琥珀酰水杨酸交联血红蛋白改善脓毒症的氧利用研究

Diaspirin cross-linked hemoglobin improves whole body oxygen utilization in a septic model with supply dependency

目的：研究琥珀酰水杨酸交联血红蛋白（ＤＣＬＨｂ）在脓毒症时对氧利用的影响。方法：使用绵羊脓毒症模型，自身输血随机对照设计，实验分两个阶段进行：前３ 日建立动、静脉通路，采集自身全血，行盲肠结扎穿孔术（ＣＬＰ）。ＣＬＰ术后４８小时进入第二阶段，通过降低吸入氧分数（ＦｉＯ２）使动物进入氧供依赖，然后分别快速推入全血２００ ｍ ｌ或ＤＣＬＨｂ ２００ ｍ ｌ，在随后的６０ 分钟内选取不同时间点进行有关项目检测。结果：１１只动物进入ＤＣＬＨｂ 组；１０只进入全血组。复苏后，指标变化最明显时出现在第５ 分钟，ＤＣＬＨｂ 使全身氧耗（ＶＯ２ ）显著和立即增加，动脉乳酸和肠道血流量也明显增加。对照组在该点ＶＯ２ 变化不显著，而且肠道ＶＯ２、全身氧摄取（ＥＲＯ２ ）下降。１５ 分钟后，ＤＣＬＨｂ 的有效性迅速钝化。复苏后２组间血压（ＢＰ）有明显差异，ＤＣＬＨｂ 组始终高于全血组，直至研究结束。结论：在脓毒症和氧供依赖的状态下，ＤＣＬＨｂ 能够短暂但迅速和明显地提高全身氧耗；反之，全血并未显示任何有益的作用，甚至有害。ＤＣＬＨｂ 提高氧耗似乎是由于微循环和氧利用的改善，与全身流量和氧输送无关。

Objective:To evaluate the efficacy of diaspirin crosslinked hemoglobin (DCLHb) on improvement of whole body O 2 utilization in a septic ovine model of supplydependency.Methods:Prior to cecal ligation and puncture (CLP),200 ml of blood was collected from 21 sheep,and then animals were subjected to sepsis by CLP.48 hours after CLP,O 2 supple dependency,defined as a 20% reduction in O 2 consumption (O 2) from baseline,was induced by sequentially decreasing FiO 2.Sheep were then randomly assigned into treatment group (200 ml DCLHb of 10 g Hb/100 ml) and control group (200 ml of autologous whole blood).Parameters relevant to oxygen utilization were recorded prior to and after transfusion.Results:The sheep transfused with DCLHb ( n =11) demonstrated a statistically significant increase in whole body O 2 and blood pressure at 5 minutes post transfusion.Also,a significant increase of blood flow to the gut was observed at the same time point.However,the control group ( n =10) did not show any significant elevation in whole body O 2,conversely a significant decrease in gut oxygen extraction was observed after transfusion of whole blood.Nevertheless,the efficacy of DCLHb was quickly blunted at the subsequent measurements,except the blood pressure.There was no marked difference in outcome between two groups.Conclusions:DCLHb seems to be effective in improving the oxygen utilization in sepsis,which is independent on the increase of O 2 delivery.Conversely,the whole blood did not show any beneficial effect,even harmful under the given state.The beneficial effect of DCLHb on temporary increase in systemic O 2 might be associated with improvement of microcirculation and O 2 utilization,rather than systemic cardiac output and O 2 delivery.