Microvascular research
-
Microvascular research · Mar 2010
Validation of near-infrared laser speckle imaging for assessing microvascular (re)perfusion.
The present study was conducted to compare laser speckle imaging (LSI) with sidestream dark field (SDF) imaging (i.e., capillary microscopy) so as to validate the use of LSI for assessing microvascular (re)perfusion. For this purpose, LSI and SDF measurements were performed on the human nail fold during gradual occlusion of the upperarm circulation to modify nail fold perfusion under controlled circumstances. Additionally, a vascular occlusion test was performed to test the ability of LSI to detect rapid changes in tissue perfusion during reactive hyperemia and a hyperthermic challenge was performed to measure LSI perfusion at maximum functional capillary density. ⋯ The main finding was that changes in perfusion as measured by LSI correlated well with changes in capillary red blood cell velocities as measured by SDF imaging during controlled reduction of the (micro)vascular perfusion. It was further shown that LSI is capable of measuring tissue perfusion at high temporal and spatial resolution. In conclusion, LSI can be employed to accurately quantitate microvascular reactivity following ischemic and hyperthermic challenges.
-
Microvascular research · Mar 2010
Rac GTPase is a hub for protein kinase A and Epac signaling in endothelial barrier protection by cAMP.
Elevation in intracellular cAMP level has been associated with increased endothelial barrier integrity and linked to the activation of protein kinase A (PKA). Recent studies have shown a novel mechanism of cAMP-mediated endothelial barrier regulation via cAMP-dependent nucleotide exchange factor Epac1 and Rap1 GTPase. This study examined a contribution of PKA-dependent and PKA-independent pathways in the human pulmonary endothelial (EC) barrier protection by cAMP. ⋯ SiRNA-induced Rac knockdown suppressed barrier protective effects of both PKA and Epac signaling in pulmonary EC. Intravenous administration of either 6Bnz, or 8CPT, significantly reduced lung vascular leak in the murine model of lung injury induced by high tidal volume mechanical ventilation (HTV, 30 ml/kg, 4 h), whereas combined treatment with 6Bnz and 8CPT showed no further additive effects. This study dissected for the first time PKA and Epac pathways of lung EC barrier protection caused by cAMP elevation and identified Rac GTPase as a hub for PKA and Epac signaling leading to enhancement of lung vascular barrier.