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

Anaesthesist. 2017 May;66(5):347-352. doi: 10.1007/s00101-017-0305-5.
[Article in German]


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: Capillary leak; Endothelium; Microcirculation; Phosphodiesterase-4 inhibitor; Sepsis.

Publication types

  • Review

MeSH terms

  • Animals
  • Capillary Leak Syndrome / drug therapy*
  • Endothelium, Vascular / drug effects*
  • Humans
  • Microcirculation / drug effects*
  • Phosphodiesterase 4 Inhibitors / therapeutic use*
  • Prognosis
  • Sepsis / drug therapy*
  • Sepsis / physiopathology*
  • Vascular Diseases / drug therapy
  • Vascular Diseases / physiopathology


  • Phosphodiesterase 4 Inhibitors