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Biomedical subjects

H K Breddin

Publications and source records attributed to H K Breddin.

At least 91 records · Page 5Linked to original sources
PubMed1989

Changes of spontaneous and induced platelet aggregation in the presence of a human endothelial cell monolayer.

A new, simple method has been developed for the investigation of platelet aggregation in the presence of a cultured confluent human endothelial cell monolayer, in disk shaped rotating cuvettes, without magnetic stirring. The endothelial cells inhibited the aggregating effect of several inducers in a concentration dependent manner. At a platelet count of 5 x 10(5)/microliter in PRP e.g. the aggregating effect of 1 microgram/microliter thrombin was completely abolished. Spontaneous aggregation was also prevented by the EC-monolayer. A correlation could be established between the inhibitory effect of ECs and the number of platelets. In PRP with a platelet count of 7 x 10(-5)/microliters the inhibitory effect of the endothelial cell monolayer significantly decreased.

Adult↗
PubMed1989

[Iloprost, a stable prostacyclin derivative, in stage 4 arterial occlusive disease. A placebo-controlled multicenter study].

The effectiveness of iloprost, a prostacyclin derivative, was assessed in a placebo-controlled multicentre trial on 101 patients with chronic arterial disease, stage IV. All patients were on a basic local treatment, 53 randomly being assigned to the iloprost group, 48 to the placebo one. Both groups received identical saline infusions, one with the other without iloprost. Infusions were given on 28 consecutive days, iloprost being added at a dose of up to 2 ng/kg.min over six hours. At the end of the treatment period, 32 of 52 patients (61.5%) of the iloprost group and eight of the 47 in the placebo group (17%) had partial or complete healing of ulcers (P less than 0.05), the treatment effect persisting in both groups for a mean duration of at least one year. Iloprost was well tolerated, once individual dosages had been appropriately adjusted. Facial flushes, headache and nausea were the most common side effects. Heart rate and blood-pressure variations did not differ between the two groups.

Adult↗
PubMed1989

Antithrombotic effects of three thrombin inhibitors in a rat model of laser-induced thrombosis.

The antithrombotic effects of three thrombin inhibitors (hirudin, NAPAP and argidipine) were investigated in an experimental thrombosis model using laser lesions of rat mesenteric venules. Furthermore, their in vitro anticoagulant activity (partial thromboplastin time, thrombin time, Heptest, inhibition of factor IIa and factor Xa) in human platelet poor plasma (PPP) and their in vitro and ex vivo activities were studied in rat plasma. All three thrombin inhibitors showed significant and dose-dependent antithrombotic effects after intravenous injection, if venules were damaged, which lasted for more than 4 but less than 8 h. The anticoagulant effect observed in vitro did not differ much between human and rat PPP. The two synthetic thrombin inhibitors NAPAP and argidipine were about as effective as hirudin in vitro; however, the ex vivo effect after intravenous injection of hirudin in rats was more pronounced than that observed with the two synthetic thrombin inhibitors. The antithrombotic effect of all three thrombin inhibitors in the laser model lasted much longer than the anticoagulant activity. This fact needs further investigations in the future.

Animals↗
PubMed1989

Effect of antibiotics on laser-induced thrombus formation in rat mesenteric arterioles.

Antibiotics were tested in a thrombosis model, in which thrombi are produced in small rat mesenteric arterioles. An interference contrast system based on a Leitz Orthoplan microscope, was used to visualize thrombus formation. Vascular lesions were produced with a Coherent CR-2 supergraphite ion laser (argon laser) in arterioles of 25-35 microns diameter. Cefmenoxim, cefotaxim (i.v.) and cephalexin orally at doses of 20 and 40 mg/kg and gentamycin 10 and 20 mg/kg (i.v.) had a marked and significant antithrombotic effect. Even more effective were cefoperazon and lamoxactam 20 and 40 mg/kg (i.v.) and tobramycin 10 and 20 mg/kg (i.v.). Azlocillin, cefoxitin, mezlocillin or spectinomycin (20 mg/kg i.v.) and penicillin or piperacillin (50 mg/kg i.v.) also showed a significant antithrombotic effect, which, however, disappeared on doubling of the applied dose.

Animals↗
PubMed1989

A PAF-acether antagonist (N 48740 RP/Rhône-Poulenc) and laser-induced thrombi in rat mesenteric vessels.

N 48740 RP, a pyrrolo(1,2-c)thiazole derivative and platelet-activating factor inhibitor, was tested in a thrombosis model, in which thrombi are produced in small rat mesenteric vessels. A phase contrast system, based on a Leitz Orthoplan microscope, was used to visualize thrombus formation. Vascular lesions were produced with a Coherent CR-2 supergraphite ion laser (argon laser) in vessels of 25-35 microns diameter. The results show a dose-dependent (5-20 mg/kg i.v.) antithrombotic effect of N 48740 RP which reaches its maximum between 30 min and 2 h after the injection and slowly decreases during the following 24-48 h.

Animals↗
PubMed1988

Plasma drug and antiplatelet profiles of the original acetylsalicylic acid preparations used in the AMIS, PARIS and German-Austrian trials for secondary prevention of myocardial infarction.

In a cross-over study 6 healthy male subjects were given for 9 days the acetylsalicylic acid (ASA) preparations used in the Aspirin Myocardial Infarction Study (AMIS), Persantine-Aspirin Reinfarction Study (PARIS) and German-Austrian secondary heart attack prevention trials, exactly according to the original study protocols. Plasma concentrations of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), as well as platelet function (collagen-induced platelet aggregation; tissue extract-induced change in platelet shape) were studied repeatedly on the first day of each medication period and were again examined on the sixth and ninth days. Differences in the plasma concentrations of ASA and its metabolites were found only on the first day, probably as a result of different absorption rates. Collagen-induced platelet aggregation was more rapidly inhibited the faster the preparation was absorbed. Each ASA preparation inhibited tissue extract-induced platelet shape change from the first dose, although statistically significant inhibition was seen only with the AMIS preparation. It is concluded that differences in the antithrombotic efficiency of ASA cannot be explained by differences in the pharmacokinetic and antiplatelet profiles of the various ASA preparations tested.

Adult↗
PubMed1988

Evaluation of the biological effects of low-molecular-weight heparins.

In experiments with a laser thrombosis model in rat mesenteric venules, where laser beams induce defined injuries at the vessel endothelium, antithrombotic potency of low-molecular-weight (LMW) heparins was calculated by the number of laser injuries required to induce vessel occluding thrombi. The antithrombotic effect of various LMW heparins was measured at defined time intervals after subcutaneous application. Simultaneously, rat blood was collected and aXa and aIIa plasma levels were determined by chromogenic substrate assays. The antithrombotic effect calculated in the animal model lasted longer than 48 h after a single subcutaneous heparin injection whereas the anticoagulative effect measured as aXa or aIIa activity was measurable only within the first 6 h after subcutaneous application. LMW heparins showed an antithrombotic effect at dosages where no influence on the coagulation system could be demonstrated.

Animals↗
PubMed1988

Effect of low-molecular-weight heparins on laser-induced thrombus formation in rat mesenteric vessels.

Laser-induced thrombi have been frequently produced in rat mesenteric vessels to investigate the effect of antithrombotic drugs. We have tested low molecular heparins in comparison to unfractionated heparin. The investigations were carried out on male Wistar rats weighing 200-300 g; the animals were anesthetized with pentobarbital sodium (Nembutal) 60 mg/kg i.p. Vascular lesions were induced with a Coherent CR-2 supergraphite ion laser (argon laser) mounted on a Leitz Orthoplan microscope. An intestinal loop was spread on a self-constructed object stage, mounted on the microscope table. The laser beam was directed through the optical path of the microscope on small mesenteric vessels in the fat-free portion of the mesentery. For the evaluation of thrombus formation the number of laser injuries needed to induce a defined thrombus was used. All low-molecular-weight heparins (preparation B, Braun; BR-Z-0601, Braun; CY 216, Choay; Fragmin, Kabi; low molecular heparin, Sandoz and Org 10172, Organon) or unfractionated heparin (Liquemin; Hoffmann-La Roche) showed a significant and dose-dependent antithrombotic effect after subcutaneous injection, if venules had been damaged. The effect lasted for 48 h, partly for over 48 h. If thrombus formation was studied after intravenous injection into arterioles as well as into venules 8 h after injection, no antithrombotic effect could be demonstrated under the influence of CY 216 or unfractionated heparin.

Animals↗
PubMed1988

Application of a laser-induced endothelial injury model in the screening of antithrombotic drugs.

A method of inducing microthrombi in small rat mesenteric vessels (approximately 20 to 30 micron) has been developed to study platelet reactions and to investigate antithrombotic drugs. For microscopy, a high-power water immersion system, based on a Leitz Orthoplan microscope, was used. In sodium pentabarbital anesthetized male Wistar rats and in fawn-hooded bleeder rats vascular lesions were produced with a Coherent CR-2 ion laser (argon laser). The laser induced vascular damage, without intravascular heat precipitates, which led to the adhesion, transformation, and aggregation of platelets at the damaged vessel wall. Fibrin threads were rarely formed in these early platelet thrombi. Thrombus formation was estimated by the number of laser injuries required to induce a defined thrombus. The first steps of thrombus formation, in particular the adhesion and reversible aggregation, were significantly reduced in this model in fawn-hooded bleeder rats. A number of different drugs modified thrombus formation in this model, for instance, ASA, defibrotide, unfractionated or low molecular heparins. It is unlikely that a single mechanism is responsible for the observed antithrombotic effects of each of these drugs. The inhibition of platelet adhesion by changes of membrane glycoproteins, interference with the early activation of plasma proteins, effects on prostaglandin metabolism, inhibition of activators stemming from damaged endothelial cells, and other effects have to be considered.

Animals↗
PubMed1987

[Jellyfish poisoning].

While bathing in the Indian Ocean a 31-year-old German woman came into contact with a jelly-fish, probably of the species Chrysaora quinquecirrha. Initial signs were inflammatory cutaneous changes on the upper trunk, and both arms and feet. Over the next few days massive edematous swelling developed over the trunk, in addition to signs of arterial underperfusion in the hands and legs. Under treatment with urokinase and prostaglandin E1 the circulatory disorder in the feet completely disappeared. But the edema on the arms and hands got worse and huge bullae developed. On the assumption of a compartment syndrome a bilateral fasciotomy was performed. Wound healing proceeded normally. However, even after six months there remained extensive sensory and motor defects in both hands and arms.

Adult↗
PubMed1987

[Inhibition of the formation of platelet thrombus by molsidomine and SIN-1 in the mesenteric vessels rats].

Molsidomine and SIN-1 were tested in a thrombosis model in which thrombi are produced in small mesenteric vessels. An interference contrast system based on a Leitz Orthoplan microscope was used to visualize thrombus formation. Vascular lesions were produced with a Coherent CR-Z supergraphite ion laser (Argon laser) in vessel of 20-30 micron diameter. Molsidomine and SIN-1 i.v. at doses of 0.1 and 0.5 mg/kg had a marked and significant antithrombotic effect in arterioles and in venules. Molsidomine at doses of 0.1 and 0.5 mg/kg had no antithrombotic effect 90 min following intravenous injection.

Animals↗
PubMed1986

Haemostasiological parameters as risk factor for new arterial occlusions in diabetics.

PARD is a prospective study sponsored by the German Research Council with the aim to establish if spontaneously enhanced platelet aggregation or changes of other hemostatic variables are risk factors for new vascular occlusions in diabetic patients. 363 diabetics (aged 45-65, 232 men, 131 women) have been observed for at least 5 years. Of the 232 men, 53 were on diet, 104 on oral antidiabetic agents and 75 on insulin. Of 131 women 16 were on diet, 46 on oral antidiabetic drugs and 69 on insulin. At entry a medical history was obtained and clinical examinations and laboratory tests were performed. Hemostatic tests and clinical examinations were repeated at 3 month's intervals. The life status was followed for all patients with the exception of 2. Until December 31, 1984, 42 patients had died, 23 from cardiovascular disease and 19 from other causes. 13 patients suffered a myocardial infarction, 11 a stroke and 53 a peripheral arterial occlusion. The occurrence of new vascular occlusions was significantly higher in men with enhanced spontaneous platelet aggregation measured by PAT III. This was not the case for women. Other hemostatic parameters with some relation to cardiovascular complications, again only in men, were fibrinogen, von Willebrand factor together with some established risk factors as triglycerides and hypertension.

Aged↗