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Biomedical subjects

V Fuster

Publications and source records attributed to V Fuster.

At least 325 records · Page 18Linked to original sources
PubMed1989

Platelet interaction with vessel wall and collagen in pigs with homozygous von Willebrand's disease associated with abnormal collagen aggregation.

A subgroup of pigs with von Willebrand's disease from the Mayo Clinic stock shows abnormal platelet aggregation in response to collagen [vWD-Homo(-)], in contrast to the normal aggregation responses observed in the main colony of pigs with homozygous vWD [vWD-Homo(+)]. This subgroup has been characterized at Mayo as a storage pool deficiency due to the reduced levels of ADP and Serotonin in the platelet dense granules. In the present studies, an ex-vivo perfusion chamber was utilized to investigate the deposition of 111In-labeled platelets on aortic subendothelium and collagen type I exposed to blood from vWD-Homo(-), vWD-Homo(+) and normal animals. Both non-anticoagulated and heparinized blood were exposed for wall shear rates ranging from 212 sec-1 to 3380 sec-1 and exposure times as long as 30 min. An enhanced decrease in platelet deposition in the vWD-Homo(-) animals was observed compared to vWD-Homo(+) animals. The decrease was observed primarily at the higher shear rates and was more pronounced in the absence of heparin and on the collagenous substrate. Thus, the abnormality in collagen-induced aggregation, which has been characterized as a storage-pool type defect, results in a decreased platelet deposition compared with that produced by severe vWD alone.

Animals↗
PubMed1989

Role of platelet inhibitor therapy in myocardial infarction.

Atherosclerotic plaque disruption is the predominant pathogenetic mechanism underlying the acute coronary syndromes. Plaque rupture leads to the exposure of collagen and vessel media, resulting in platelet and clotting activation, and occlusive thrombus formation. While drugs that interfere with platelet activation and function have been available for years, more powerful agents with novel mechanisms of action are being developed. Of the available platelet inhibitor drugs, only aspirin, sulfinpyrazone, and dipyridamole have undergone extensive clinical testing in patients with cardiovascular disease. More recently ticlopidine, a new and potent platelet inhibitor, has been successfully tested in patients with coronary and vascular disease. In acute myocardial infarction, aspirin significantly reduces cardiovascular mortality and reinfarction. Furthermore, the combination of aspirin and a thrombolytic agent produces maximal benefit. A role for heparin in the prevention of early mortality and reinfarction is emerging. This drug is effective for the prevention of left ventricular thrombosis in patients with anterior myocardial infarction. In the secondary prevention of reinfarction and cardiovascular mortality, available data support the use of a platelet inhibitor. Trials have shown that aspirin is as effective alone as in combination with dipyridamole, and is probably more effective than sulfinpyrazone. Long-term anticoagulant therapy also appears to be beneficial, but is associated with a high cost, need for extensive monitoring, and potential for hemorrhagic side effects. The role of aspirin in primary prevention is controversial. It may be indicated for patients at high risk for coronary disease in whom the benefit of therapy may outweigh the potential risk of cerebral bleeding. Coronary atherosclerotic plaque rupture, associated with thrombus formation, is fundamental to the development of acute myocardial infarction. Based on this concept, the role of antithrombotic therapy for the prevention or treatment of ischemic events in patients with coronary artery disease has stimulated enormous interest among clinicians and basic investigators. In this review we will examine: a) the pathogenesis of coronary thrombosis, b) the pharmacology of platelet-inhibitor agents, and c) their role in the management of patients with acute myocardial infarction and in primary and secondary prevention of cardiovascular disease. Platelets interact with both the coagulation and fibrinolytic systems in the pathogenesis of thrombosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aspirin↗
PubMed1989

The role of silent ischemia, the arrhythmic substrate and the short-long sequence in the genesis of sudden cardiac death.

To study the role of silent ischemia and the arrhythmic substrate in the genesis of sudden cardiac death, 67 patients were studied (mean age 62 +/- 12 years). Of these, 14 patients (Group 1) had an in-hospital episode of ventricular tachycardia or fibrillation while wearing a 24 h Holter ambulatory electrocardiographic (ECG) monitor, 33 (Group II) had a documented episode of sustained ventricular tachycardia or fibrillation, or both, and 20 (Group III) had angina pectoris but no ventricular tachycardia or fibrillation. Eight Group I survivors underwent programmed electrical stimulation or ECG signal averaging, or both. All Group II patients underwent 24 h Holter monitoring and ECG signal averaging to detect late potentials before programmed electrical stimulation. Group III patients underwent both 24 h Holter recording and coronary angiography. The 24 h ECG tapes were analyzed for ST segment changes, prematurity index and characteristics of ventricular premature depolarizations. Any ST depression greater than or equal to 1 mm for greater than 30 s was considered to be a reflection of silent ischemia, and the induction of ventricular tachycardia or fibrillation by programmed electrical stimulation or the presence of late potentials, or both, was considered to be a reflection of the arrhythmia substrate. Silent ischemia preceded ventricular tachycardia in only 2 (14%) of the 14 Group I patients. The prematurity index was less than 1 in only 18% of ventricular tachycardia episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Platelet inhibitor agents in cardiovascular disease: an update.

Platelets interact with the coagulation and fibrinolytic systems in the maintenance of hemostasis. However, these physiologic mechanisms may become pathologic, requiring prevention and treatment. In this review, the following clinical developments are analyzed: 1) the role of platelets in thrombogenesis; 2) the pharmacology of platelet inhibitory agents; and, most important, 3) the results of recent randomized trials of platelet inhibitor agents in different cardiovascular disorders. Aspirin reduces mortality and infarction rates in unstable angina and significantly decreases vascular mortality in acute myocardial infarction. Platelet inhibitors decrease mortality and recurrent cardiovascular events in the chronic phase after myocardial infarction. They also decrease vein graft occlusion rates after coronary bypass surgery. Although platelet inhibitors are beneficial in preventing acute vessel occlusion during coronary angioplasty, they are ineffective in preventing chronic restenosis. Antiplatelet agents, combined with warfarin, reduce thromboembolic events in patients with a mechanical prosthesis. Platelet inhibitors are also effective in secondary prevention of vascular events in patients with cerebrovascular disease. Finally, the use of aspirin for primary prevention of cardiovascular disease is still evolving, particularly in individuals at high risk. In conclusion, platelet inhibitors are effective in patients with a variety of cardiovascular disorders. The best studied, most inexpensive and least toxic agent is aspirin at a daily dose of 160 to 325 mg. Studies using new platelet inhibitor agents with different mechanisms of action are currently underway.

Aspirin↗
PubMed1989

Seasonality of births and family characteristics in a Spanish population.

The seasonality of births in the period 1871-1977 is studied in a rural north-western Spanish population. Based on a total sample of 11,695 birth registrations, temporal variation is analysed. For siblings, according to family reconstitution, the total family size, the legitimacy of the child, and birth order are considered. A coefficient of birth month dispersion is defined and estimated for each family. Intra-family variation is related to inter-family coefficients in order to determine whether the local seasonal pattern of births may be partly explained by family characteristics.

Birth Order↗
PubMed1989

Effects of thrombin inhibition on the development of acute platelet-thrombus deposition during angioplasty in pigs. Heparin versus recombinant hirudin, a specific thrombin inhibitor.

The effect of recombinant hirudin and the dosage of heparin on acute platelet-thrombus deposition during carotid angioplasty in anesthetized pigs was prospectively assessed. Fifty-five animals (mean weight, 33.9 kg) were randomized to one of six heparin dosages: heparin boluses of 35, 50, 100, 150, 200, or 250 units/kg followed by a continuous infusion of 35, 50, 100, 150, 200, or 250 units/kg/hr, respectively. Another five pigs received a bolus of 1 mg/kg hirudin (recombinant desulphatohirudin), a specific thrombin inhibitor, followed by an infusion of 1 mg/kg/hr. Bilateral carotid angioplasty was performed in all pigs 20 minutes after starting the infusion; they were sacrificed 57 +/- 12 minutes after the procedure. Deep medial arterial injury was present in approximately 75% of the dilated segments, and subendothelial injury in the remaining 25%. Mean log of number of platelets and molecules of fibrinogen per centimeter squared of deep injury in segments from all the animals treated with heparin were 4.74 +/- 1.03 and 5.02 +/- 0.64, respectively. A regression analysis showed an inverse correlation of the log of platelet deposition with the heparin group (r = -0.56, p = 0.0001) with administered total units of heparin (r = -0.55, p = 0.0003) and with mean plasma heparin concentration (r = -0.55, p = 0.0004) in deeply injured arteries. Similar inverse relations were obtained for fibrinogen. In contrast, the deposition of platelets and fibrinogen in subendothelial injury was very low and independent of the heparin administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1989

Coarctation of the aorta. Long-term follow-up and prediction of outcome after surgical correction.

The long-term clinical course was studied in 646 patients, who underwent isolated operative repair of coarctation of the aorta at the Mayo Clinic from 1946 to 1981. There were 17 perioperative deaths, and 58 patients were lost to follow-up. Of the 571 patients with long-term follow-up, 11% required subsequent cardiovascular surgery, and 25% developed hypertension. There were 87 late deaths. The mean age at death was 38 years (range, 0-67 years). Estimated survival analysis revealed 91% of patients alive at 10, 84% at 20, and 72% at 30 years after operative repair. The most common cause of late death was coronary artery disease in 32 patients, followed by sudden death, heart failure, cerebrovascular accidents, and ruptured aortic aneurysm. Age, sex, and postoperative systolic blood pressure were found to be independently predictive of survival. For patients less than 14 years of age at the time of initial coarctectomy, survival to 20 years was 91%, and for patients 14 years or older at the time of operation, survival was 79%. The best survivorship was observed in patients operated on at 9 years of age or less. The higher the postoperative systolic pressure, the higher the probability of death. This study has the largest population undergoing repair of coarctation of the aorta with a median follow-up of as long as 20 years. Four main points emerged. 1) Age at the time of initial repair is the most important predictor of long-term survival. Surgery should be offered to patients after age 1 year or sooner if hypertension is severe. 2) Coronary artery disease is the most common cause of late death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Thrombosis/platelets and other blood factors in acute coronary syndromes.

We support the concept of a common anatomic and physiologic link between the acute coronary syndromes, which consists of plaque fissuring or rupture, leading to exposure of the circulating blood to collagen, lipids, and smooth muscle cells. This, in turn, results in marked platelet activation and the initiation of the coagulation sequence, both of which lead to thrombus formation. What determines the clinical outcome in these patients is the suddenness of coronary occlusion, the completeness of blood flow deprivation, and most importantly, its duration. In unstable angina, either plaque disruption resulting in an abrupt change in its morphologic configuration with reduction of coronary blood flow or increased myocardial oxygen demand are associated with increased exertional symptoms. In rest angina, two events may take place: formation of a transient and labile thrombus due to platelet and clotting activation, or vasospasm associated with the release of platelet-derived vasoconstrictive substances or loss of endothelial relaxing properties. As a result, transient myocardial ischemia occurs, which may be intermittent and recurrent and may progress to myocardial infarction or sudden death. In myocardial infarction, plaque rupture is usually more severe, leading to the formation of an occlusive or near-occlusive thrombus which may be more persistent and fixed to the arterial wall. The duration of coronary blood flow deprivation needs to be sufficiently long in order to produce myocardial cell death. Moreover, the difference between Q-wave and non-Q-wave infarction is probably determined by the duration of blood flow obstruction, being longer in the former. The presence of a functionally adequate collateral circulation will, in part, determine the survival of the area of myocardium at jeopardy. The coronary events that take place in ischemic sudden death are probably similar to those in unstable angina, namely plaque rupture with thrombus formation. In sudden death, the resulting myocardial ischemia may precipitate fatal ventricular arrhythmias. Alternatively, platelet microemboli from ulcerated arterial plaques may produce multiple areas of myocardial necrosis which can result in electrical instability and ventricular fibrillation.

Angina Pectoris↗
PubMed1989

Value of blood-pool subtraction in cardiac indium-111-labeled platelet imaging.

Blood-pool subtraction has been proposed to enhance 111In-labeled platelet imaging of intracardiac thrombi. We tested the accuracy of labeled platelet imaging, with and without blood-pool subtraction, in ten subjects with cardiac thrombi of varying age, eight with endocarditis being treated with antimicrobial therapy and ten normal controls. Imaging was performed early after labeled platelet injection (24 hr or less) and late (48 hr or more). Blood-pool subtraction was carried out. All images were graded subjectively by four experienced, "blinded" readers. Detection accuracy was measured by the sensitivity at three fixed levels of specificity estimated from receiver operator characteristic curve analysis and tested by three-way analysis of variance. Detection accuracy was generally improved on delayed images. Blood-pool subtraction did not improve accuracy. Although blood-pool subtraction increased detection sensitivity, this was offset by decreased specificity. For this population studied, blood-pool subtraction did not improve subjective detection of abnormal platelet deposition by 111In platelet imaging.

Adult↗
PubMed1989

Necrobiosis lipoidica diabeticorum: platelet survival and response to platelet inhibitors.

Results of an open trial of platelet inhibitor treatment for necrobiosis lipoidica diabeticorum suggest the possible importance of abnormal platelet function in this disease. In ten female patients with necrobiosis lipoidica diabeticorum (six who were diabetic and four who were not) platelet survival times were measured before and after treatment with aspirin and dipyridamole. Pretreatment platelet survival time was considerably shortened in 50 percent of the diabetic and nondiabetic patients. Platelet-inhibitor treatment prolonged platelet survival time toward normal in most of these patients. The clinical response to treatment varied from healing to no noticeable effect.

Adult↗
PubMed1989

Role of von Willebrand factor in mediating platelet-vessel wall interaction at low shear rate; the importance of perfusion conditions.

We have previously observed that von Willebrand factor (vWF) plays an important role in platelet deposition on subendothelium at low values of wall shear rate (200 to 400 seconds-1). In the present study, we have investigated the mechanism responsible for such a defect in platelet deposition at low shear rates in the absence of vWF. Blood from both normal and von Willebrand's disease (vWD) animals was exposed to de-endothelialized aorta from normal pigs for a range of shear rates (200 to 3,000 seconds-1) and exposure times (three to 30 minutes) in a tubular perfusion chamber. Variations in the method of inhibiting coagulation (none, heparin, citrate, hirudin, and EDTA) and of perfusing blood (in vitro v ex vivo) were compared by determining the influence of wall shear rate and vWF on the deposition of 111In-labeled platelets on subendothelium. Whereas platelet deposition was reduced in the absence of vWF for all experimental variations at high shear rates (greater than 850 seconds-1), a defect was observed at low shear rates only when heparinized blood was exposed by means of an ex vivo perfusion system. Maximum sensitivity of the measurement occurs under ex vivo perfusion conditions due to the reduced ability of platelets to deposit in normal blood when recirculated in vitro. Our results indicate that vWF mediates platelet-vessel wall interaction even at low shear rates and that such effect can only be observed in systems where platelet function is minimally affected by the experimental conditions.

Animals↗
PubMed1989

High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits.

The effects of in vivo administration of high density lipoprotein-very high density lipoprotein (HDL-VHDL) on the development of aortic fatty streaks were studied in cholesterol-fed rabbits. The rabbits received a 0.5% cholesterol-rich diet for 8 weeks. During this period, the HDL-VHDL group was intravenously administered with 50 mg/week of homologous HDL-VHDL protein; the control group received normal saline (0.9% NaCl). HDL-VHDL fraction was obtained at density range 1.063 to 1.25 gm/ml by ultracentrifugation of normal rabbit plasma. Along the study, plasma lipid levels followed a similar profile in both groups. At the completion of the study, atherosclerotic-like lipid-rich lesions covered 37.9 +/- 6% (X +/- SEM) of the intimal aortic surface in the control group, and 14.9 +/- 2.1% in the treated group (p less than 0.001). The values of total and free cholesterol, esterified cholesterol, and phospholipids deposited within vessel wall were significantly lower in the aortas of the HDL-VHDL treated group than those in the control group. Cholesterol accumulation in the livers was also significantly lower (p less than 0.01) in the treated group than in the control. We concluded that administration of homologous HDL-VHDL lipoprotein fraction to cholesterol-fed rabbits, dramatically inhibited the extent of aortic fatty streaks and lowered lipid deposition in the arterial wall and liver without modification of the plasma lipid levels.

Animals↗