Der Anaesthesist

, Volume 66, Issue 5, pp 347–352 | Cite as

Phosphodiesterase-4-Inhibition zur Therapie der endothelialen Schranken- und Mikrozirkulationsstörung in der Sepsis

Intensivmedizin
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Zusammenfassung

Die Sepsis wird typischerweise durch eine Störung der endothelialen Barrierefunktion („capillary leak“) und eine Mikrozirkulationsstörung begleitet. Diese münden in ein Organversagen. Da es sich bei diesen Ereignissen um entscheidende und prognosebestimmende Vorgänge bei septischen Entzündungsprozessen handelt, wäre die spezifische Therapie sowohl der endothelialen Schrankenstörung als auch der Mikrozirkulationsstörung von größter Bedeutung. Zahlreiche Arbeiten aus der Grundlagenforschung haben in den letzten Jahren erheblich zum verbesserten Verständnis der Pathophysiologie dieser Prozesse beigetragen. Ein vielversprechender therapeutischer Ansatz zur Verbesserung der endothelialen Schrankenstörung und der Mikrozirkulationsstörungen scheint die Modulation der verminderten Aktivität der Rho-GTPase Rac1 durch Stabilisierung intraendothelialer cAMP-Spiegel (zyklisches Adenosinmonophosphat), z. B. durch Applikation von Phosphodiesterase-4-Hemmern, zu sein. Die bisherigen tierexperimentellen Ansätze und die Erkenntnisse über die zellulären Mechanismen der letzten Jahre sollen hier vorgestellt und diskutiert werden.

Schlüsselwörter

Sepsis Endotheliale Schrankenstörung Endothel Mikrozirkulation Phosphodiesterase-4-Inhibitor 

Phosphodiesterase 4 inhibition for treatment of endothelial barrier and microcirculation disorders in sepsis

Abstract

Sepsis is commonly associated with loss of microvascular endothelial barrier function (capillary leak) and dysfunctional microcirculation, which both promote organ failure. The development of a distinct therapy of impaired endothelial barrier function and disturbed microcirculation is highly relevant because both of these phenomena constitute crucial processes which critically influence the prognosis of patients. Numerous in vivo and in vitro trials over the past years have fostered a better understanding of the pathophysiology of capillary leak. Furthermore, promising data in animal models show that therapeutic modulation of endothelial barrier function and microcirculation can be achieved by stabilizing endothelial cAMP (cyclic adenosine monophosphate) levels followed by activation of Rho-GTPase Rac1, e. g. by phosphodiesterase 4 inhibitors. This review summarizes and discusses recent findings of cellular mechanisms and in vivo trials.

Keywords

Sepsis Capillary leak Endothelium Microcirculation Phosphodiesterase-4 inhibitor 
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Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

J. Wollborn, N. Schlegel und M.A. Schick geben an, dass kein Interessenkonflikt besteht.

Alle nationalen Richtlinien zur Haltung und zum Umgang mit Labortieren wurden eingehalten und die notwendigen Zustimmungen der zuständigen Behörden liegen vor.

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Copyright information

© Springer Medizin Verlag GmbH 2017

Authors and Affiliations

  1. 1.Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Freiburg, Medizinische FakultätAlbert-Ludwigs-Universität FreiburgFreiburgDeutschland
  2. 2.Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und KinderchirurgieUniversitätsklinikum WürzburgWürzburgDeutschland

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