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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

Exogenous prostacyclin decreases vasoconstriction but not platelet thrombus deposition after arterial injury.

OBJECTIVES: The aim of this study was to examine the in vivo effects of increasing doses of prostacyclin (PGI2) on arterial vasoconstriction, platelet deposition and their interrelation after balloon injury of porcine carotid arteries. BACKGROUND: Extensive platelet deposition and localized vasoconstriction occur acutely after arterial injury in vivo. The platelet deposition and vasoconstriction are directly correlated, and previous studies suggest that platelets may mediate the vasoconstrictive response. However, it is unclear whether vasoconstriction contributes to platelet deposition. METHODS: Seven pigs received an intravenous infusion of PGI2 at 10 ng/kg per min (PGI2 10), 8 pigs at 50 ng/kg per min (PGI2 50) and 4 pigs at 500 ng/kg per min (PGI2 500); 24 pigs with saline infusion served as a control group. RESULTS: Vasoconstriction immediately proximal and distal to the balloon-dilated carotid arterial segment where selective endothelial injury occurred was directly related to indium-111-labeled platelet deposition within the dilated segment in both control pigs and PGI2-treated pigs. However, this relation was such that for any given level of platelet deposition relative to control, PGI2 decreased vasoconstriction in a dose-related manner. None of the treatments (PGI2 10, 50 or 500) decreased quantitative 111In-labeled platelet deposition or the proportion of deeply injured arteries with mural thrombus (91%, 70% or 75%, respectively, p = NS) compared with values in control pigs (81%). Thus, vasoconstriction was directly related to platelet deposition in control and PGI2-treated animals, but vasodilation alone did not decrease platelet deposition. CONCLUSIONS: Intravenous infusion of PGI2 significantly decreases vasoconstriction but not platelet deposition or mural thrombosis after arterial injury by balloon dilation. It is therefore unlikely that vasoconstriction mediates platelet deposition in this model. At hemodynamically tolerated doses, PGI2 infusion probably will not prevent the thrombotic complications associated with angioplasty.

Animals↗
PubMed1993

The need for coronary surgery in 1993.

Coronary surgery remains an important therapeutic option for coronary revascularization, particularly in the elderly with coronary disease, in whom recent studies have demonstrated improvement of quality of life and long-term survival compared with medical treatment. Morbidity and mortality in the elderly may be predicted by stratification of preoperative risk factors into scoring systems. Interim results from multicenter trials comparing coronary surgery and coronary angioplasty for the treatment of multivessel coronary disease suggest that coronary surgery may be better for symptom relief in angina, with fewer hospital admissions and therapeutic interventions. Surgery for single- or double-vessel disease is appropriate when initial attempts at revascularization by coronary angioplasty have failed. Coronary surgery may be a therapeutic option in the treatment of cardiogenic shock, particularly in the presence of three-vessel disease or the presence of complex lesions not amenable to angioplasty. Long-term survival after myocardial infarction may be improved by revascularization of the infarct-related artery. Recent studies of myocardial viability have examined the use of positron-emission tomography scanning to determine which patients may benefit most from myocardial revascularization.

Age Factors↗
PubMed1993

Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension.

OBJECTIVE: To determine whether epoprostenol (prostacyclin, PGI2) or heart-lung transplantation (HLT), or both improves survival of patients with severe pulmonary hypertension. DESIGN: This was a prospective study where the effects of epoprostenol were compared with conventional treatment. Also, the benefits of epoprostenol and HLT were assessed by comparing survival in this group with that of 120 patients at the Mayo Clinic before HLT and epoprostenol treatment became available. PATIENTS AND INTERVENTIONS: Forty four patients were studied; 25 received continuous epoprostenol over a four year period (mean (SD) cardiac index 1.8 (0.4) 1 min-1 m-2 and mean (SD) pulmonary artery pressure (PAP) 70 (16) mm Hg) and 19 did not (cardiac index 2.1 (0.6) 1 min-1 m-2 and PAP 64 (13) mm Hg). Ten patients underwent HLT: seven had received epoprostenol, and three had not. RESULTS: The therapeutic intervention with epoprostenol, or HLT, or both improved survival compared with the Mayo clinic patients (p = 0.05). Most of the benefit was conferred by epoprostenol, which prolonged survival twofold from a median time of eight to 17 months and doubled the changes of successful HLT. The improved survival with epoprostenol was not related to its immediate capacity to cause pulmonary vasodilation. Those patients who had limited acute pulmonary vasodilation when treated with epoprostenol showed the greatest improvement in survival. CONCLUSIONS: These preliminary results indicate that those pulmonary hypertensive patients with the poorest chance of survival can be helped by epoprostenol and by HLT.

Adult↗
PubMed1993

Recombinant hirudin in patients with chronic, stable coronary artery disease. Safety, half-life, and effect on coagulation parameters.

BACKGROUND: Because the specific antithrombin hirudin prevents platelet-rich arterial thrombus and accelerates thrombolysis in a variety of animal models, it has promise as antithrombotic therapy. We therefore studied the half-life, effect on anticoagulant parameters, and safety of hirudin in patients with coronary artery disease. METHODS AND RESULTS: Thirty-eight men and 1 woman (age [mean +/- SD], 60.4 +/- 6.9 years) with angiographic coronary disease were allocated in a single-blind ascending dosage study to a 6-hour i.v. infusion of recombinant hirudin (CGP 39,393) or matching placebo. The median terminal half-life for hirudin, measured by ELISA, was 2.7, 2.3, 2.9, 3.1, and 2.0 hours for the 0.02, 0.05, 0.1, 0.2, and 0.3 mg.kg-1 x h-1 groups, respectively. Activated partial thromboplastin times (aPTT) at 3, 4, and 6 hours were averaged into a plateau value. The aPTT plateau-to-baseline ratios were 1.5 +/- 0.1, 2.0 +/- 0.1, 2.3 +/- 0.1, 2.7 +/- 0.1, and 2.9 +/- 0.1, respectively, with hirudin infused at 0.02, 0.05, 0.1, 0.2, and 0.3 mg.kg-1 x h-1. From 62% to 77% of the aPTT plateau value was seen within 30 minutes of starting the infusions and was directly related to dose. The aPTT-to-baseline ratios correlated well with plasma hirudin levels (r = .88), whereas poor correlation and sensitivity were observed between plasma hirudin levels and activated coagulation time (ACT)-to-baseline ratios (r = .44). Plasma levels of hirudin and ACT in seconds correlated overall well (r = .80), but considerable overlap occurred between baseline ACT and ACT at plasma hirudin concentrations < 1000 ng/mL. Prothrombin times were significantly prolonged only at a dosage of > or = 0.05 mg.kg-1 x h-1 and were 11.8 +/- 0.5 (INR = 1.0), 12.3 +/- 0.7 (INR = 1.1), 13.3 +/- 1.2 (INR = 1.4), 14.2 +/- 0.4 (INR = 1.7), and 15.8 +/- 0.9 (INR = 2.3) seconds for each respective hirudin dosage. Thrombin times were beyond range (> 600 seconds) at 6 hours in all except 2 patients who received the lowest dosage. All parameters returned to baseline between 8 and 18 hours after the infusion. Bleeding times were not significantly prolonged. No side effects occurred. No antibodies to hirudin were detected 2 weeks after the infusion. CONCLUSIONS: Recombinant hirudin has a terminal half-life of 2 to 3 hours. The aPTT correlates well with plasma levels of hirudin and allows close titration over a wide range of anticoagulation, while ACT and prothrombin time are relatively insensitive for monitoring hirudin administration. At anticoagulant levels effective in experimental thrombosis, a 6-hour infusion of hirudin is well tolerated and safe in a predominantly male group of patients with stable coronary atherosclerosis.

Aged↗
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↗