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  • 1
    ISSN: 1432-1440
    Keywords: Nisoldipine ; Thromboxane B2 ; 6-Oxo-prostaglandin F1α ; Platelet aggregation ; Blood pressure ; Placebo-controlled study ; Human volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of the calcium antagonist nisoldipine on collagen-induced platelet aggregation and platelet thromboxane formation was studied ex vivo in healthy male volunteers in a double-blind, placebo-controlled crossover design. Measurements of general haemodynamics, immunoreactive 6-oxo-prostaglandin F1α and thromboxane B2 ex vivo and collagen-induced (0.6 and 2.5 µg/ml) platelet aggregation were performed immediately before (time 0), 0.5 h, 1 h and 2 h after ingestion of 10 mg nisoldipine or an identical placebo tablet. Compared with the control response at time 0, administration of nisoldipine resulted in a significant inhibition of both low-collagen-induced platelet aggregation and formation of immunoreactive thromboxane B2 at time 0.5 h. There were no changes in heart rate or systolic blood pressure but a significant decrease in diastolic blood pressure by nisoldipine at 1 h. No such change was obtained with placebo and there were also no alterations with nisoldipine in platelet aggregation and thromboxane formation after stimulation by high-dose collagen at this or any other time of the study. The data demonstrate a platelet-in-hibitory potential of nisoldipine in healthy men which is probably related to an increased resistance of the platelet membrane against foreign stimuli.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 64 (1986), S. 545-551 
    ISSN: 1432-1440
    Keywords: Iloprost ; Antiplatelet actions ; Blood pressure ; Regional perfusion ; Peripheral arterial obliterative disease (PAOD) ; Dose-response study ; Controlled trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II–III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg×min for 4 h, with an interval of 2–3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5–2.0 ng/kg×min iloprost, indicating that iloprost reduced platelet stimulation by 50%–70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg × min. It is concluded that iloprost administered i.v. at doses of 1–2 ng/kg×min in patients with stage II–III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 316 (1981), S. 252-255 
    ISSN: 1432-1912
    Keywords: Carbacyclin-Derivative ; Prostacyclin ; ZK 36 374 ; Vessel tone ; Platelet aggregation ; Platelet disaggregation ex vivo ; Blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The vascular and antiplatelet activities of a new, chemically stable carbacyclin derivative (ZK 36 374) were investigated and compared to PGI2. ZK 36 374 dose-dependently relaxed bovine coronary artery strips in vitro but was without direct effects on strips of bovine coronary veins which were contracted by PGI2. ZK 36 374 dose-dependently inhibited the ADP-, thrombin- and collagen-induced platelet aggregation in human platelet-rich plasma and disperded preformed platelet aggregates in whole blood of cats ex vivo. The IC50 was 0.2–1.1 (antigaggregation) and 13 (disaggregation) nM, respectively, and in the same range as PGI2. The maximum antiplatelet dose of ZK 36 374 (resolution of platelet aggregates) in anaesthetized cats in vivo was 0.45 nmoles/kg x min, and could be increased up to 3 nmoles/kg x min, i.e. 6–7-fold without significant changes in arterial blood pressure and heart rate. This indicates an appreciable dissociation between antiplatelet and blood pressure-lowering activities of this compound, at least in this model. It is concluded that ZK 36 374 is the first, chemically stable prostacyclin-mimetic agent that is equipotent to PGI2 in vitro and might be superior to PGI2 in vivo because of a reduced blood pressure-lowering activity.
    Type of Medium: Electronic Resource
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