Abstract：
Hemorrhagic shock and subsequent resuscitation can cause significant dysregulation of critical systems, including the vascular endothelium. Following hemorrhage, the endothelial lining (glycocalyx) can shed, causing release of glycocalyx components, endothelial activation, and systemic inflammation. A canine model of hemorrhagic shock was used to evaluate five resuscitation fluids, including Lactated Ringers+Hetastarch, Whole Blood (WB), Fresh Frozen Plasma+packed Red Blood Cells (FFP+pRBC), and two hemoglobin-based oxygen carrier (HBOC) fluids, for their impact on glycocalyx shedding. Under anesthesia, purpose-bred adult canines were instrumented and subjected to a controlled hemorrhage with blood being drawn until a mean arterial pressure of <50 mmHg was reached or 40 % of the estimated blood volume was removed. Canines were left in shock for 45 mins before being resuscitated with one of the resuscitation fluids over 30 mins. Following resuscitation, the dogs were monitored up to 2 weeks. Following an additional 3-4 weeks for washout, the canines repeated the protocol, undergoing each resuscitation fluid individually. Blood samples were collected during each round at various timepoints for serum isolation, which was used for detection of glycocalyx biomarker. Comparison of baseline and post-hemorrhage alone showed a significant reduction in serum protein (p<0.0001), heparan sulfate (p<0.001), and syndecan-1 (p<0.0001) concentrations, and a significant increase in hyaluronan (p<0.0001) concentration. Intercomparisons of resuscitation fluids indicated minimal differences in glycocalyx markers over time. Comparisons within each fluid showed dynamic responses in glycocalyx biomarkers over time. Relative to individual baselines, syndecan-1 was significantly reduced after resuscitation in most cases (p<0.0001), excluding WB and FFP+pRBC. In all cases, VE-cadherin was significantly elevated at 24 hr compared to baseline (p<0.001). Hyaluronan was significantly elevated by 3 hr in all cases (p<0.01), except for HBOC fluids. Total glycosaminoglycans were significantly reduced only at 3 hr (p<0.001) for non-HBOC fluids. Similarly, heparan sulfate was significantly reduced with all fluids between resuscitation and 24 hr (p<0.01), except WB. The temporal changes in canine glycocalyx biomarkers were atypical of hemorrhage response in other species. This suggests that the hemorrhage lacked severity and/or typical glycocalyx biomarkers do not reflect the canine endothelium compared to other species. Further research is needed to characterize the canine endothelium and the response to resuscitation fluids.
摘要：
失血性休克和随后的复苏可导致关键系统严重失调，包括血管内皮.出血后，内皮衬里（糖萼）可以脱落，导致糖萼成分的释放，内皮激活，和全身性炎症。犬失血性休克模型用于评估五种复苏液，包括泌乳Ringers+Hetastarch,全血（WB），新鲜冷冻血浆+包装红细胞（FFP+pRBC），和两种基于血红蛋白的氧载体（HBOC）液，它们对糖萼脱落的影响。在麻醉下,对目的饲养的成年犬进行测量,并进行控制出血,抽血直至平均动脉压<50mmHg或排除40%的估计血容量.犬科动物在休克中放置45分钟,然后用其中一种复苏液复苏超过30分钟。复苏后,对狗进行了长达2周的监测。再冲洗3-4周后，犬科动物重复了协议，分别接受每种复苏液。在每个循环期间在不同时间点收集血样用于血清分离。用于检测糖萼生物标志物。基线和单独出血后的比较显示血清蛋白显着降低（p<0.0001），硫酸乙酰肝素（p<0.001），和syndecan-1(p<0.0001)浓度，透明质酸浓度显著增加(p<0.0001)。复苏液的相互比较表明，随着时间的推移，糖萼标记物的差异很小。每种流体内的比较显示糖萼生物标志物随时间的动态响应。相对于单个基线，在大多数情况下，syndecan-1在复苏后显著降低(p<0.0001)，不包括WB和FFP+pRBC。在所有情况下,与基线相比,VE-钙黏着蛋白在24小时显著升高(p<0.001)。在所有情况下，透明质酸在3小时内显着升高（p<0.01），除了HBOC液体。对于非HBOC流体,总糖胺聚糖仅在3小时时显著减少(p<0.001)。同样，硫酸乙酰肝素在复苏和24小时之间的所有液体显着减少（p<0.01），除了WB。在其他物种中，犬糖萼生物标志物的时间变化与出血反应不典型。这表明与其他物种相比，缺乏严重程度的出血和/或典型的糖萼生物标志物不能反映犬内皮。需要进一步的研究来表征犬内皮和对复苏液的反应。
