Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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The purpose of the study was to investigate microcirculation and vascular reactivity during experimental endotoxemia and endotoxin tolerance in humans by comparing different methods of approach. Endotoxin tolerance was induced in nine healthy volunteers by intravenous injection of 2 ng . kg(-1) . d(-1) LPS for 5 consecutive days. Microcirculation and vascular reactivity were monitored before and after LPS administrations on days 1 and 5 by near-infrared spectroscopy, sidestream dark-field imaging, and forearm blood flow by venous occlusion strain-gauge plethysmography during local intra-arterial infusion of endothelial-dependent vasodilator acetylcholine (0.5, 2, and 8 microg . min(-1) . dL(-1)). ⋯ Sidestream dark-field imaging showed 33% (IQR, 14%-40%) and 30% (IQR, 10%-33%) diminished flow in medium and large microvessels, respectively, 2 h after LPS administration on day 1 (P = 0.07 and 0.04, respectively), which was absent on day 5 (P = 0.47 for both vessels). Forearm blood flow measurements showed an attenuation of acetylcholine-induced vasodilatory response, with 67% (IQR, 45%-72%) 4 h after the first LPS administration (P = 0.01), but not when tolerance was present on day 5 (P = 0.61). Human endotoxemia results in endothelial dysfunction that can be adequately detected with different methods and was restored with development of LPS tolerance.
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Microvascular responses to blood volume restitution using red blood cells (RBCs) with modified hemoglobin (Hb) oxygen affinity were studied in the hamster window chamber model during resuscitation from hemorrhagic shock. Allosteric effectors inositol hexaphosphate and 5-hydroxymethyl-2-furfural were introduced into the RBCs by electroporation to decrease and increase Hb-oxygen affinity. In vitro P50s (partial pressure of oxygen at 50% Hb saturation) were modified to 10 and 50 mmHg (normal P50, 32 mmHg). ⋯ There was no significant difference in oxygen extraction. Oxygen extraction ratio (oxygen extraction/oxygen delivery) x 100 was significantly higher in HP50 than in LP50. These results suggest that lowering blood P50 in resuscitation provides improved microvascular function in comparison with higher P50.