The impact of double sequential external defibrillation on termination of refractory ventricular fibrillation during out-of-hospital cardiac arrest.

Background: Despite significant advances in resuscitation efforts, there are some patients who remain in ventricular fibrillation (VF) after multiple shocks during out-of-hospital cardiac arrest (OHCA). Double sequential external defibrillation (DSED) has been proposed as a treatment option for patients in refractory VF.

Objective: We sought to explore the relationship between type of defibrillation (standard vs DSED), the number of defibrillation attempts provided and the outcomes of VF termination and return of spontaneous circulation (ROSC) for patients presenting in refractory VF.

EPAC1 promotes adaptive responses in human arterial endothelial cells subjected to low levels of laminar fluid shear stress: Implications in flow-related endothelial dysfunction.

Blood flow-associated fluid shear stress (FSS) dynamically regulates the endothelium's ability to control arterial structure and function. While arterial endothelial cells (AEC) subjected to high levels of laminar FSS express a phenotype resistant to vascular insults, those exposed to low levels of laminar FSS, or to the FSS associated with oscillatory blood flow, are less resilient. Despite numerous reports highlighting how the cAMP-signaling system controls proliferation, migration and permeability of human AECs (HAECs), its role in coordinating HAEC responses to FSS has received scant attention.

Adaptive phenotypic modulation of human arterial endothelial cells to fluid shear stress-encoded signals: modulation by phosphodiesterase 4D-VE-cadherin signalling.

Although cAMP-signalling regulates numerous functions of vascular endothelial cells (VECs), including their ability to impact vascular resistance in response to changes in blood flow dynamics, few of the mechanisms underlying these effects have yet to be described. In addition to forming stable adherens junctions (AJs) in static VEC cultures, VE-cadherin (VECAD) has emerged as a critical component in a key mechanosensor responsible for linking altered blood flow dynamics and the VEC-mediated control of vascular resistance. Previously, a cAMP phosphodiesterase, PDE4D, was shown to coordinate the VEC permeability limiting effects of cAMP-elevating agents in human arterial VECs (HAECs).

Cyclic nucleotide phosphodiesterases (PDEs): coincidence detectors acting to spatially and temporally integrate cyclic nucleotide and non-cyclic nucleotide signals.

The cyclic nucleotide second messengers cAMP and cGMP each affect virtually all cellular processes. Although these hydrophilic small molecules readily diffuse throughout cells, it is remarkable that their ability to activate their multiple intracellular effectors is spatially and temporally selective. Studies have identified a critical role for compartmentation of the enzymes which hydrolyse and metabolically inactivate these second messengers, the PDEs (cyclic nucleotide phosphodiesterases), in this specificity.