Effects of enalapril on disseminated intravascular thrombin formation during systemic inflammation

Marsik, Claudia; Graninger, Marianne; Mackman, Nigel; Østerud, Bjarne; Luther, Thomas; Jilma, Bernd

doi:10.1016/s0008-6363(03)00363-8

Cited by 2 publications

(1 citation statement)

References 30 publications

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“…Thus, the lack of in vivo effects in our trial could indicate that only higher concentrations of NO donors may reduce TF gene expression. Another reason may be the differential behavior of isolated monocytes and monocytes in whole blood, which has been demonstrated for different physiological mediators [50,51].…”

Section: Discussionmentioning

confidence: 99%

Effects of aspirin and NO-aspirin (NCX 4016) on platelet function and coagulation in human endotoxemia

Derhaschnig

Schweeger-Exeli²,

Marsik³

et al. 2010

Platelets

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Acetylsalicylic acid (ASA) prevents thromboembolic events by inhibiting platelet function through blocking of cyclooxygenase type 1 (COX-1). A nitroderivate of ASA, 2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)-phenyl ester (NCX 4016) was synthesized, which additionally acts through nitric oxide release. In various in vitro and animal studies NCX 4016 exhibited antithrombotic and anti-platelet properties. We used the standardized model of endotoxin infusion into human volunteers to compare the effects of NCX 4016 and ASA on platelet function and TF-induced coagulation activation. The trial consisted of two parts. In the first part, 10 healthy male volunteers were included in a randomized, open cross-over trial to find a NCX formulation with optimal tolerability and pharmacokinetic data were obtained. The second part was a randomized, double blind placebo controlled clinical trial consisting of 30 healthy male volunteers in three parallel groups (n = 10 per group). Volunteers received either NCX 4016 (800 mg b.i.d.), ASA (425 mg b.i.d.) or placebo for 7 days, before infusion of 2 ng/kg endotoxin on day 8. ASA attenuated the endotoxin-induced platelet plug formation (measured by PFA-100) significantly better than NCX 4016 and placebo (p < 0.004), while there was no difference in soluble P-selectin or VWF-levels. Urine 11-dehydro-thromboxane B(2) levels were significantly lower in the ASA and NCX 4016 groups as compared to placebo (p < 0.05). Neither ASA nor NCX 4016 significantly changed prothrombin fragment(1 + 2), D-Dimer or tissue factor (TF)-mRNA levels. In summary, NCX 4016 had no effect on VWF release, platelet activation as measured by soluble P-selectin or TF gene expression. NCX 4016, at the dose tested, unlike ASA, had no effect on platelet collagen/epinephrine induced plug formation under high shear rates.

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Section: Discussionmentioning

confidence: 99%