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Biomedical subjects

V Fuster

Publications and source records attributed to V Fuster.

At least 271 records · Page 15Linked to original sources
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↗
PubMed1992

Endothelium and atherosclerosis.

PURPOSE: To review the effect of damaged endothelium on the development of atherosclerotic disease. BACKGROUND: Atherosclerotic cardiovascular disease is a complex problem involving lipid deposition, blood pressure, rheologic forces, carbohydrate tolerance and thrombogenic factors. The loss of functional, if not structural, integrity of the vascular endothelium is closely related to the initiation of atherosclerosis. The endothelium contributes to local vascular regulation. Normal endothelial cells are thrombo-resistant; they prevent leukocyte adhesion and control vascular tone by converting angiotensin I into angiotensin II, inactivating bradykinin, norepinephrine, serotonin and ADP, and by secreting vasodilator substances, such as prostacyclin and endothelium-derived relaxing factor (EDRF), and contracting factors such as endothelin. Endothelin is a potent vasoconstrictor peptide that increases intracellular calcium, causing a rapid and transient increase in c-fos and c-myc messenger (m)RNA levels and DNA synthesis in rat vascular smooth muscle cells. In isolated vessel segments, altered endothelial vasoreactivity is usually demonstrated following mechanical trauma to the endothelium. METHODS AND RESULTS: We investigated the function of normal and damaged endothelium in pigs, following superficial balloon injury, which produces a significant alteration in endothelium-dependent coronary vasoreactivity. The anesthetized pigs were given an intracoronary (left anterior descending artery) infusion of acetylcholine. The balloon injury caused a local transient spasm while the distal uninjured vessel did not change. When acetylcholine was given before the balloon injury, the diameter of the left anterior descending artery did not change, even after preconstriction in vivo with prostaglandin (PG) F2 alpha, but acetylcholine given after the balloon angioplasty caused dose-dependent vasoconstriction. It is known that vasoconstriction in arteries can reduce blood flow and increase arterial wall-shear forces, which increase platelet deposition in injured arteries and may precipitate rupture of atherosclerotic plaques. CONCLUSION: The intact endothelium is one of the greatest sources of protection from arterial thrombosis, atherosclerosis and vasoconstriction.

Acetylcholine↗
PubMed1991

Clinical and angiographic characteristics and outcome of patients with rest-unstable angina occurring during regular aspirin use.

Today many patients admitted with an acute coronary syndrome are already taking aspirin. Because they have symptoms despite antithrombotic therapy, these patients are presumed to be at higher risk for subsequent clinical events. In a pilot trial of antithrombotic therapy in patients with unstable angina at rest or non-Q wave infarction, 93 patients admitted within 48 h of pain were prospectively followed up for 12 weeks. On admission, 29 patients (31%) were already taking daily aspirin; 64 (68%) were receiving no antiplatelet agent. After enrollment all patients received antithrombotic therapy with either aspirin or heparin according to protocol regardless of prior aspirin use. The two groups (prior users versus nonusers of aspirin) were similar with regard to age, gender, coronary risk factors, prior antianginal medication, duration of symptomatic coronary disease, presentation with non-Q wave infarction and extent of electrocardiographic changes on admission. Quantitative analysis of coronary arteriograms (on a 0 to 10 scale) showed similar myocardium-in-jeopardy scores (JS). Follow-up events (recurrent ischemia [Isch], infarction [MI] and revascularization [Revasc]) were: (formula: see text) Aspirin users experiencing rest angina are similar to other patients with ischemic rest pain. The "resistant to aspirin" group does not constitute a subgroup that is at higher risk for cardiac events or revascularization.

Adult↗
PubMed1991

Plaque disruption and thrombosis in unstable angina pectoris.

Therapeutic strategies and clinical trials in unstable angina should be based on the pathogenesis, risk, and mechanisms of thrombosis. The mechanisms of thrombosis and the differences in the effects of anticoagulant, antithrombotic, antifibrin, and antiplatelet drugs must be taken into account when determining the dosage and duration of therapy. Ignoring these principles may prevent identification of new therapy, increase the cost of new drug development and research, increase the cost of new drugs, and increase the cost of medical care.

Angina, Unstable↗
PubMed1991

Pathogenesis of thrombosis in unstable angina.

Plaque rupture of the thinned, weak fibrous cap infiltrated by macrophages and overlying a pool of lipid in the arterial wall initiates the acute thrombotic event of unstable angina. Thrombosis may be advanced within minutes. Most lesions that precede plaque rupture are minor (less than 50% stenosis); thus, thrombus greatly contributes to sudden flow limitation and onset of symptoms. If thrombosis can be totally blocked (not possible with current antithrombotic agents), clinical events should be preventable, and endogenous thrombolysis may be possible within days. Local and systemic factors contribute to arterial thrombosis. With type III injury (fissure into plaque or media) platelet-rich thrombus anchors in the fissure, tracks along the site of deep injury, extends into the lumen, and requires the highest blood level of specific thrombin inhibition (a molar concentration that inhibits the total concentration of prothrombin in circulating blood). Thus, the thrombin content requiring inhibition in type III injury is highest. Local factors for thrombosis associated with type III injury include the rheology of blood flow (increased shear rate forces platelets to the periphery) and substrates in the arterial wall. Plaque substrates include the more thrombogenic collagens (types I and III and diabetic or glycosylated collagen), tissue thromboplastin, lipid gruel, thrombin bound to arterial wall matrix, and decreased prostacyclin. There is a direct relation between platelet deposition (thrombus) and local vasoconstriction, which may perpetuate each other. Thrombus as a substrate is more thrombogenic than type III arterial injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina, Unstable↗
PubMed1991

Thrombin regulation of platelet interaction with damaged vessel wall and isolated collagen type I at arterial flow conditions in a porcine model: effects of hirudins, heparin, and calcium chelation.

The role of thrombin inhibition in platelet vessel wall interaction and thrombus growth was studied under controlled flow conditions. Natural hirudin and recombinant hirudin (r-hirudin), which are specific thrombin inhibitors, were compared with heparinized blood (1.8 +/- 0.2 U/mL) and Ca(2+)-chelated blood in their potential to inhibit platelet interaction and thrombus growth on two biologic vascular surfaces and one immobilized vessel wall component. The substrates were perfused by flowing blood at shear rates typical of patent and stenosed arteries (212 to 1,690/s) for 5 minutes. Platelet deposition was measured by In-111-labeled platelets. We found that both natural and r-hirudin have similar effects on platelet-substrate interaction. As compared with heparin, platelet deposition to mildly damaged vessel wall and digested collagen type I was not reduced by hirudin or citrate. However, hirudin and citrate significantly reduced platelet deposition to severely damaged vessel wall (platelets x 10(6)/cm2: 93 +/- 10 in heparinized blood v 50 +/- 7 in blood treated with 100 U/mL r-hirudin). Therefore, thrombus growth on areas of severe wall damage is in part dependent on local thrombin production at the site of vascular damage. We also found that hirudin added to heparinized blood reduced platelet deposition to severely injured wall but not to subendothelium or collagen-coated slides. Hirudin added to citrated blood did not affect platelet deposition. Our study indicates that local thrombin generation at the site of severe injury will induce platelet activation and deposition even in the presence of average therapeutic heparin levels that inhibit blood coagulation.

Adenosine Diphosphate↗
PubMed1991

Usefulness of ST-segment changes in greater than or equal to 2 leads on the emergency room electrocardiogram in either unstable angina pectoris or non-Q-wave myocardial infarction in predicting outcome.

To determine the reliability of the admission electrocardiogram in predicting outcome in patients hospitalized for chest pain at rest, 90 patients were randomized into a trial of aspirin versus heparin in unstable angina or non-Q-wave myocardial infarction, and prospectively followed for 3 months. The emergency room admission electrocardiogram was analyzed for ST-segment deviation greater than or equal to 1 mm/lead and T-wave changes. Unfavorable outcomes were recurrent ischemic pain, myocardial infarction and coronary revascularization with angioplasty or surgery. In patients who underwent coronary arteriography, a myocardium in jeopardy score ranging from 0 to 10 was assigned, based on the number of vessels with a diameter stenosis greater than or equal to 70% and the location of the stenoses. Considering all 90 patients, an admission electrocardiogram with ST-segment deviation in greater than or equal to 2 leads had a positive predictive value for adverse clinical events of 79% and a negative predictive value of 64%. In the subset of patients without left ventricular hypertrophy and whose admission electrocardiograms were recorded during chest pain (62 of 90), the positive predictive value of ST deviation in greater than or equal to 2 leads improved to 89% and the negative value to 72%. Of the 62 patients, 53 underwent coronary arteriography. There was a positive linear correlation between the total number of leads with ST-segment deviation and the myocardium in jeopardy score (r = 0.80, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Acute biologic response to excimer versus thermal laser angioplasty in experimental atherosclerosis.

Vascular injury and platelet accumulation after balloon angioplasty are two potentially important triggers of the process of restenosis that may be minimized by the use of laser energy to ablate atherosclerotic plaque. The type of laser most suitable to achieve these goals remains unknown. Accordingly, angiographic and histologic studies and quantitative platelet deposition analysis were performed on 27 atherosclerotic rabbit iliac arteries randomized to treatment with excimer laser or thermal laser angioplasty. Excimer laser angioplasty was achieved with 35 to 40 mJ/mm2 of 308 nm xenon chloride irradiation delivered through a 4.5F catheter made of 13 concentrically arranged 200 microns fiber optics, at a repetition rate of 25 to 30 Hz and a pulse duration of 135 ns; thermal laser angioplasty was achieved with a 1.7 mm metal probe heated with 10 W of continuous wave argon laser energy. The baseline and post-laser luminal diameters of excimer laser-treated vessels (0.92 +/- 0.28 and 1.56 +/- 0.48 mm, respectively) were similar to those observed in thermal laser-treated vessels (1.05 +/- 0.44 and 1.61 +/- 0.41 mm, respectively). Perforation occurred in 4 (29%) of 14 thermal laser-treated arteries and in 0 of 13 excimer laser-treated arteries (p = 0.04); spasm was observed in only 1 thermal laser-treated vessel. On the basis of a quantitative histologic grading scheme (damage scores of 0 to 4), greater degrees of injury were measured in thermal versus excimer laser-treated vessels (2.4 +/- 1.0 versus 1.3 +/- 0.4, p = 0.009).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Laser↗
PubMed1991

Antithrombotic therapy in the coronary vein graft patient.

Coronary artery bypass grafting is an important therapeutic modality in the treatment of the patient with coronary artery disease; however, long-term results are limited by the development of saphenous vein graft disease early and late after operation. The pathogenesis of early vein graft occlusion is primarily thrombotic, while that occurring later frequently involves thrombosis superimposed on intimal hyperplasia or vein graft atherosclerosis. We describe the role of various platelet inhibitors and anticoagulants in the prevention of saphenous vein graft occlusion following coronary artery bypass grafting.

Coronary Artery Bypass↗
PubMed1991

The role of platelets, thrombin and hyperplasia in restenosis after coronary angioplasty.

Coronary angioplasty has become a successful and widely used treatment for patients with coronary artery disease since its first clinical application in 1977. The primary success rate has improved despite the increase in procedure and case complexity. However, acute reocclusion and late restenosis, which constitute the most important problems after successful angioplasty, continue to occur in about 5% and 35% of patients within 3 to 6 months, respectively. Angioscopic and pathologic observations have suggested that a multifactorial pathophysiologic process accounts for acute reocclusion, involving marked thrombosis, intimal dissection, medial and subintimal hemorrhage, vascular recoil and vasocontriction. In contrast, chronic restenosis involves the development of fibrocellular intimal hyperplasia within a milieu created by vascular injury, platelet activation, thrombin generation and the release of mitogens. Although current pharmacologic approaches, which involve antithrombotic and anticoagulant therapy, have been largely ineffective in eliminating acute reocclusion and chronic restenosis, recent advances in the research in thrombosis, platelet receptors and smooth muscle growth regulation have allowed new therapeutic options to be tested in the experimental setting, with subsequent potential clinical applications in patients.

Angioplasty, Balloon, Coronary↗
PubMed1991

Importance of antithrombin therapy during coronary angioplasty.

Angioplasty procedures with balloons, cutters or lasers all may greatly enlarge the arterial lumen, but luminal diameter may decrease because of mural thrombus in 70% to 80%, smooth muscle proliferation, vasoconstriction or recoil. Thrombin binds to arterial wall matrix and fibrin within a thrombus. Heparin dose-dependently decreases platelet and thrombus deposition but does not eliminate these even at high doses. Specific thrombin inhibition started before angioplasty experimentally prevents mural thrombus and limits platelet deposition to a single layer or less. Experimentally, anticoagulant and antifibrin effects occur at lower antithrombin blood levels and lower activated partial thromboplastin times (1.7 times control). Because platelets are so sensitive to thrombin, the higher level of thrombin inhibition required may occur at a specific level (activated partial thromboplastin time greater than or equal to 2 times control); this is not defined in humans. The duration of therapy is not defined in animals or humans. Thrombus and thrombin may be related to cellular proliferation.

Angioplasty, Balloon, Coronary↗
PubMed1991

The porcine model for the understanding of thrombogenesis and atherogenesis.

The hypothesis originated by Carl Rokitansky a century ago that thrombosis contributes substantially to atherosclerosis has been rekindled by accumulating experimental and clinical evidence. On the basis of our experience with the experimental porcine model, several important biologic determinants of thrombosis have been identified. The degree of vascular injury seems to be the primary determinant of the thrombotic response. In addition, hemodynamic shear stress and the presence of the von Willebrand factor have important roles in the process of thrombosis. Although there is little evidence that thrombosis is a factor in the initiation of spontaneous, or naturally occurring, atherosclerosis, substantial evidence suggests that thrombosis has an essential role in the progression of spontaneous atherosclerosis and also in the early pathogenic process of the syndromes of accelerated atherosclerosis-namely, heart transplant atherosclerosis, vein graft disease, and coronary restenosis after angioplasty. Advances in the understanding of vascular injury and of the interactions of blood cells with the vascular wall have allowed development of new experimental antithrombotic strategies and subsequent clinical applications in the prevention of these vascular diseases.

Angioplasty, Balloon, Coronary↗