pigs given 100 units/kg unfractionated heparin compared with placebo (p less than 0.05). Mural thrombosis was present in 74%, 45%, 30%, 14%, 5%, and 9% of deeply injured arterial segments, respectively (p = 0.02). Plasma anti-factor Xa activity and prolongation of the activated partial thromboplastin time (aPTT) with 100 units/kg unfractionated heparin were similar to that produced by 200 units/kg and 500 units/kg CY216, respectively. Thus, low-molecular-weight heparin, which predominantly inhibits factor Xa activity, was only moderately effective at reducing platelet thrombus deposition. It was less effective than 100 units/kg unfractionated heparin, except at high dosages, producing similar prolongation of the aPTT and the thrombin time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cod liver oil alters platelet-arterial wall response to injury in pigs.

In 36 normolipemic pigs randomized to a 4-week feeding with regular pig chow (n = 18, control group) or chow supplemented with cod liver oil (1 ml/kg per day) (n = 18, treated group), treatment with cod liver oil produced a significant decrease in serum cholesterol, low density lipoprotein cholesterol, and triglycerides. Deep carotid arterial wall injury (media exposed) by balloon angioplasty was associated with less 111In-labeled platelet deposition (24.6 +/- 4.8 x 10(6)/cm2 versus 62.5 +/- 17.0 x 10(6)/cm2, p less than 0.05; difference, -33.8 x 10(6)/cm2; 95% confidence interval [CI], -1.9 x 10(6)/cm2 to -73.9 x 10(6)/cm2) and injury-related vasoconstriction (21.3 +/- 2.2% versus 30.9 +/- 2.9%, p less than 0.05; difference, -9.6%; 95% CI, -2.2% to -17.0%) in the cod liver oil-treated group than in the control group; with mild injury (media not exposed), platelet deposition was low and unchanged (6.2 +/- 0.5 x 10(6)/cm2 versus 7.8 +/- 0.7 x 10(6)/cm2; difference, -1.6 x 10(6)/cm2; 95% CI, -1.1 x 10(6)/cm2 to +4.3 x 10(6)/cm2), but associated vasoconstriction was reduced respectively (16.3 +/- 2.0% versus 23.0 +/- 2.2%, p less than 0.05; difference, -6.7%; 95% CI, -0.6% to -12.8%). When arterial blood from cod liver oil-treated pigs superfused normal aortic media ex vivo, platelet deposition onto the normal aortic media was lower than when arterial blood from control pigs superfused the normal aortic media (43.7 +/- 8.8 x 10(6)/cm2 versus 66.8 +/- 13.0 x 10(6)/cm2, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1992

Clinical-pathological correlations of coronary disease progression and regression.

The initiation of atherosclerosis may result from blood flow oscillatory shear stress in certain vascular sites (bending points, bifurcations, etc.) producing chronic minimal injury resulting in functional alteration of the arterial endothelium type I injury; experimentally, this is potentiated by atherogenic risk factors such as hypercholesterolemia, hypertension, immunocomplexes, viral infections, and tobacco smoke. Such minimal injury leads to accumulation of lipid and monocytes (macrophages), and subsequently, toxic products released by the macrophages produce damage of the intimal surface with denuding endothelium type II injury or damage, which attracts platelets; all of these cells release growth factors, prompting migration and proliferation of smooth muscle cells and producing a "fibro-intimal lesion" or the outside of the capsule of a predominant "lipid lesion." The lipid lesions surrounded by a thin capsule tend to be small and rupture easily, causing type III injury or damage; that is, they are soft and weak, contain large numbers of macrophages, which may release collagenase and elastase to form abscesses, and by their location, are under the effect of flow shear forces. After plaque disruption there is thrombus formation; when thrombi are small, they can become organized and contribute to the growth of the atherosclerotic plaque; when thrombi are large and occlusive, they lead to the acute coronary syndromes. New data suggest that, at the time of plaque disruption, certain "thrombogenic" risk factors modulate the degree of thrombogenicity and, thereby, the growth of the plaque versus the various acute coronary syndromes. Aside from the need for better understanding of the basic biology of atherogenesis, emphasis on identifying and modifying the primary atherogenic and thrombogenic risk factors should continue for primary prevention. Also, new approaches should focus on the identification, stabilization, and regression of the small "lipid plaques" prone to rupture (these are not necessarily angiographically apparent), as well as on the use of better and safer antithrombotic agents for prevention of progression.

Cardiovascular Diseases↗
PubMed1992

Role of high density lipoproteins in the regression of atherosclerosis.

Atherosclerosis is a slowly progressive disease characterized by the accumulation of cholesterol within the vessel wall. Plasma lipoproteins are particles of complex lipid and protein composition that transport lipids in blood. Low density lipoproteins (LDL) and high density lipoproteins (HDL) are the major cholesterol-carrier lipoproteins. LDL seem to be responsible for the delivery of lipids (cholesterol) from the liver to the tissues. Compelling evidence supports the concept that the lipids deposited in the arteriosclerotic lesions are derived primarily from plasma LDL. The term "reverse cholesterol transport" describes the transport of cholesterol from extrahepatic tissues to the liver, where it may be metabolized. Reverse cholesterol transport seems to be the major route for removal of the exchangeable cholesterol deposited in the extrahepatic tissue. It has been postulated that a major role of the plasma HDL particle is to act as a scavenger of tissue cholesterol. The hypothesis that high levels of plasma HDL are protective against coronary artery disease (CAD) was initially proposed by Barr et al in the early 1950s, but it was overlooked until confirmed by the Tromso and Framingham studies in 1977, which showed an inverse relation between HDL plasma levels and incidence of CAD. Similar observations have been made in 15 major experimental studies including eight countries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗