BACKGROUND Subjects with severe hypoxemic respiratory failure have shown a high mortality in previous studies. METHODS All adult ICU patients requiring mechanical ventilation from 2005 to 2010 at Mayo Clinic were screened for severe hypoxemia (Murray lung injury score of ≥ 3). Extracorporeal membrane oxygenation, prone positioning, high-frequency oscillatory ventilation (HFOV), and inhaled va...

Endothelium-dependent vasodilation is thought to be mediated primarily by the NO/cGMP signaling pathway whereas cAMP-elevating vasodilators are considered to act independent of the endothelial cell layer. However, recent functional data suggest that cAMP-elevating vasodilators such as beta-receptor agonists, adenosine or forskolin may also be endothelium-dependent. Here we used functional and b...

In sickle cell disease, nitric oxide (NO) depletion by cell-free plasma hemoglobin and/or oxygen radicals is associated with arginine deficiency, impaired NO bioavailability, and chronic oxidative stress. In transgenic-knockout sickle (BERK) mice that express exclusively human alpha- and beta(S)-globins, reduced NO bioavailability is associated with induction of non-NO vasodilator enzyme, cyclo...

The wall shear stress (WSS) of flowing blood and the circumferential strain (CS) driven by the pressure pulse interact to impose a dynamic force pattern on endothelial cells (ECs) which can be characterized by the temporal phase angle between WSS and CS, a quantity which varies significantly throughout the circulation. To study the interaction of WSS and CS on endothelial production of vasodila...