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Biomedical subjects

V Fuster

Publications and source records attributed to V Fuster.

At least 307 records · Page 17Linked to original sources
PubMed1990

Exploration of the atherosclerotic plaque.

During the past 3 decades we have achieved a better understanding of the atherosclerotic process. It has been described as a series of changes in the intima of arteries consisting of the focal accumulation of lipids, complex carbohydrates, blood and blood products, fibrous tissues, and calcium that are also associated with changes in the media. The process begins with a vascular injury that is complicated by the deposition of cholesterol esters and cholesterol. It is followed by the accumulation of lipid ladened monocytes as well as the initiation of immune mechanisms. The proliferation of smooth muscle cells into the lesion assures its permanence by the synthesis of fibrous tissue. Platelet aggregation, thrombosis and hemorrhage are all key components of plaque progression, that ultimately are associated with vascular occlusion and focal vascular spasm. Calcium plays an important role in the development of hard, ulcerated lesions. Atherosclerotic risk factors are believed to accelerate the progression of atherosclerotic plaques and the control of these risk factors may retard their proliferation and progression.

Arteriosclerosis↗
PubMed1990

Reproductive pattern in a rural Mediterranean population: La Alpujarra, Spain.

The reproductive pattern of a sample of nuclear families from La Alpujarra (Andalusia, Spain) is analysed. The origin of the wife or consanguinity of the couple does not influence fertility. Variability in number of pregnancies is most closely associated with marriage duration followed by the wife's year of birth. Differences in the number of births are explained more by the number of pregnancies than by the number of miscarriages. The number of survivors to the first birthday is dependent on the number of births and to a lower extent on infant mortality. Data from incomplete families show that reproductive performance of the wife below the age of 45 cannot be accepted as a reliable estimate of complete reproduction.

Adolescent↗
PubMed1990

Insights into the pathogenetic mechanisms of unstable angina.

Patients with unstable angina and/or non-Q-wave infarction constitute a group that is at high risk for progression to acute myocardial infarction or sudden death. Furthermore, in spite of maximal medical therapy, a large fraction of these patients experience recurrent episodes of myocardial ischemia prompting surgical revascularization or coronary angioplasty. In prior studies of patients with unstable angina, the incidence of myocardial infarction within 1 month of hospitalization was 8-13%, and the incidence of death was about 4%. Between 3 months and 1 year after presentation, the cumulative rate of infarction or death increased to 10-14 and 8-10%, respectively. That is, most recurrent ischemic events occur within the first 3 months after the onset of symptoms. In the subset of patients with pain at rest or with electrocardiographic changes at the time of admission, the prognosis is even worse. The rate of myocardial infarction or death in such patients ranged between 14 and 21% during the first 3-4 months after onset of symptoms. Crossover to surgical therapy because of recurrent ischemic pain was also common, occurring in 30-50% of the patients at 3 months. Recent advances in understanding the pathophysiology of these two syndromes suggest that an aggressive antithrombotic regimen could be of great benefit in preventing progression to acute coronary occlusion and death. Pathologic investigations strongly suggested that plaque fissuring and subsequent overlying thrombosis were the major components in the process of unstable angina progressing to myocardial infarction and/or sudden death. This hypothesis has been substantiated by recent pathologic studies of patients who died shortly after the onset of unstable angina. Examination of the coronary arteries revealed not only plaque fissuring with superimposed layers of thrombus in the majority of the cases, but also evidence of distal thromboembolism from these foci. In vivo coronary arteriography in patients with unstable angina highlighted the progression of prior coronary stenoses, even to total occlusion, and the eccentric and irregular angiographic morphology of the ischemia-producing lesions. Furthermore, intracoronary thrombus is often seen at these sites, especially when arteriography is carried out soon after rest pain. These observations also suggested that plaque rupture may have occurred. Intraoperative angioscopy has revealed ruptured plaques in patients with progressive unstable angina, while those with rest pain had complicating thrombi. Patients with unstable angina also have biochemical evidence of activation of both the coagulation systems and platelets.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina, Unstable↗
PubMed1990

Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis.

Three dosages (0.3, 0.7, and 1.0 mg/kg) of recombinant hirudin, a specific inhibitor of thrombin, were compared with heparin (50 units/kg) and placebo for reducing thrombus formation in the carotid arteries of 50 pigs after deep injury by balloon dilatation. Each drug was administered as a bolus followed immediately by a continuous infusion of the same dose per hour. Major end points were quantitative indium-111-labeled platelet and iodine-125-labeled fibrinogen deposition and the incidence of mural thrombosis. This study showed that heparin, at a dose that prolonged the activated partial thromboplastin time (APTT) to twice the control time, did not prevent mural thrombosis or significantly reduce platelet deposition compared with placebo but did reduce fibrinogen deposition. Recombinant hirudin markedly reduced platelet and fibrinogen deposition in a dose-related manner and totally eliminated mural thrombosis at an APTT of two to three times that of control. Platelet deposition (x 10(6)/cm2, mean +/- SEM) in areas of deep arterial injury for the placebo, heparin, and 0.3, 0.7, and 1.0 mg/kg hirudin groups was 54 +/- 21, 33 +/- 9, 22 +/- 6, 8 +/- 1, and 7 +/- 1, respectively; electron microscopy showed a single layer (or less) of platelets at the two highest hirudin dosages. The incidence of macroscopic mural thrombosis was 76% with placebo, 57% with heparin, 46% with 0.3 mg/kg hirudin; there were no thrombi with 0.7 or 1.0 mg/kg hirudin (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit.

The effects of homologous plasma HDL and VHDL fractions on established atherosclerotic lesions were studied in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a 0.5% cholesterol-rich diet for 60 d (group 1). Another group of animals were maintained on the same diet for 90 d (group 2). A third group was also fed the same diet for 90 d but received 50 mg HDL-VHDL protein per wk (isolated from normolipemic rabbit plasma) during the last 30 d (group 3). Aortic atherosclerotic involvement at the completion of the study was 34 +/- 4% in group 1, 38.8 +/- 5% in group 2, and 17.8 +/- 4% in group 3 (P less than 0.005). Aortic lipid deposition was also significantly reduced in group 3 compared with group 1 (studied at only 60 d) and group 2. This is the first in vivo, prospective evidence of the antiatherogenic effect of HDL-VHDL against preexisting atherosclerosis. Our results showed that HDL plasma fractions were able to induce regression of established aortic fatty streaks and lipid deposits. Our results suggest that it may be possible not only to inhibit progression but even to reduce established atherosclerotic lesions by HDL administration.

Animals↗
PubMed1990

Thrombogenesis and inhibition of platelet aggregation. Experimental aspects and future approaches.

The pathophysiology of the acute coronary syndromes and of the progression of chronic coronary artery disease is complex, but in most cases it appears to be based on fixed atherosclerotic coronary disease with plaque rupture and superimposed thrombosis commonly followed by its organization by connective tissue. Furthermore, spontaneous or therapeutic reperfusion may be followed by re-thrombosis, as it may occur in reocclusion post-thrombolysis, which is another pathologic event of significant clinical importance. The mechanisms of thrombus formation in atherosclerosis are not fully understood, but clearly involve local blood flow conditions, in addition to vascular and blood-borne factors that regulate cell-substrate and cell-cell interactions. The evolving understanding of the mechanisms of local flow and of cell-wall and cell-cell interaction is helping in the development of future approaches for the prevention and management of thrombotic events.

Animals↗
PubMed1990

Platelet inhibitor therapy. Agents and clinical implications.

Platelets are central to the pathophysiology of an array of vascular disorders. Current platelet-inhibitor drugs reduce platelet aggregation through one of three pathways but do not prevent initial platelet adhesion. The most extensive clinical experience is with aspirin, an irreversible inhibitor of cyclooxygenase. Aspirin is clinically effective and has few gastrointestinal side effects if used at a dosage of 150 to 300 mg per day. Large clinical trials have documented the benefits of aspirin in arterial thromboembolic disease. It is effective in the primary and secondary prevention of myocardial infarction, including patients with unstable angina; reduces the acute thrombotic complications of coronary angioplasty and revascularization surgery; and also reduces cerebral ischemic events in patients with cerebrovascular disease. Aspirin is less effective for thrombi arising from the venous system or intracardiac chambers, which respond well to anticoagulants. Dipyridamole and sulfinpyrazone are most effective at preventing thrombosis on prosthetic surfaces. Dipyridamole reduces emboli from mechanical prosthetic valves when combined with warfarin and, unlike aspirin plus warfarin, does not increase bleeding complications. Newer agents such as ticlopidine and the thrombin inhibitor, hirudin, appear promising but require further evaluation. Because thrombin plays a critical role in mechanisms of arterial thrombosis, its inhibition appears promising for future therapy.

Adult↗
PubMed1990

Atherosclerotic plaque rupture and thrombosis. Evolving concepts.

Rupture of an atherosclerotic plaque associated with partial or complete thrombotic vessel occlusion is fundamental to the development of ischemic coronary syndromes. Plaques that produce only mild-to-moderate angiographic luminal stenosis are frequently those that undergo abrupt disruption, leading to unstable angina or acute myocardial infarction. Plaques with increased lipid content appear more prone to rupture, particularly when the lipid pool is localized eccentrically within the intima. Macrophages appear to play an important role in atherogenesis, perhaps by participating in the uptake and metabolism of lipoproteins, secretion of growth factors, and production of enzymes and toxic metabolites that may facilitate plaque rupture. In addition, the particular composition or configuration of a plaque and the hemodynamic forces to which it is exposed may determine its susceptibility to disruption. Exposure of collagen, lipids, and smooth muscle cells after plaque rupture leads to the activation of platelets and the coagulation cascade system. The resulting thrombus may lead to marked reduction in myocardial perfusion and the development of an unstable coronary syndrome, or it may become organized and incorporated into the diseased vessel, thus contributing to the progression of atherosclerosis. In unstable angina, plaque disruption leads to thrombosis, which is usually labile and results in only a transient reduction in myocardial perfusion. Release of vasoactive substances, arterial spasm, or increases in myocardial oxygen demand may contribute to ischemia. In acute myocardial infarction, plaque disruption results in a more persistent thrombotic vessel occlusion; the extent of necrosis depends on the size of the artery, the duration of occlusion, the presence of collateral flow, and the integrity of the fibrinolytic system. Thrombi that undergo lysis expose a highly thrombogenic surface to the circulating blood, which has the capacity of activating platelets and the coagulation cascade system and may lead to thrombotic reocclusion. Measurements aimed at reversing the process of atherosclerosis via cholesterol reduction and enhanced high density lipoprotein activity are encouraging. Active research is being focused on the development of new antithrombotic tools, such as inhibitors of thrombin, thromboxane, and serotonin receptor antagonists, and monoclonal antibodies aimed at blocking platelet membrane receptors or adhesive proteins. These compounds may prove useful when immediate and potent inhibition of the hemostatic system is desired. Intensive research is still needed in the areas of pathogenesis and therapeutic intervention in atherosclerosis.

Acute Disease↗
PubMed1990

Double-blind crossover trial of diltiazem versus propranolol in the management of thyrotoxic symptoms.

We compared the efficacy of diltiazem and propranolol in a randomized, prospective, double-blind, crossover study in six patients with untreated thyrotoxicosis (mean age 31 yrs). The patients received either diltiazem 60 mg orally four times a day or propranolol 40 mg orally four times a day, each for 1 week, separated by a 3-day drug-free period. Blood pressure, heart rate, thyroid hormone levels (free T4, T3), electrocardiogram, two-dimensional and M-mode echocardiograms, and Doppler studies were performed. In addition, 8 clinical signs and 18 symptoms of thyrotoxicosis were graded. All subjects felt better with drug therapy, with three preferring diltiazem to propranolol. No significant difference in clinical response or in hemodynamic effects was noted between the agents. These data suggest that diltiazem may serve as an alternative therapy for beta blockers in controlling thyrotoxic symptoms in patients in whom beta blockade may be contraindicated.

Administration, Oral↗
PubMed1989

Antithrombotic therapy in acute myocardial infarction: prevention of venous, left ventricular and coronary artery thromboembolism.

The antithrombotic approach to patients with acute myocardial infarction in the prevention of venous, left ventricular and coronary artery thromboembolic events should be based on an understanding of pathogenesis and risk. Coronary thrombotic events involve conditions of high shear rate present in areas of vessel stenosis or disrupted atherosclerotic plaque, which lead to activation of both platelets and the coagulation system, and are best prevented by platelet inhibitors alone or in combination with an anticoagulant. However, thromboembolism that originates in the venous system or cardiac chambers is related to situations of blood stasis and low shear rate, which predominantly result in clotting activation and fibrin-thrombus formation and are best approached with anticoagulant therapy. For prevention of venous thrombosis and pulmonary embolism, early mobilization is essential and should be supplemented by low-dose heparin in patients at high risk, including the elderly and those with large infarcts, heart failure or previous thromboembolic events. For prevention of left ventricular mural thrombosis and systemic embolism, high-dose heparinization is indicated in patients with large infarcts, particularly in the anterior location and in those with heart failure. Subsequently, warfarin therapy should be considered for patients at high embolic risk, including those with echocardiographic evidence of mobile and protruding thrombi, severe left ventricular dysfunction or prior emboli. In patients with acute infarction, aspirin is recommended for preventing coronary reocclusion and reinfarction. Although anticoagulants may also be of benefit for this purpose, their use is still controversial.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗