RESUMO
OBJECTIVES: Recombinant activated factor VII (rFVIIa) is increasingly being given to treat massive bleeding. However, there is no clear guidance on which patients are suitable for treatment and how the effects of treatment should be monitored. The aim of this in vitro study was to assess the coagulation status of severely hemodiluted blood samples before and after treatment with therapeutic doses of rFVIIa and/or fibrinogen with 2 viscoelastic point-of-care coagulation analyzers: ROTEM (Pentapharm GmbH, Munich, Germany) and Sonoclot (Sienco Inc, Arvada, CO). DESIGN: Laboratory study. SETTING: Research coagulation laboratory. PARTICIPANTS: Ten healthy male volunteers without hereditary or acquired coagulation disorders. INTERVENTIONS: Blood samples were obtained. After severe hemodilution with albumin 5%, therapeutic doses of rFVIIa and/or fibrinogen were added, and the coagulation status was assessed with new 1:1,000 diluted tissue factor-activated tests from ROTEM and Sonoclot. MEASUREMENTS AND MAIN RESULTS: The administration of therapeutic doses of rFVIIa to hemodiluted samples shortened the initiation phase of coagulation only. Isolated fibrinogen administration to physiologic levels improved both the initiation of coagulation as well as clot formation and strength. Combined fibrinogen and rFVIIa administration further improved both effects. CONCLUSIONS: ROTEM and Sonoclot were able to monitor the effects of rFVIIa and fibrinogen administration with 1:1,000 diluted tissue factor-activated tests. The efficacy of rFVIIa was largely dependent on the presence of high levels of fibrinogen in reversing this severe dilutional coagulopathy.
Assuntos
Fator VIIa/uso terapêutico , Fibrinogênio/uso terapêutico , Hemodiluição/efeitos adversos , Adulto , Testes de Coagulação Sanguínea , Humanos , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: There is increasing evidence for rapid nongenomic effects of aldosterone. Therefore, we studied the immediate effects of aldosterone on vascular reactivity in rat aortic ring segments and on endothelial and vascular smooth muscle cellular responses. METHODS AND RESULTS: In endothelium-intact ring segments, aldosterone attenuated phenylephrine-mediated constriction (maximal reduction, 25+/-4% below control phenylephrine-mediated constriction). In contrast, in endothelium-denuded vessels, aldosterone mediated a monophasic dose-dependent enhancement of vasoconstrictor response. In endothelial cells, aldosterone caused a phosphatidylinositol 3-kinase (PI3K)-dependent increase in nitric oxide synthase activity as well as PI3K-dependent activation of extracellular signal-regulated kinase 1/2 and p70 S6 kinase. CONCLUSIONS: Overall, these data support a novel effect of aldosterone on vascular endothelial and smooth muscle cell function. These rapid effects of aldosterone might be important in both the short- and long-term regulation of peripheral vascular resistance. Furthermore, in the setting of endothelial dysfunction, alterations in aldosterone's short-term vascular responses might contribute to its pathophysiological effects in cardiovascular disease.