This study was designed to determine whether sepsis modifies the ability to preserve vital organ O2 delivery (QO2) across a clinically relevant range of hematocrits. Ninety rats were randomly allocated to cecal ligation and perforation (CLP) or a sham (Sham) procedure. With the use of rat plasma, rat whole blood, or packed rat red blood cells, respectively, randomization into three different hematocrit subgroups followed: low (21-28%), middle (33-40%), and high (45-52%). Organ blood flow values (Q) were measured by the radioactive microsphere technique, and organ QO2 values were calculated. Twenty-four hours after laparotomy, the hematocrit grouping had not modified the interorgan distribution of Q or QO2 in either the CLP or Sham rats. To characterize overall metabolic O2 reserve, rats were then exposed to hypoxia (inspired O2 fraction, 0.08) for 20 min. Whereas cardiac output increased significantly during hypoxia in all experimental groups, myocardial QO2 failed to increase in the low hematocrit Sham subgroup and fell significantly in both the middle- and low-hematocrit CLP subgroups. There was also a lesser redistribution of QO2 away from the small intestine in the low-hematocrit compared with the high-hematocrit CLP subgroup. We conclude that myocardial QO2 is more effectively maintained in septic hypoxic rats if the hematocrit is maintained at levels >45%.
Mechanisms of sepsis‐associated encephalopathy (SAE) are largely un‐investigated, however, impaired function of cerebrovascular endothelium has been suggested to play a key role. Our recent findings indicate that Severe Sepsis in humans results in up‐regulation of 13 out of 42 pro‐inflammatory cytokines/chemokines analyzed in blood plasma (e.g. IL‐6, MCP‐1, MIP‐1, IL‐8, IP‐10).In this study we used immortalized human‐derived cerebrovascular endothelial cells (hCVEC) to assess activation/dysfunction of hCVEC in response to stimulation with plasma (20% vol/vol) obtained from either patients with Severe Sepsis (hSSP) or healthy controls. Stimulation of hCVEC with hSSP for 1hr resulted in hCVEC activation as evidenced by increased ROS production (DHR123 oxidation). Subsequently, stimulation of hCVEC with hSSP resulted in increased PMN adhesion to hCVEC under conditions of flow (shear stress 1dyn/cm2) and increased hCVEC permeability as assessed by decreased transendothelial electric resistance. Interestingly, hSSP failed to induce activation of inflammation‐relevant transcription factor, NF‐κB (ELISA) following 1hr stimulation.In summary, our data indicate that pro‐inflammatory substance(s) present in human Severe Sepsis plasma induce activation/dysfunction of cerebrovascular endothelial cells, thus may contribute to the development of SAE (IRF 08‐10)
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