WT/AngII mice were also treated with either tissue factor antibody, antithrombin III, heparin, hirudin, or murine APC. TF immunoblockade or hirudin treatment did not prevent the AngII-induced acceleration of thrombosis. While antithrombin III treatment prevented the acceleration in both thrombus onset and flow cessation, heparin

only improved the time for blood flow cessation. Neither selleck kinase inhibitor WT mice treated with murine APC nor EPCR-TgN were protected against AngII-induced thrombus development. A similar lack of protection was noted in PAI-1deficient mice. These findings implicate a role for thrombin generation pathway in the accelerated thrombosis induced by AngII and suggest that an impaired protein C pathway and increased PAI-1 do not JAK drugs make a significant contribution to this model of microvascular thrombosis. “
“Please cite this paper as: Frantz, Engelberger, Liaudet, Mazzolai, Waeber and Feihl (2012). Desensitization of Thermal Hyperemia in the Skin is Reproducible. Microcirculation 19(1), 78–85. Objective:  Local heating increases skin blood flow SkBF (thermal hyperemia). In a previous study, we reported that a first local thermal stimulus could attenuate

the hyperemic response to a second one applied later on the same skin spot, a phenomenon that we termed desensitization. However, other studies found no evidence for desensitization in similar conditions. The aim of the present work was to test whether it was related to differences in instrumentation. Methods:  Twenty-eight healthy young males were studied. Two pairs of heating chambers, one custom-made (our study) and one commercial (other groups), were affixed to forearm skin. SkBF was measured with single-point laser-Doppler flowmetry (LDF) (780 nm) in one pair, and

laser-Doppler imaging (LDI) (633 nm) in the other. A temperature step from 34 to 41°C, was applied for 30 minutes and repeated after two hours. Results:  During the NADPH-cytochrome-c2 reductase second thermal challenge, the plateau SkBF was lower than during the first thermal and was observed with each of the four combinations of SkBF measurement techniques and heating equipment (p < 0.05 for all conditions, range −9% to −16% of the initial value). Conclusion:  Desensitization of thermal hyperemia is not specific to peculiar operating conditions. In nonglabrous human skin, a local rise in temperature is a powerful stimulus for local vasodilation, mediated by neurogenic reflexes and locally released substances [12,13,15,16]. The mechanisms implicated in this so-called thermal hyperemia remain incompletely defined. In contrast with thermoregulatory skin vasodilation, it is not mediated by central reflexes because it is unaffected by regional nerve block [17] and is preserved in grafted skin [5].