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H R Baumgartner

Publications and source records attributed to H R Baumgartner.

123 records · Page 7Linked to original sources
PubMed1969

5-Hydroxytryptamine uptake and release in relation to aggregation of rabbit platelets.

1. The aggregation of blood platelets was measured in vitro at different time intervals after the addition of 5-hydroxytryptamine (5-HT) or of reserpine to platelet-rich plasma of untreated rabbits and of rabbits injected with reserpine and 5-HT, i.e. while the platelets were taking up 5-HT or releasing it under the influence of reserpine.2. When 5-HT was added to stirred platelet-rich plasma the platelets aggregated reversibly within 1 min. The velocity of aggregation increased with 5-HT concentrations of 0.1-30 muM and decreased with higher concentrations.3. (-)-Adrenaline, which alone did not produce aggregation, markedly accelerated the aggregation caused by 5-HT. The acceleration was greatest when 5-HT and adrenaline were added simultaneously.4. 5-HT added to the platelet-rich plasma in amounts that exceeded the 5-HT capacity of the platelets progressively diminished the velocity of aggregation produced by 5-HT plus adrenaline until aggregation was completely inhibited. Smaller amounts of 5-HT produced a transient inhibition of aggregation.5. The aggregation of platelets from reserpinized rabbits was inhibited by less 5-HT than the aggregation of platelets from normal rabbits.6. (-)-Adrenaline aggregated platelets of untreated rabbits but not those of reserpinized rabbits or of rabbits injected with 5-HT when reserpine was added in vitro 1-30 min previously.7. Platelets obtained from rabbits treated first with reserpine and subsequently injected with 5-HT were not aggregated by 5-HT plus adrenaline. During incubation in vitro these platelets progressively recovered their aggregability but this recovery was delayed by the monoamine oxidase inhibitor Pargyline.8. Imipramine in concentrations which did not influence platelet aggregation by adenosine diphosphate (ADP) abolished aggregation produced by 5-HT or by 5-HT plus adrenaline.9. The inhibitory effect of adenosine on platelet aggregation was concentration-dependent and similar whether aggregation was produced by ADP, 5-HT or 5-HT plus adrenaline.10. It is proposed that aggregation brought about by 5-HT is connected with its active uptake into the platelets and is caused by ADP formed from ATP during the active uptake of the amine. When 5-HT is no longer actively taken up, it also ceases to cause or to potentiate aggregation.

Adenine Nucleotides↗
PubMedDate not supplied

Collagen type III induced ex vivo thrombogenesis in humans. Role of platelets and leukocytes in deposition of fibrin.

Exposure of type III collagen coats on plastic cover slips in parallel-plate perfusion chambers to flowing nonanticoagulated human blood resulted in deposition of platelets and fibrin. Blood was drawn directly from an antecubital vein by an occlusive roller pump over the collagen coats in chambers having flow slits of different dimensions, so that wall shear rates of 100, 650, and 2600 s-1 were obtained at 10 ml/min. Coagulation was minimally activated during the passage of blood from the vein to the chamber as shown by fibrinopeptide A levels of 3.7 ng/ml after 5-minute perfusions. The surface coverage with platelets increased from 18% at 100 s-1 to 59% at 2600 s-1, and the corresponding thrombus volumes increased from 2 to 22 microns 3/microns 2, respectively. This contrasted with the coverage with fibrin on collagen, which decreased from 28% at 100 s-1 to 9% at 2600 s-1. Fibrin deposits on the thrombi covered 6% of the surface irrespective of the shear rate, indicating that some of the deposited platelets accelerated the deposition of fibrin. The type III collagen preparation did not activate factor XII and did not possess tissue factor activity, indicating that the surface itself was not procoagulant. However, a correlation between deposited leukocytes and surface coverage with fibrin was observed (r = 0.78, p less than 0.01), suggesting a role for these cells in the deposition of fibrin. The data demonstrate that thrombogenesis is triggered by pure type III collagen, although the deposition of fibrin is not initiated by the collagen itself but presumably by deposited leukocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗
PubMedDate not supplied

Dose- and shear rate-dependent effects of heparin on thrombogenesis induced by rabbit aorta subendothelium exposed to flowing human blood.

The effect of heparin on thrombogenesis induced by the subendothelium of rabbit aorta was investigated in 24 healthy volunteers after intravenous injection of different doses (0, 1000, 2500, and 5000 IU). By using an ex vivo perfusion chamber system, the interaction between flowing blood and exposed subendothelium was measured at low (50 s-1), intermediate (650 s-1), and high (2600 s-1) wall shear rates. The low shear rate simulated blood flow in venous, the intermediate shear rate in arterial, and the high shear rate in small or stenosed arterial vessels. Deposition of fibrin, platelets, and platelet thrombi on vascular subendothelium (SE) was quantified by morphometrical and immunological techniques. Fibrin deposition prevailed at low shear rates and was only minimal at high shear rates (30 +/- 1% vs. 1 +/- 0.4% coverage of SE with fibrin, means +/- SEM, p less than 0.001). In contrast, the interaction of platelets with SE was more intense at high compared to low shear rates, as indicated by higher platelet adhesion (54 +/- 5% vs. 4 +/- 1% coverage of SE with platelets, p less than 0.001) and platelet thrombus volumes (4.8 +/- 1.3 vs. 0.5 +/- 0.1 microns 3/microns 2, p less than 0.001). Fibrin deposition on SE was inhibited by heparin in a dose-dependent manner and was abolished after high doses. In addition, high doses of heparin reduced the height and volume of platelet thrombi at low and intermediate wall shear rates, but no effect was found at the high shear rate. Our data show that heparin inhibits the formation of both fibrin and platelet thrombi on vascular subendothelium. The lack of effect of heparin on platelet thrombus formation at high shear rates indicates that thrombin modulates the growth rate and/or stability of platelet thrombi at low and intermediate shear rates, whereas additional factors may control platelet thrombus growth and stability at high shear conditions.

Adult↗
PubMedDate not supplied

Effect of aspirin and epinephrine on experimentally induced thrombogenesis in dogs. A parallelism between in vivo and ex vivo thrombosis models.

Thrombosis on the damaged or ruptured vascular wall in a stenotic coronary artery is believed to be the precipitating factor leading to unstable angina. Little is known about the nature of the interactions among platelets, fluid dynamic factors, and vessel wall properties under such conditions. In the present investigation we have compared two experimental models of thrombosis simultaneously in anesthetized dogs. The first was an in vivo model of unstable angina, in which a fixed circumflex coronary artery stenosis was produced and the resultant cyclic blood flow reductions (CFRs) through the vessel were investigated after infusion of aspirin and a combination of aspirin and epinephrine. As previously reported, aspirin inhibited the CFRs, but the continuous infusion of epinephrine reestablished the appearance of CFRs. The second was an ex vivo model, in which thrombus formation on a type III collagen surface was investigated in a parallel-plate perfusion system under controlled conditions of exposure time and flow; morphological evaluation of thrombus volume, platelet adhesion, and fibrin deposition was performed. The chamber was positioned in an extracorporeal shunt between the carotid artery and the jugular vein of anesthetized dogs and exposed to nonanticoagulated blood at a shear rate of 1,600 sec-1. Thirty minutes after establishment of the CFRs, a blood sample for platelet aggregation was collected and a bleeding time and a first ex vivo perfusion were performed. At the end of this perfusion, animals were subjected either to no treatment (n = 10) or to an intravenous bolus of 10 mg/kg aspirin (n = 7), and a second perfusion was conducted 30 minutes later. Additional untreated animals (n = 6) were given aspirin followed by a continuous intravenous infusion of 10 micrograms/ml epinephrine, and a third perfusion was conducted. Results with respect to platelet adhesion, thrombus volume, and fibrin deposition were similar in the two perfusions in untreated animals. Treatment with aspirin abolished the CFRs in all dogs and concomitantly reduced the ex vivo thrombus volume by 84% (p less than 0.01) without affecting platelet adhesion and fibrin deposition. Bleeding time increased by 40% (p less than 0.05), and collagen-induced platelet aggregation was virtually abolished (p less than 0.01). However, infusion of epinephrine in dogs after aspirin treatment restored the CFRs, and the ex vivo thrombus volumes were not statistically different from predrug values. Thus, the ex vivo model satisfactorily reflects the more complicated in vivo model events with respect to intracoronary thrombosis and substantiates the view that aspirin interrupts coronary thrombogenesis in the dog by interfering with platelet cohesion.

Animals↗
PubMedDate not supplied

Decreased coronary vascular reserve in Watanabe heritable hyperlipidemic rabbits.

Watanabe heritable hyperlipidemic (WHHL) rabbits have severe hypercholesterolemia due to a genetic defect in their low density lipoprotein receptors. Therefore, they develop severe premature atherosclerosis of the large arteries including the coronary arteries. In the present study, we measured the coronary vascular reserve of these rabbits to evaluate the total cross-sectional coronary surface area. This method allowed us to quantify the functional consequences of the coronary atherosclerotic lesions. To evaluate coronary vascular reserve, we measured coronary blood flow with the radioactive microsphere technique before and after induction of maximal coronary vasodilation by an intravenous dose of 9 mg/kg of carbocromen. A group of pure-bred WHHL rabbits was compared to a group of normal Burgundy rabbits at ages of 100 and 300 days. At 100 days, there was no difference in coronary vascular reserve between the two groups. However, at 300 days, the coronary vascular reserve in WHHL rabbits was 48% smaller than in the normal Burgundy rabbits (p less than 0.001). In addition, by making corrosion casts and morphological studies, we were able to show that at 300 days nearly all the WHHL rabbits had severe coronary atherosclerotic lesions located mainly at the origin of the large coronary arteries. We conclude that WHHL rabbits at 300 days have a severe impairment of their coronary vascular reserve due to proximal atherosclerotic lesions in the coronary arteries.

Animals↗
PubMedDate not supplied

Axial dependence of platelet-collagen interactions in flowing blood. Upstream thrombus growth impairs downstream platelet adhesion.

Vascular subendothelium and collagenous surfaces were exposed to flowing citrated blood. Platelet interactions with these surfaces were investigated at various axial distances from the upstream end of the exposed surfaces. A pronounced axial decrease in surface coverage with platelets and in thrombus dimensions was encountered on collagenous surfaces. This phenomenon was observed at shear rates of 200 to 2000 s-1, but was most pronounced at low shear rates (less than 650 s-1). After 5 minutes of perfusion at a shear rate of 650 s-1, 4.6 x 10(6) platelets were deposited on the most upstream 20 mm2 of the collagen surface, in contrast to 2.2 x 10(6) platelets/20 mm2 14 mm farther downstream. Depletion of von Willebrand factor and/or thrombospondin from the boundary layer of the blood flow was not responsible for this. Collagen-bound von Willebrand factor enhanced the surface coverage with platelets without affecting the axial decrement, while pretreatment of the collagen surface with thrombospondin had no effect at all. However, partial inhibition of thrombus growth by aspirin reduced the axial decrements, and less thrombogenic surfaces as human and rabbit subendothelium, which induced only a few small thrombi, produced virtually no axial differences in platelet adhesion. Raising the shear rate to 2600 s-1 also gave no axial differences in platelet-collagen adhesion; it did, however, give an axial increase in thrombus dimensions. This increase was neutralized after the addition of antibody against human platelet thrombospondin to the blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗