Beneficial effects of hemoglobin-based oxygen carriers on early resuscitation in rats with uncontrolled hemorrhagic shock

Abstract

To investigate the early resuscitation effect of hemoglobin-based oxygen carriers (HBOC) in rats with uncontrolled hemorrhagic shock. 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/dt max) were determined in another 10 rats, and cardiac output (CO) and tissue oxygen supply (DO2) were observed in the rest 8 rats. (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]. 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.