摘要目的 观察血红蛋白氧载体(HBOC)对非控制性失血性休克大鼠的早期复苏效果.方法 将170只SD大鼠按随机数字表法分为乳酸林格液(LR)对照组、全血对照组及0.5％、2.0％、5.0％ HBOC组,每组34只.采用离断脾动脉方法使平均动脉压(MAP)降至40 mmHg(1 mmHg=0.133 kPa)制备非控制性失血性休克大鼠模型.各组分别于制模成功后输注相应液体,维持MAP在50 mmHg 1 h,然后结扎脾动脉彻底止血,再次输注液体,维持MAP 70 mmHg和80 mmHg各1h,在维持MAP 80 mmHg输注液体完毕后,均用LR补充至2倍失血量,再继续观察2h.各组分别取16只大鼠用于观察存活率和失血率;再取10只大鼠用于测定血流动力学指标[MAP、左室收缩压(LVSP)和左室压力上升最大速率(+dp/dt max)];另外8只大鼠用于测定心排血量(CO)和组织氧供(DO2).结果 ①单纯采用LR复苏时,动物失血率高达60％ ～ 70％.与LR对照组比较,全血复苏可显著降低非控制性失血性休克大鼠止血前失血率[(46.6±4.5)％比(62.3±4.0)％,P＜0.01];0.5％、2.0％、5.0％ HBOC复苏也可显著降低失血率,以5.0％ HBOC组降低更为显著,与LR对照组比较差异有统计学意义[(45.6±4.1)％比(62.3±4.0)％,P＜0.01].②单纯采用LR复苏时,大鼠死亡较快,存活时间短,12 h仅存活1只,没有大鼠存活超过24 h.与LR对照组比较,全血复苏可提高非控制性失血性休克大鼠存活率,且存活时间明显延长(h:20.4±4.6比3.5±1.1,P＜0.01);0.5％、2.0％、5.0％ HBOC也可显著延长大鼠存活时间,以5.0％HBOC组效果最好,24 h存活4只,存活时间较LR对照组明显延长(h:18.4±4.0比3.5±1.1,P＜O.01),且与全血对照组相当.③与休克前比较,非控制性失血性休克大鼠CO、DO2和血流动力学指标均显著降低;随补液时间延长,各组上述指标均逐渐升高.与LR对照组比较,全血复苏可明显提高非控制性失血性休克大鼠各时间点CO、DO2,改善血流动力学;3个浓度HBOC也可提高止血后维持MAP 80 mmHg 1 h及复苏后1h、2h大鼠的CO、DO2和血流动力学指标,以5.0％ HBOC组效果更加显著,与LR对照组比较差异有统计学意义[CO(×10-3,L/min):维持MAP 80 mmHg 1 h为72.84±2.84比63.11±2.38,复苏后1h为70.25±4.55比59.88±9.31,复苏后2h为71.51±2.90比53.24±6.32;DO2 (L·min-1·m-2):维持MAP 80 mmHg 1 h为271.9±13.5比159.1±25.4,复苏后1h为261.0±15.0比145.7±20.1,复苏后2h为249.6±12.0比107.4±18.2;MAP (mmHg):维持MAP80 mmHg 1 h为82.1±2.1比74.0±2.8,复苏后1h为107.5±9.3比64.0±5.7,复苏后2h为104.0±9.7比73.0±4.2;LVSP (mmHg):维持MAP 80 mmHg 1 h为128.6±7.9比103.8±0.8,复苏后1h为129.3±15.0比99.4±0.0,复苏后2h为127.5±11.3比97.4±0.0;+dp/dt max(mmHg/s):维持MAP 80 mmHg 1 h为6534.2±787.6比5 074.0±71.7,复苏后1h为5961.5±545.4比4934.5±510.2,复苏后2h为5 897.4±350.5比4534.7±489.2,均P＜0.05].结论 创伤失血性休克早期应用HBOC能明显延长大鼠的存活时间,提高存活率,改善血流动力学、心脏功能和组织氧供应,并呈剂量依赖性,5.0％ HBOC的复苏效果与全血相当.

abstractsObjective To investigate the early resuscitation effect of hemoglobin-based oxygen carriers (HBOC) in rats with uncontrolled hemorrhagic shock.Methods 170 Sprague-Dawley (SD) rats were randomly divided into five groups:lactate Ringer solution (LR) control group,whole blood control group,and 0.5％,2.0％,5.0％ HBOC groups,with 34 rats in each group.The uncontrolled hemorrhagic shock model in SD rats was reproduced by cutting off the splenic artery branch,and induced mean arterial pressure (MAP) reducing to 40 mmHg (1 mmHg =0.133 kPa).The corresponding solution was infused after model reproduction in each group,maintaining MAP at 50 mmHg for 1 hour,then completely ligating and hemostasis,and maintaining MAP at 70 mmHg for 1 hour and 80 mmHg for 1 hour respectively,after maintaining MAP 80 mmHg,all were supplemented with LR to 2 times blood loss volume.The survival rate and blood loss rate were observed in 16 rats in each group,hemodynamics parameters including MAP,left ventricular systolic pressure (LVSP) and the maximum rate of left ventricular pressure rise (+dp/dtmax) were determined in another 10 rats,and cardiac output (CO) and tissue oxygen supply (DO2) were observed in the rest 8 rats.Results ① When resuscitation by LR alone,the blood loss rate of animals was as high as 60％ to 70％.Compared with the LR control group,whole blood recovery could significantly reduce the blood loss rate before hemostasis in uncontrolled hemorrhagic shock rats [(46.6 ± 4.5)％ vs.(62.3 ± 4.0)％,P ＜ 0.01];0.5％,2.0％,5.0％ HBOC could significantly decrease the blood loss rate,especially in 5.0％ HBOC group with significant difference as compared with that in the LR control group [(45.6±4.1)％ vs.(62.3±4.0)％,P ＜ 0.01].② When LR was used alone for resuscitation,the rats died quickly and survived for a short time.Only one rat survived for 12 hours,and no rat survived for more than 24 hours.Compared with the LR control group,whole blood resuscitation could improve the survival rate of uncontrolled hemorrhagic shock rats,and the survival time was significantly prolonged (hours:20.4± 4.6 vs.3.5 ± 1.1,P ＜ 0.01);0.5％,2.0％ and 5.0％ HBOC also significantly prolonged the survival time of rats.The 5.0％ HBOC group had the best effect,4 rats survived in 24 hours,and the survival time was significantly longer than that of the LR control group (hours:18.4 ± 4.0 vs.3.5 ± 1.1,P ＜ 0.01),and it was the same as the whole blood control group.③ Compared with pre-shock,CO,DO2 and hemodynamic parameters of uncontrolled hemorrhagic shock rats were significantly decreased,and the above parameters were gradually increased with the prolongation of rehydration time.Compared with the LR control group,whole blood resuscitation could significantly increase CO and DO2,and improve hemodynamics in rats with uncontrolled hemorrhagic shock at different time points.Three concentrations of HBOC could also increase CO,DO2 and other hemodynamic parameters of rats at 1 hour of maintaining MAP of 80 mmHg after hemostasis and 1 hour and 2 hours after resuscitation.The effect of 5.0％ HBOC group was more significant than that of the LR control group with statistically significant difference [CO (× 10-3,L/min):72.84±2.84 vs.63.11±2.38 at 1 hour of maintaining MAP of 80 mmHg,70.25±4.55 vs.59.88 ± 9.31 at 1 hour after resuscitation,71.51 ± 2.90 vs.53.24 ± 6.32 at 2 hours after resuscitation;DO2 (L· min-1 · m-2):271.9± 13.5 vs.159.1 ±25.4 at 1 hour of maintaining MAP of 80 mmHg,261.0± 15.0 vs.145.7±20.1 at 1 hour after resuscitation,249.6± 12.0 vs.107.4± 18.2 at 2 hours after resuscitation;MAP (mmHg):82.1±2.1 vs.74.0±2.8 at 1 hour of maintaining MAP of 80 mmHg,107.5±9.3 vs.64.0±5.7 at 1 hour after resuscitation,104.0±9.7 vs.73.0±4.2 at 2 hours after resuscitation;LVSP (mmHg):128.6±7.9 vs.103.8±0.8 at 1 hour of maintaining MAP of 80 mmHg,129.3±± 15.0 vs.99.4±0.0 at 1 hour after resuscitation,127.5± 11.3 vs.97.4±0.0 at 2 hours after resuscitation;+dp/dt max (mmHg/s):6 534.2±± 787.6 vs.5 074.0± 71.7 at 1 hour of maintaining MAP of 80 mmHg,5 961.5 ±± 545.4 vs.4 934.5 ± 510.2 at 1 hour after resuscitation,5 897.4± 350.5 vs.4 534.7 ±489.2 at 2 hours after resuscitation,all P ＜ 0.05].Conclusions HBOC infusion prolonged the survival time,increased survival rate,and improved hemodynamics,cardiac function and tissue oxygen supply in a dose-dependent manner in the early stage of uncontrolled hemorrhagic shock.The recovery effect of 5.0％ HBOC was similar to that of the whole blood.