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H K Breddin

Publications and source records attributed to H K Breddin.

At least 73 records · Page 4Linked to original sources
PubMed1991

Anticoagulant and antithrombotic effects of combinations of defibrotide with heparins and other antithrombotic agents in an animal thrombosis model.

Defibrotide, acetylsalicylic acid, low molecular weight heparin (CY 216), sodium heparin, Molsidomin and a thromboxane receptor antagonist have been investigated separately and in combinations in an animal thrombosis model in which rat mesenteric venules are damaged by defined laser energy. Furthermore, the ex vivo anticoagulant activity of Defibrotide and heparin were studied in rat plasma. All investigated agents showed a significant and dose-dependent antithrombotic effect when venules were damaged. A strong additive effect was observed when Defibrotide was administered together with heparins. The combinations of Defibrotide with other antithrombotic agents did not have significant additive effects. In the present study the combination of Defibrotide and heparins showed a prolongation of aPTT and Heptest in comparison with heparin given exclusively.

Animals↗
PubMed1991

Effects of different hirudins and combinations of low doses of hirudin, heparin and acetylsalicylic acid in a rat microcirculatory thrombosis model.

Two recombinant hirudins (r-hirudin), natural hirudin and hirudin in combination with heparin or acetylsalicylic acid (ASA) have been studied in a thrombosis model in which rat mesenteric venules of a diameter of 20-30 microns were injured by well-defined argon laser lesions. In the animal model all hirudins showed significant and dose-dependent antithrombotic effects in doses between 0.05 and 0.1 mg/kg after single intravenous and subcutaneous injections. The antithrombotic effect of single (0.2 mg/kg i.v. or 0.1 mg/kg s.c.) injections lasted longer than 4 h (i.v.) or 6 h (s.c.). Hirudin at a dose of 0.1 mg/kg and heparin at doses of 0.05 mg/kg showed a significant antithrombotic effect 2 h after subcutaneous injection. When heparin and hirudin were injected together at this dosage, the effect of the combination was in the same range as that of unfractionated heparin or hirudin alone. An additive antithrombotic effect was observed if a low dose of r-hirudin (0.1 mg/kg) was combined with a moderate dose of ASA (10 mg/kg).

Animals↗
PubMed1991

Comparative study of three recombinant hirudins with heparin in an experimental venous thrombosis model.

Three recombinant hirudins (r-hirudins) produced by genetic processes from Escherichia coli and yeast were studied. r-Hirudins could be an alternative treatment to heparin; so, the antithrombotic activity of these drugs should be compared to heparin, the reference substance, in an experimental venous thrombosis model. In this model, the effect of these r-hirudins on thrombus weight reduction were not identical. They varied depending on the original product (E. coli or yeast). The growth-inhibiting activity of r-hirudins on existing thrombi is not dose dependent, whereas that of heparin is. Moreover, in the conditions of this study, higher doses of heparin, but not of hirudins, increased the bleeding time. Although hirudin has limited applications for the time being, it seems an interesting anticoagulant drug, and the availability of r-hirudin opens new therapeutic anticoagulation perspectives.

Animals↗
PubMed1991

The effects of recombinant hirudin on various platelet functions.

The effect of two recombinant hirudins, HBW 023 (Hoechst AG, Frankfurt, FRG) and CGP 39393 [recy(tyr 63)] (Ciba Geigy, Basel, Switzerland) on various platelet functions has been investigated in blood samples of healthy volunteers anticoagulated with hirudin at concentrations of 10, 30, 50 micrograms/ml blood. Spontaneous aggregation was rarely observed in hirudinized platelet-rich plasma (PRP) compared to citrate-PRP. In comparison with citrate-PRP, both hirudins reduced the maximal response to epinephrine, but had no influence on the maximal response to ADP. Both hirudins reduced platelet adhesion to siliconized glass and inhibited platelet spreading compared to citrate-PRP. If hirudin was added to citrate-PRP, platelet count, epinephrine-induced aggregation, platelet spreading and adhesion remained unchanged while the maximal response to ADP increased. If citrate was added to hirudin-PRP, the maximal response to epinephrine as well as platelet spreading and adhesion increased to the extent observed in citrate-PRP. The effects of hirudin on platelet function are more pronounced than those of unfractionated heparin.

Adenosine Diphosphate↗
PubMed1991

Effect of recombinant hirudin on cytosolic Ca2+ concentrations using different platelet stimulators.

Cytosolic Ca2+ concentration, [Ca2+]i, and aggregation behavior of hirudinized platelet suspensions were examined under stimulation with thrombin, adenosine diphosphate, platelet-activating factor, collagen and the calcium ionophore, ionomycin. A rise in [Ca2+]i, a key step in platelet activation, was only inhibited by recombinant hirudin r-hirudin using the agonist thrombin. All other stimulators including ionomycin were not affected by r-hirudin. If hirudinized blood was gel-filtered before platelet stimulation, thrombin induced the same response as citrated platelet suspensions. Aggregation studies and calcium influx using various stimulators showed good correlation: only thrombin-induced aggregation was completely inhibited by r-hirudin. These results support the hypothesis that hirudin inhibits platelet function by thrombin binding and not by direct interaction with platelets.

Adenosine Diphosphate↗
PubMed1991

[Antithrombotic effects of molsidomine alone and in combination with other antithrombotic agents in a thrombosis model of the microcirculation of the rat].

The antithrombotic effect of Molsidomin and other different antithrombotic agents have been investigated alone and in combinations in a thrombosis model in rats in which mesenteric vessels with a diameter of 20-30 microns were injured by defined argon laser lesions. In this animal thrombosis model all agents showed a significant and dose-dependent antithrombotic effect. A strong additive effect was observed when Molsidomin was infused together with Cicaprost. A similar additive effect was observed after administration Molsidomin together with heparins. The combination of a minimal effective dose of Molsidomin with Aprosulate also had a significant additive effect. After application of Molsidomin together with a TXA2 receptor antagonists a slight additive antithrombotic effect was observed.

Animals↗
PubMed1991

[Thrombocyte function in children with Type I diabetes mellitus. Cross-sectional study].

Platelet count, spontaneous platelet aggregation, ADP- and collagen-induced platelet aggregation platelet adhesion, platelet volume, shape change, beta-thromboglobulin and von-Willebrand-factor have been investigated in 51 insulin dependent diabetic children without clinical signs of diabetic angiopathy. Compared to an age matched healthy control group diabetic children showed a significant enhancement of spontaneous platelet aggregation, elevated plasma levels of von-Willebrand-factor, increased platelet shape change and adhesion. No alterations could be found in ADP--and collagen--induced platelet aggregation and in beta-thromboglobulin levels. Significant correlations could be found between the total glycosylated haemoglobin concentrations (Hb A1) and spontaneous platelet aggregation, as well as between duration of diabetes Hb A1, and platelet volume. In this study we could demonstrate changes in platelet function in diabetic children without clinical signs of diabetic angiopathy. However these changes could be due to metabolic adjustment and may precede diabetic vasculopathy.

Adenosine Diphosphate↗
PubMed1991

[Inhibition of induced thrombocyte aggregation in the presence of endothelial cells by dipyridamole].

Dipyridamole is widely used as a platelet function inhibitory drug. Its effect on platelet aggregation was investigated in a newly developed system, in which platelet aggregation was carried out in the presence of a human endothelial cell monolayer (EC). After iv. injection of 20 mg Dipyridamole platelet aggregation (inducer ADP 5 microM, Collagen 5 micrograms) was totally inhibited. The EC dependent antiaggregatory effect of Dipyridamol could be abolished if EC's were pretreated with 1 mmol ASA for 30 min. Our results, carried out in PRP demonstrate that Dipyridamole inhibits platelet aggregation even in the absence of red blood cells which were supposed to enhance the antiplatelet effect by their reduced adenosine uptake. Anenhanced PGI2 production in the EC's may explain the aggregation inhibiting effect of Dipyridamole in this test system.

Culture Techniques↗
PubMed1991

[Effect of SIN 1 on the interactions of endothelial cells and thrombocytes].

A new method has been developed to investigate the direct effect of endothelial cells on platelet aggregation in the presence of cultured confluent human EC monolayers. The inside of the disk shaped cuvettes are covered by human umbilical vein ECs. The cuvettes rotate in the light beam of a photometer. In these cuvettes the effect of different aggregation inducers was inhibited in a concentration-dependent manner, e. g. for collagen at 0.5 microgram/ml, ADP at 5 x 10(-7) M, epinephrine at 5 x 10(-7) M and thrombin at 0.05 U/ml final concentration. (Platelet count 5 x 10(5)/microliters). Higher concentrations of the inducers led to irreversible platelet aggregation and were used for testing of antiplatelet drugs. In this system we detected a synergism between the antiaggregatory effect of the EC monolayer and that of SIN 1 (Cassella, Frankfurt/Main) the main metabolite of Molsidomine. 10 micrograms/ml PRP of SIN 1 alone partially inhibited platelet aggregation induced by 1 microgram/ml collagen and 10(-6) M ADP respectively in uncovered aggregation cuvettes. In the presence of an EC monolayer complete inhibition of platelet aggregation was obtained at a 5-fold final concentration of both inducers. After pretreatment of ECs with 1 mmol ASA over 30 min. the antiaggregatory effect of SIN 1 decreased, but was more pronounced (50%) than in uncovered cuvettes (25%).

Cells, Cultured↗
PubMed1991

[Objective assessment of the risk of edema in patients with venous diseases and healthy vein probands using optoelectronic volumetry].

The optoelectronic volumetry is a simple, good reproducable and effective method for measuring leg oedemas in patients with chronic venous insufficiency (CVI). Even in persons without CVI there is a significant increase of lower leg volume from the morning to the afternoon with mean increase of 51.1 ml (1.63%). These increases were not sex related, a five minutes rest played no significant part in volume increase. In patients with chronic venous insufficiency the volume increase from morning to the afternoon is very much higher (158 ml +/- 54 ml = 4.5 +/- 1.5%). Three days measurements showed an intraindividual variation of volume increase of about 20 ml (0.6% of the absolute leg volume).

Circadian Rhythm↗
PubMed1990

Platelet membrane defects in fawn hooded bleeder rats.

An inbred strain of fawn hooded rats with a congenital platelet defect shows a marked bleeding tendency with prolonged bleeding time. This haemorrhagic disorder has been exclusively related to a deficiency of nucleotides in platelet dense granules. When tested in cell electrophoresis platelets from fawn hooded bleeder rats showed a significantly lower electrophoretic mobility than normal rat platelets. Subsequent studies on the platelet membrane protein pattern by high resolution two-dimensional gel electrophoresis revealed the deficiency of a membrane glycoprotein (apparent molecular mass 90.000, isoelectric point 5.6), which is detectable in normal rat platelets after surface labeling by periodate-tritiated sodium borohydride. It seems likely, that this glycoprotein defect contributes at least partially to the disorder of platelet function in fawn hooded bleeder rats.

Animals↗
PubMed1990

Inhibition of coagulation and platelet adhesion to extracellular matrix by unfractionated heparin and a low molecular weight heparin.

In 7 healthy volunteers, the effect of a single i.v. injection of 52 mg (7,500 IU) of an unfractionated heparin (UFH) and of 52.5 mg (5,000 anti XaU) of a low molecular weight heparin (LMWH) on coagulation parameters and platelet function has been studied. Thrombin-induced platelet aggregation was inhibited after the injection of both heparins. There was no significant change of ADP or collagen-induced aggregation after LMWH of UFH. Platelet adhesion to bovine extracellular matrix was not inhibited by UFH but was significantly reduced after addition in vitro and ex vivo after administration of LMWH. Further investigation should establish the time course of LMWH effects on platelet adhesion. A long duration of this effect could be partially correlated with the antithrombotic effects of LMWH.

Adult↗
PubMed1990

Anticoagulant and antithrombotic effects of chemically modified heparins and pentosanpolysulfate.

Pig mucosal heparin (GAG 98), in which the binding site for antithrombin had been inactivated by periodate oxidation (GAG 262), a supersulfated low-molecular-weight heparin (GAG 869), a low-molecular-weight heparin (Fragmin), and sodium pentosanpolysulfate have been investigated on their anticoagulant effects in vitro and ex vivo and in an animal thrombosis model in which rat mesenteric venules are damaged by defined laser energy. GAG 262 and pentosanpolysulfate had a markedly reduced anticoagulant effect compared to heparin, Fragmin, and the supersulfated low-molecular-weight heparin fragment. Similarily, the doses necessary to inhibit thrombus formation in the laser model were much higher for GAG 262 and for pentosanpolysulfate compared to heparin and the low-molecular-weight heparin Fragmin, but much lower for the supersulfated heparin fragment. The antithrombotic effect of the low-molecular-weight heparin Fragmin and the supersulfated heparin fragment after subcutaneous injection lasted much longer than the ex vivo detectable anticoagulant effect. Although some correlation between the antithrombotic and the anticoagulant effect in the laser model is evident, there seems to be no direct correlation between amount and duration of factor IIa or factor Xa inhibition and extent and duration of the inhibition of thrombus formation.

Animals↗
PubMed1989

[Prevention of thrombosis with unfractionated and low molecular weight heparin].

2 or 3 daily injections of unfractionated heparin reduce the risk of thrombosis in patients undergoing general surgery from about 39 to 4 to 5% (sodium-fibrinogen-test). In patients at high risk (hip replacement, knee operations) a thrombosis incidence of about 20% is observed even under heparin prophylaxis. The clinical incidence of venous thrombosis is reduced to less than 1% in patients undergoing general surgery. Low molecular weight heparins have been investigated in a number of clinical trials. A single daily s.c. injection of low molecular weight heparin is as effective or more effective than 2 to 3 daily s.c. injections of unfractionated heparins in the prevention of thromboses in general surgery. The bleeding risk is not reduced compared to unfractionated heparin. Most frequent side effects of heparin prophylaxis are bleeding complications followed by thrombocytopenia between 1 to 2% and the rare but dangerous "white-clot-syndrome" (less than 0.01%). Some patients with thrombocytopenia or white-clot-syndrome can be successfully treated with a low molecular weight heparin fraction.

Dose-Response Relationship, Drug↗