One important facet is the circulatory system dysfunction, which includes capillary bed plugging. This review addresses the mechanisms of capillary plugging and highlights our recent discoveries on the roles of NO, ROS, and activated coagulation in platelet adhesion

and blood flow stoppage in septic mouse capillaries. We show that sepsis increases platelet adhesion, fibrin deposition and flow stoppage in capillaries, MK-8669 molecular weight and that NADPH oxidase-derived ROS, rather than NO, play a detrimental role in this adhesion/stoppage. P-selectin and activated coagulation are required for adhesion/stoppage. Further, platelet adhesion in capillaries (i) strongly predicts capillary flow stoppage, and (ii) may explain why severe sepsis is associated with a drop in platelet count in systemic blood. Significantly, we also show that a single bolus of the antioxidant ascorbate (injected intravenously at clinically relevant dose of 10 mg/kg) inhibits adhesion/stoppage. Our data suggest that eNOS-derived NO at the platelet-endothelial interface is anti-adhesive and required find more for the inhibitory

effect of ascorbate. Because of the critical role of ROS in capillary plugging, ascorbate bolus administration may be beneficial to septic patients whose survival depends on restoring microvascular perfusion. “
“Please cite this paper as: Wijnstok N, Hoekstra T, Eringa E, Smulders Y, Twisk J, Serne E. The relationship of body fatness and body fat distribution with microvascular recruitment: The Amsterdam Growth and Health Longitudinal Study. Microcirculation 19: 273–279, 2012. Introduction:  Microvascular function has been proposed to link body fatness to CVD and DM2. Current knowledge of these relationships is mainly based on studies in selected populations of extreme phenotypes. Whether these findings can be translated to the general population remains to be investigated. Aim:  To assess the relationship of body fatness and body fat distribution with microvascular function in a healthy population-based cohort. Methods:  Body fatness parameters were obtained by anthropometry and whole-body dual-X-ray absorptiometry (DEXA) in 2000 and 2006. Microvascular

recruitment (i.e., absolute increase in perfused capillaries after arterial occlusion, using nailfold capillaroscopy) was measured in 2006. Linear regression analysis was used to examine the NADPH-cytochrome-c2 reductase relationship of (changes in) body fatness and body fat distribution with microvascular recruitment. Results:  Data were available for 259 participants (116 men). Capillary density was higher in women than in men (difference 7.3/ mm2; p < 0.05). In the total population, the relationship between total body fatness and microvascular recruitment was positive (β = 0.43; p = 0.002), whereas a central pattern of fat distribution (trunk-over-total fatness) showed a negative relationship (β = −26.2; p = 0.032) with microvascular recruitment. However, no association remained apparent after adjustment for gender.