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Biomedical subjects

H R Baumgartner

Publications and source records attributed to H R Baumgartner.

At least 73 records · Page 4Linked to original sources
PubMed1983

Decreased platelet adhesion on vessel segments in von Willebrand's disease: a defect in initial platelet attachment.

The adhesion of platelets to subendothelium exposed to flowing blood involves two distinct morphological stages: (1) platelet contact (C), the initial attachment of unspread, discoid platelets to the subendothelium, and (2) spread platelets (S), the attachment that results as contact platelets spread on the surface and become more firmly bound to it. A defect in either initial platelet attachment or platelet spreading can result in reduced levels of platelet adhesion (C + S). The combined observation of decreased platelet adhesion (C + S) and increased platelet contact (C) has been previously utilized to conclude that a defect exists in the ability of platelets to spread on subendothelium in von Willebrand's disease. In this present investigation, we demonstrate, by modeling the contact and spreading stages of platelet adhesion as a classic set of reactions in series, that the combination of reduced adhesion (C + S) and increased contact (C) is inconclusive with regard to the nature of the adhesion defect in von Willebrand's disease. Decreased adhesion (C + S) coupled with increased platelet contact (C) can result from either decreased rates of initial attachment or decreased rates of spreading. In fact, given the complexity of the temporal behavior of platelet contact (C) and platelet spreading (S), and the relatively small fraction (less than 10%) of the platelets that are in contact (C) at any time, we conclude that a determination of the nature of the adhesion (C + S) defect in von Willebrand's disease is not statistically feasible under conditions in which both contact and spreading occur simultaneously. Experiments were conducted in which blood anticoagulated with EDTA was exposed to subendothelium digested with alpha-chymotrypsin for periods of 10 and 40 min. Under such conditions, platelet spreading (S) was substantially inhibited so that the predominant platelet interaction (greater than 80%) on the subendothelium was platelet contact (C). Values of platelet adhesion (C + S) in von Willebrand's disease were significantly reduced (p less than 0.05) compared with normal values at both exposure times. Thus we conclude that the defect in platelet adhesion (C + S) in von Willebrand's disease appears to be associated with a reduced ability of platelets to attach to the surface rather than their inability to spread on the surface.

Animals↗
PubMed1981

Effect of aspirin and dipyridamole on the interaction of human platelets with sub-endothelium: studies using citrated and native blood.

The effect of aspirin and dipyridamole ingestion on the interaction of platelets with the subendothelium was studied using both citrated blood and directly sampled (native) blood. After obtained control studies, normal human subjects ingested 0.6 g of aspirin, 150 mg of dipyridamole, or a placebo and studies were repeated 1 1/2 hrs later. Subjects continued on placebo, aspirin (0.6 g b.i.d.) or dipyridamole (100 mg q.i.d.) for 6 days and studies were obtained 1 1/2 hrs after the last dose. Blood was circulated through an annular chamber on whose inner core were mounted everted segments of de-endothelialized rabbit aorta. The wall shear rate was 2,600 sec(-1). Surface coverage with adherent platelets and platelet thrombi, as well as several parameters of thrombus dimensions, were evaluated morphometrically. Aspirin ingestion markedly reduced platelet thrombi in citrated blood,--but had a much lesser inhibitory effective in native blood. Platelet adhesion was unaffected in native blood, in contrast to previous findings in which a lower shear rate (800 sec (-1)) was used. Ingestion of dipyridamole did not inhibit platelet adhesion or thrombi in either citrated or native blood. The studies indicated that, with the flow conditions used, aspirin is a relatively weak inhibitor of platelet thrombus formation in directly sampled human blood.

Adult↗
PubMed1981

Platelet adhesion and mural platelet thrombus formation on aortic subendothelium of rats, rabbits, and guinea pigs correlate negatively with the vascular PGI2 production.

This study investigates whether PGI2 produced locally by the vessel wall affects the interaction of platelets with subendothelium. Aortic endothelium was removed by a balloon catheter. Subsequent platelet deposition on subendothelium was assessed by morphometry. After 10 min exposure, surface coverage with adherent platelets in rats, rabbits, and guinea pigs amounted to 63% +/- 4, 82% +/- 3, and 97% +/- 1 (means +/- S.E.) (n greater than 5), and with microthrombi to 0 +/- 0, 6% +/- 2 and 15% +/- 4, respectively. Conversely, as measured by bioassay, excised aortic segments of rats, rabbits, and guinea pigs produced 135 +/- 14, 34 +/- 4, and less than 15 pmol of PGI2 per 10 mg of aorta per 30 min incubation in buffer, respectively (n = 4). In a second set of experiments, native blood from the aorta of a rabbit was circulated (30 ml/min) through a rat's de-endothelialized abdominal aorta and back into the vena cava of the rabbit. After a 5 min exposure at an approximate gamma w of 3000 sec-1, adhesion and aggregation of rabbit platelets on subendothelium of untreated rats amounted to 6% +/- 2 and 0 +/- 0, respectively. In contrast, on subendothelium of rats pretreated with 50 mg/kg ASA, which inhibits generation of PGI2 by greater than 80%, platelet adhesion and aggregation amounted to 55% +/- 11 and 19% +/- 7, respectively (n = 6, 2 alpha less than 0.01). The deposited thrombus volume per surface area differed by 3 orders of magnitude between the two groups. We conclude that platelet adhesion and aggregation on subendothelium correlate negatively with the generation of PGI2. Thus the smooth muscle cells of the media can produce sufficient amounts of PGI2 to locally influence the thrombogenicity of a de-endothelialized artery.

Animals↗
PubMed1980

Shear rate dependent inhibition of platelet adhesion and aggregation on collagenous surfaces by antibodies to human factor VIII/von Willebrand factor.

The effect of heterologous and homologous antibodies to factor VIII/von Willebrand factor (F.VIII/VWF) and purified VWF on the interaction of human platelets with subendothelium and with a surface consisting of collagen fibrils was investigated using annular flow chambers. Wall shear rates of 200--5200 s-1 were produced by varying the flow rate of the citrated blood which was circulated through these chambers by a pump. Surface coverage with platelets and with platelet aggregates was measured morphometrically. The antibodies had no effect on platelet adhesion at low shear rates. However, an increasing inhibition of adhesion was observed with increasing shear rates. The antibodies to F.VIII/VWF and to purified VWF virtually abolished adhesion at shear rates which are present in the microvascular (1300--5200 s-1). By contrast, antibodies to factor VIII:C which were isolated from two patients with haemophilia A had no effect on adhesion. In addition antibodies to F.VIII/VWF and to purified VWF inhibited adhesion-induced aggregation. We conclude that F.VIII/VWF plays an essential role as shear rates, i.e. when the time available for the establishment of a stable bond between platelets and collagenous surfaces is short.

Animals↗
PubMed1980

Automated microdensitometry and protein assays as a measure for platelet adhesion and aggregation on collagen-coated slides under controlled flow conditions.

A parallel-plate perfusion cell was developed for the in vitro study of platelet adhesion and aggregation. Two collagen-coated slides were exposed simultaneously to citrated blood under laminar and controlled flow conditions. The extent of the surface covered with platelets (adhesion) and platelet accumulations (aggregation) greater than about 5 micrometers in height was determined en face by automated microdensitometry of the fuchsin-stained collagen slides. The global measurement of deposited platelet protein per unit of surface was measured with a modified Lowry technique. Correlation among different parameters used to estimate the mass density on the slides, i.e., platelet number, amount of protein, and extent of platelet aggregation, is demonstrated. Acetylsalicylic acid at 100 microM decreased platelet aggregation without affecting adhesion. The new parallel-plate perfusion system offers rapid quantitation of platelet adhesion and aggregation after exposure to flowing blood.

Animals↗
PubMed1980

Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. II. Relationships among platelet adhesion, thrombus dimensions, and fibrin formation.

The adhesion of human platelets to subendothelium of rabbit aorta and the formation of microthrombi (aggregation) were investigated in an annular chamber after perfusion of native or citrated blood at wall shear rates ranging from 650 to 3300 sec-1. Previous studies demonstrated reduced adhesion and increased thrombi with native as compared to citrated blood and suggested that thrombi grow larger and higher in native blood. In the present study, thrombus dimensions were quantified by newly developed stereological techniques. The thrombus volume per surface area of subendothelium increased with increasing shear rate and was significantly greater in native blood. At 1300 sec-1 thrombi less than 5 and less than 10 micrometers in height were more frequent in citrated blood, and those greater than 20 micrometers were much more frequent in native blood. Maximum thrombus heights were 62 +/- 7 and 71 +/- 5 micrometers in native and 17 +/- 2 and 28 +/- 4 in citrated blood at shear rates of 650 and 1300 sec-1, respectively. Surface coverage with fibrin was 30%, 11%, and 0% at shear rates of 650, 1300, and 3300 sec-1, respectively. In addition, the effects of approximately 15 and approximately 45 mM citrate (final concentration in plasma) were studied at shear rates of 200, 650, and 2600 sec-1. At a citrate concentration of approximately 45 mM aggregation was abolished, and adhesion was strongly inhibited at the highest shear rate. We conclude that citrate (1) inhibits platelet attachment kinetics, thus acting to reduce adhesion, and (2) inhibits platelet aggregation and thrombus stability, thus reducing thrombus heights, which (3) may indirectly lead to increased adhesion.

Animals↗
PubMed1979

Platelet adhesion and platelet thrombus formation on subendothelium of human arteries and veins exposed to flowing blood in vitro. A comparison with rabbit aorta.

Subendothelium of blood vessel segments from elderly patients was exposed in a perfusion chamber to citrated blood under arterial blood flow conditions. The resulting platelet adhesion and thrombus formation was assessed morphometrically. The results show that the time course and the extent of platelet adhesion and aggregation were similar to the results obtained previously with subendothelium from rabbit arteries. The extent of surface-induced platelet aggregation was furthermore governed by both the properties of the exposed surface as well as those of the blood perfusate. No significant differences with regard to platelet reactivity were found between veins and arteries and the extent of surface-induced platelet aggregation was rather low.

Animals↗
PubMed1979

Effects of acetylsalicylic acid, sulfinpyrazone and dipyridamole on platelet adhesion and aggregation in flowing native and anticoagulated blood.

The interaction of rabbit platelets with subendothelium of rabbit aorta was investigated under controlled blood flow conditions. Platelet adhesion and thrombus formation were compared after perfusion of native blood and of blood anticoagulated with citrate, heparin or heparin plus citrate. 15 mM citrate in plasma caused significant reduction of aggregation, thrombus volume and thrombus height; adhesion was concomitantly increased. Heparin (500 U/kg) had no significant effect on adhesion and thrombus dimensions. Treatment of rabbits with acetylsalicylic acid or sulfinpyrazone caused a significant reduction of thrombus volume and thrombus height in the presence of citrate. However, no significant effects were observed in native or heparinized blood. It is concluded that low citrate concentrations: (1) inhibit thrombus growth; (2) enhance thrombus breakdown; (3) therefore increase adhesion, and (4) strongly enhance a possible inhibitory effect of acetylsalicylic acid and sulfinpyrazone on thrombus growth.

Animals↗
PubMed1978

Effect of shear rate on platelet interaction with subendothelium in citrated and native blood. I. Shear rate--dependent decrease of adhesion in von Willebrand's disease and the Bernard-Soulier syndrome.

Previous studies have demonstrated impaired adhesion of platelets to the subendothelium in von Willebrand's disease. These studies were performed by circulating (in a closed system) citrated whole blood through a chamber containing everted segments of rabbit aorta from which the endothelium had been removed by balloon catheter. The average wall shear rate was 800 sec-1, and the perfusion time was 10 min. In the present study we measured the interaction of platelets with subendothelium in native (nonanticoagulated) blood, using a recently described technique in which the vessel segments are perfused with directly sampled venous blood. The system was open; that is, the blood was not recirculated. We used blood flow rates of 20, 40, and 50 ml/min, which correspond to calculated shear rates of 1300, 2600, and 3300 sec-1 and perfusion times of 3, 2, and 2 min, respectively. For comparison, parallel studies at 1300 sec-1 were also obtained with citrated blood. In normal subjects, at a shear rate of 1300 sec-1, platelet adhesion was less in native blood than in citrated blood, but thrombus formation was greater. Platelet adhesion in five patients with von Willebrand's disease was decreased in both citrated and native blood. The magnitude of the adhesion defect was strongly dependent on the shear rate. Thus, in citrated blood studied at a shear rate of 1300 sec-1, adhesion was 75% less than in normal subjects, whereas in previous studies at 800 sec-1 the reduction in adhesion was 29%. In native blood, adhesion in von Willebrand's disease was normal at a shear rate of 1300 sec-1, whereas 53% and 77% reductions in adhesion were obtained at shear rates of 2600 and 3300 sec-1, respectively. The latter shear rates studied, adhesion of platelets in native blood was also decreased in the Bernard-Soulier syndrome but was normal in hemophilia and afibrinogenemia. Our findings with native blood provide further evidence that impaired adhesion of platelets to the vessel wall accounts for the hemostatic defect in von Willebrand's disease. In addition, this adhesion defect is shear rate-dependent.

Adolescent↗