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Biomedical subjects

V Fuster

Publications and source records attributed to V Fuster.

At least 433 records · Page 24Linked to original sources

Comparison of the antithrombotic action of calcium antagonist drugs with dipyridamole in dogs.

Because platelet activation is associated with fluxes of intracellular calcium, calcium antagonist drugs such as verapamil and nifedipine may have useful platelet inhibitor effects. Accordingly, the effect of these drugs was compared with that of dipyridamole, an established platelet inhibitor, in preventing the deposition of indium-111-labeled autologous platelets and thrombus development in polytetrafluoroethylene (Gore-Tex) grafts interposed in both femoral arteries in mongrel dogs. Eight dogs received verapamil 7.5 micrograms/kg/min perioperatively, 8 dogs received nifedipine 4 micrograms/kg/h perioperatively, 8 dogs received dipyridamole 50 mg orally given twice during the 24 hours before operation, and 16 control dogs received isotonic saline solution perioperatively. After 3 hours of perfusion, the median weight of the grafts and luminal thrombus was less in dogs treated with dipyridamole (465.1 mg), verapamil (453.7 mg), or nifedipine (389.7 mg) than in control dogs (680.2 mg) (p less than 0.001). In addition, the estimated total platelet deposition along the graft was reduced in dogs treated with dipyridamole was reduced in dogs treated with dipyridamole (2,073.2 X 10(6)) (p less than 0.01), verapamil (1,898.9 X 10(6)) (p less than 0.001), and nifedipine (1,474.8 X 10(6)) (p less than 0.001) as compared with controls (3,056.2 X 10(6)). When the mural thrombus was removed from 14 grafts, a median 73% of the platelets were located in the interface between thrombus and graft. We conclude that all 3 drugs prevent thrombus formation by inhibiting platelet activity in this model, and that the calcium antagonist drugs are as effective as dipyridamole.

Animals↗

Noninvasive radioisotopic technique for detection of platelet deposition in mitral valve prostheses and quantitation of visceral microembolism in dogs.

A noninvasive technique has been developed in the dog model for imaging, with a gamma camera, the platelet deposition on Björk-Shiley mitral valve prostheses early postoperatively. At 25 hours after implantation of the prosthesis and 24 hours after intravenous administration of 400 to 500 microCi of platelets labeled with indium-111, the platelet deposition in the sewing ring and perivalvular cardiac tissue can be clearly delineated in a scintiphotograph. An in vitro technique was also developed for quantitation of visceral microemboli in brain, lungs, kidneys, and other tissues. Biodistribution of the labeled platelets was quantitated, and the tissue/blood radioactivity ratio was determined in 22 dogs in four groups: unoperated normal dogs, sham-operated dogs, prosthesis-implanted dogs, and prosthesis-implanted dogs treated with dipyridamole before and aspirin and dipyridamole immediately after operation. Fifteen to 20% of total platelets were consumed as a consequence of the surgical procedure. On quantitation, we found that platelet deposition on the components of the prostheses was significantly reduced in prosthesis-implanted animals treated with dipyridamole and aspirin when compared with prosthesis-implanted, untreated dogs. All prosthesis-implanted animals considered together had a twofold to fourfold increase in tissue/blood radioactivity ratio in comparison with unoperated and sham-operated animals, an indication that the viscera work as filters and trap platelet microemboli that are presumably produced in the region of the mitral valve prostheses. In the dog model, indium-111-labeled platelets thus provide a sensitive marker for noninvasive imaging of platelet deposition on mechanical mitral valve prostheses, in vitro evaluation of platelet microembolism in viscera, in vitro quantitation of surgical consumption of platelets, and evaluation of platelet-inhibitor drugs.

Animals↗

A new in vivo model of arterial thrombosis: the effect of administration of ticlopidine and verapamil in dogs.

An in vivo model of arterial thrombosis was developed in which either polytetrafluoroethylene (PTFE [Gore-Tex]) or autologous vein grafts were used to replace a segment of the femoral arteries of dogs. In one series of studies, 5 cm of PTFE and 5 cm of autologous femoral vein were used in each animal and blood flow was resumed for 1 hour. 111In-labeled autologous platelets accumulated in greater amounts on the PTFE grafts (93.6 X 10(6) platelets/cm) than on the vein grafts (2.6 X 10(6) platelets/cm) (P less than 0.001). Orally administered ticlopidine (30 mg/kg/day for 2 days), an established inhibitor of platelets, reduced platelet deposition on the PTFE grafts to 10.5 X 10(6) platelets/cm (P less than 0.01). In a second series of studies, PTFE grafts were interposed on both sides in each animal, and blood flow was resumed for 3 hours. With intravenously administered verapamil, a calcium antagonist, given perioperatively at 7.5 ug/kg/min, 12 of 16 grafts in eight dogs were patent compared with only 2 of 16 grafts in eight control dogs (P less than 0.001). Furthermore, platelet deposition on the grafts was reduced from 1,090 X 10(6) platelets/cm to 303 X 10(6) platelets/cm (P less than 0.001). Thus, both ticlopidine and verapamil are effective antithrombotic agents as a result of their inhibition of platelet activity in this model, and these results provide further evidence of a central role for calcium in platelet activation.

Administration, Oral↗

A sensitive new method of "ex vivo" platelet deposition.

In 1978, an "in vivo" quantitative method of platelet aggregation based on the increment of weight of a rabbit tendon when superfused with flowing blood (3 ml/min) derived from a carotid artery of a cat and reentering the contralateral jugular vein was reported. TO increase the sensitivity of the method, we labeled platelets with indium-111 and reinjected them after two hours; then, with a gamma counter, we quantitated the 111In-labeled platelets deposited on the superfused rabbit tendon. Results of the radioactivity method and of the weight method were compared. We found that the 111In-labeling of platelets was more precise and reproducible method, rendering possible the use of a small amount of blood without need for reentry into the venous system.

Animals↗

A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency.

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in th placebo group. This benefit in graft patency persisted in each of over 50 subgroups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation.

Adult↗

Surgical repair of Ebstein's anomaly.

Ebstein's anomaly is a complex malformation that has been treated by various surgical techniques, with variable results, since 1958. In 1972, the authors developed a repair that consisted of plication of the free wall of the atrialized portion of the right ventricle, posterior tricuspid anuloplasty, and right atrial reduction. The repair is based on the construction of a monocusp valve by the use of the anterior leaflet of the tricuspid valve, which is usually enlarged in this anomaly. Not all patients are candidates for this procedure, however, because of significant abnormalities of the anterior leaflet such as inadequate size or attachment of the free edge of the leaflet to the ventricular wall. This report describes a ten-year experience with surgical repair of Ebstein's anomaly.

Adolescent↗

Strong family history and cigarette smoking as risk factors of coronary artery disease in young adults.

This study is based on 435 consecutive patients age 50 or less who had coronary arteriography. There were 335 patients with coronary artery disease and 100 with normal coronary arteries. Risk factors reviewed were "packet-years" of cigarette smoking, family history of coronary disease in first-degree relatives 50 years of age or less, age- and sex-corrected serum cholesterol and triglycerides, hypertension, and diabetes. By univariate analysis, each risk factor except hypertension and diabetes was significantly more frequent in patients with coronary disease than in those without. By multivariate analysis of all risk factors in patients with and without coronary disease, the male or female patient with coronary disease could best be identified by the strong family history, cigarette smoking history, and age- and sex-corrected serum cholesterol. The percentage of patients with coronary disease when the three risk factors were present was 95%, two factors present 88%, one factor present 67%, none of the three 25%, strong family history alone 90%, smoking alone 66%, and serum cholesterol greater than 80th centile alone 52%.

Adult↗

Partial atrioventricular canal defect in adults.

Between March 1955 and March 1981, 52 adult patients (age 20 years or older) with partial atrioventricular canal (PAVC) were examined at the Mayo Clinic. Forty patients were in New York Heart Association (NYHA) functional class I or II. The ECG showed right bundle branch block with left-axis deviation in 48, first-degree atrioventricular block in 33 and atrial fibrillation in nine. Preoperative catheterization was done in 37 patients; the mean pulmonary resistance index was 2.8 U.m2, and the mean pulmonary-to-systemic flow ratio was 3.0. Forty-seven patients underwent operation; two required mitral valve replacement. There were three operative deaths (6.4% operative mortality) and two late deaths. All surviving patients were in NYHA class I or II. No patient required subsequent permanent pacemaker implantation. We conclude that repair of PAVC in adults may be performed at low risk and may improve patient longevity and functional status.

Adult↗

Arteriosclerosis in normal and von Willebrand pigs: long-term prospective study and aortic transplantation study.

In a long-term prospective study, five normal control pigs and five pigs with homozygous von Willebrand's disease received a nonfatty diet from age 3 months to 4 years; then the aortas were analyzed. The fibrous arteriosclerotic plaques in the distal abdominal aortic region involved an average of 28% of the surface area in control pigs and only 7% of the surface area in pigs with von Willebrand's disease (P less than 0.01). In a subsequent study of 3-month-old pigs, the distal abdominal aortic segments from nine normal pigs were cross-transplanted with segments from nine other normal pigs (control study), and aortic segments from four normal pigs were transplanted into four host pigs with von Willebrand's disease (exchange study). All pigs received a 2% cholesterol diet for up to 6 months; then the transplanted aortic segments were analyzed. The donor normal aortic segments in the host normal pigs developed arteriosclerosis that involved an average of 20% of the surface; the endothelial fluorescent pattern of von Willebrand factor was identified. In contrast, the donor normal aortic segments in the host pigs with von Willebrand's disease had arteriosclerosis that involved an average of only 4% of the surface (P less than 0.01); the endothelial cell von Willebrand factor was not identified. The long-term prospective study indicates that pigs with von Willebrand's disease are resistant to the development of spontaneous arteriosclerosis. The aortic transplantation data are compatible with the hypothesis that the absence of von Willebrand factor in pigs with von Willebrand's disease may cause impairment of platelet-arterial wall interaction and resistance to arteriosclerosis.

Animals↗

Imaging of platelets in right-sided extracardiac conduits in humans.

As a connection between the systemic venous ventricle and the pulmonary artery, valved Dacron extracardiac conduits have remarkably influenced the surgical approach to many complex congenital heart defects. Obstruction of the conduit, however, can reduce the long-term effectiveness of this corrective procedure. In addition to stenosis of the porcine valve, formation of thick fibrous neointima plays a major role in the pathogenesis of conduit obstruction. The purpose of this study was to determine whether platelet deposition could be demonstrated in these conduits by external imaging with In-111-labeled autologous platelets. After injection of labeled platelets either immediately after operation or on the fifth to eighth postoperative day, imaging was performed by standard procedures. Eight of nine patients had platelet accumulation in the conduit, and treatment with aspirin and dipyridamole caused no recognizable change in platelet deposition. This study demonstrates the feasibility of imaging platelet deposition in Dacron conduits and shows that the pattern of deposition varies with time.

Adolescent↗

Systemic thromboembolism in mitral and aortic Starr-Edwards prostheses: a 10-19 year follow-up.

Our study comprised 302 consecutive patients seen between 1962 and 1971 who underwent mitral (MVR) (132 patients) or aortic valve replacement (AVR) (170 patients) with a Starr-Edwards prosthesis because of advanced mitral or aortic incompetence. The follow-up interval was 10-19 years. For more recent valve models (1200/1260 aortic or 6120/6310 mitral), the probability of a surviving patient remaining free of systemic thromboembolism after 10 years was 70% for MVR and 74% for AVR. The probability of freedom from thromboembolism was less than this for the earlier valve models; the probability for the entire group at 10 years was 66% and at 15 years was 58%, with no significant difference between AVR and MVR. About one-fourth of the patients with an embolism (20% MVR, 27% AVR) had more than one embolic event. Of all emboli, most (86% MVR, 84% AVR) were cerebral, about half (48% MVR, 57% AVR) left a neurologic deficit, and about one-tenth (11% MVR, 10% AVR) led to death. Of the predictive factors reviewed, the incidence of emboli was significantly higher only in patients with MVR considered to have inadequate anticoagulation (p less than 0.01) and in patients receiving model 6000 mitral prosthesis (p less than 0.02). This long-term follow-up study of patients with a Starr-Edwards prosthesis reveals that systemic embolism is a persistent and significant problem.

Adolescent↗

In vivo platelet survival in rheumatoid arthritis.

We studied the in vivo consumption of chromate-labeled platelets in 14 patients with active rheumatoid disease and demonstrated shortened platelet survival in 8. We were unable to find significant relationships between diminished platelet survival and clinical features (including vasculitis), the presence of circulating immune complexes (as measured by both a monoclonal rheumatoid factor and the Raji cell assays), the presence of intravascular coagulopathy with fibrinolysis (as measured by the protamine gel test), other laboratory variables commonly obtained in rheumatoid patients, or various drug regimens.

Adult↗

Daily and seasonal variation in sudden cardiac death, Rochester, Minnesota, 1950-1975.

Incidence cases of coronary heart disease that occurred in Rochester, Minnesota, during the years 1950 through 1975 were used for a study of the distribution of sudden cardiac death (1,054 cases) by day of the week and season of the year. Overall, sudden cardiac death--that is, death within 24 hours of onset of symptoms--occurred with greater frequency on Saturdays than on other days of the week. The frequency of occurrence of sudden cardiac death by season varied somewhat--the highest frequency was in winter and the lowest in summer-- but no more than expected by chance. Among males, there was a decreasing trend by day of the week from Saturday to Friday, and this was so for those with and those without a history of coronary heart disease (P less than 0.01).

Coronary Disease↗

The role of Willebrand factor in platelet - blood vessel interaction, including a discussion of resistance to atherosclerosis in pigs with von Willebrand's disease.

Von Willebrand pigs have all the manifestations of the severe human disease. The role of Willebrand antigen (VIII R:AG) and ristocetin cofactor (VIII: RWF) was assessed in these pigs by (1) transfusion and (2) "in vitro" bleeding time assay. The skin bleeding time became normal when the level of transfused Willebrand factor (VIII R:AG/RWF) was raised in the plasma above 30 U/dl. After single or repeated transfusions, skin capillary endothelium and platelets were still distinguished from normal by VIII R:AG deficiency. When incisions in excised porcine skin ("in vitro" bleeding time) were perfused with blood and plasma fractions, haemostasis occurred when plasmatic Willebrand factor exceeded 30 U/dl whether the skin or platelets came from normal or from von Willebrand pigs. The platelet plug occluding the skin incision contained VIII R:AG by immunofluorescence. Willebrand factor appears to coat surfaces and to serve as a platelet attachment protein. These bleeder pigs are resistant to atherosclerosis. If platelets are involved in early atherosclerotic lesions, the role of Willebrand factor in platelet - blood vessel interaction may be important.

Animals↗