Effects of different plasma expanders on rats subjected to severe acute normovolemic hemodilution.

BACKGROUND: Plasma expanders are widely used for acute normovolemic hemodilution (ANH). However, existing studies have not focused on large-volume infusion with colloidal plasma expanders, and there is a lack of studies that compare the effects of different plasma expanders. METHODS: The viscosity, hydrodynamic radius (Rh) and colloid osmotic pressure (COP) of plasma expanders were determined by a cone-plate viscometer, Zetasizer and cut-off membrane, respectively. Sixty male rats were randomized into five groups with Gelofusine (Gel), Hydroxyethyl Starch 200/0.5 (HES200), Hydroxyethyl Starch 130/0.4 (HES130), Hydroxyethyl Starch 40 (HES40), and Dextran40 (Dex40), with 12 rats used in each group to build the ANH model. ANH was performed by the withdrawal of blood and simultaneous infusion of plasma expanders. Acid-base, lactate, blood gas and physiological parameters were detected. RESULTS: Gel had a lower intrinsic viscosity than HES200 and HES130 (P < 0.01), but at a low shear rate in a mixture of colloids, red cells and plasma, Gel had a higher viscosity (P < 0.05 or P < 0.01, respectively). For hydroxyethyl starch plasma expanders, the COP at a certain concentration decreases from 11.1 mmHg to 6.1 mmHg with the increase of Rh from 10.7 nm to 20.2 nm. A severe ANH model, with the hematocrit of 40% of the baseline level, was established and accompanied by disturbances in acid-base, lactate and blood gas parameters. At the end of ANH and 60 min afterward, the Dex40 group showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) decreased significantly in all groups at the end of ANH. The DBP and MAP in the Dex40 group further decreased 60 min after the end of ANH. During the process of ANH, the Dex40 group showed a drop and recovery in SBP, DBP and MAP. The DBP and MAP in the HES200 group were significantly higher than those in the other groups at some time points (P < 0.05 or P < 0.01). CONCLUSION: Gel had a low intrinsic viscosity but may increase the whole blood viscosity at low shear rates. Rh and COP showed a strong correlation among hydroxyethyl starch plasma expanders. Dex40 showed a worse outcome in maintaining the acid-base balance and systemic oxygenation compared to the other plasma expanders. During the process of ANH, Dex40 displayed a V-shaped recovery pattern for blood pressure, and HES200 had the advantage in sustaining the DBP and MAP at some time points.

Conjugation with 20 kDa dextran decreases the autoxidation rate of bovine hemoglobin.

Haemoglobin-based oxygen carrier (HBOC) is highly susceptible to autoxidation that renders a series of tissue and cellular toxicities. HBOC is prepared by chemical modification of haemoglobin (Hb), which typically increases the autoxidation rate of Hb. Thus, it is necessary to decrease the autoxidation of HBOC. In the present study, two dextran-bHb conjugates (dex20-bHb and dex40-bHb) were prepared by conjugation with 20 kDa or 40 kDa dextrans, where the thiol group of Cys-93(ß) was reversibly protected. The autoxidation rate of bHb was decreased by conjugation with 20 kDa dextran and maintained by conjugation with 40 kDa dextran. In order to understand the low autoxidation rate of dex20-bHb, the effects of aldehyde modification and dextran on the autoxidation rate of dex20-bHb were investigated. The high oxygen affinity, high tetramer stability and dextran itself were found to decrease the autoxidation rate of dex20-bHb. The conjugated dextran had a predominant effect on decreasing the autoxidation rate of bHb, which was particularly promising for the potential development of safe HBOCs. Conjugation with dextran is of general significance to decrease the oxidation process of the heme-containing proteins, such as Hb and myoglobin.

In vitro and in vivo investigation of the novel Dex-bHb as oxygen carriers.

The development of hemoglobin-based oxygen carriers (HBOCs) is a persistent and urgent need in biomedicine. As a potential HBOCs, Dextran-hemoglobin (Dex-bHb) has been developed over the past years. The novel Dex-bHb, whose thiol group of Cys-93(ß) was reversibly protected, was produced and the characteristics were evaluated in our previous study. Herein, blood compatibility was characterized in terms of the red blood cell aggregation and hemolysis rate in vitro, and Dex-bHb showed no obvious effects. After intravenous administration of Dex-bHb to golden Syrian hamsters with hemorrhages shock, it showed mean arterial pressure recovery, blood flow increase and the organ protection from serious hemorrhage injury. Consequently, Dex-bHb is hopeful to be a safe and available blood substitute.

Hypertonic Saline Dextran Ameliorates Organ Damage in Beagle Hemorrhagic Shock.

OBJECTIVE: The goal of this study was to investigate the effect of hypertonic saline with 6% Dextran-70 (HSD) resuscitation on organ damage and the resuscitation efficiency of the combination of HSD and lactated ringers (LR) in a model of hemorrhage shock in dogs. METHODS: Beagles were bled to hold their mean arterial pressure (MAP) at 50 ± 5 mmHg for 1 h. After hemorrhage, beagles were divided into three groups (n = 7) to receive pre-hospital resuscitation for 1 h (R1): HSD (4 ml/kg), LR (40 ml/kg), and HSD+LR (a combination of 4 ml/kg HSD and 40 ml/kg LR). Next, LR was transfused into all groups as in-hospital resuscitation (R2). After two hours of observation (R3), autologous blood was transfused. Hemodynamic responses and systemic oxygenation were measured at predetermined phases. Three days after resuscitation, the animals were sacrificed and tissues including kidney, lung, liver and intestinal were obtained for pathological analysis. RESULTS: Although the initial resuscitation with HSD was shown to be faster than LR with regard to an ascending MAP, the HSD group showed a similar hemodynamic performance compared to the LR group throughout the experiment. Compared with the LR group, the systemic oxygenation performance in the HSD group was similar but showed a lower venous-to-arterial CO2 gradient (Pv-aCO2) at R3 (p < 0.05). Additionally, the histology score of the kidneys, lungs and liver were significantly lower in the HSD group than in the LR group (p < 0.05). The HSD+LR group showed a superior hemodynamic response but higher extravascular lung water (EVLW) and lower arterial oxygen tension (PaO2) than the other groups (p < 0.05). The HSD+LR group showed a marginally improved systemic oxygenation performance and lower histology score than other groups. CONCLUSIONS: Resuscitation after hemorrhagic shock with a bolus of HSD showed a similar hemodynamic response compared with LR at ten times the volume of HSD, but HSD showed superior efficacy in organ protection. Our findings suggest that resuscitation with the combination of HSD and LR in the pre-hospital setting is an effective treatment.

[Hemorrheological changes in irreversible hemorrhagic shock].

OBJECTIVE: To observe the characteristics of changes in hemorheology at the early stage of irreversible hemorrhagic shock in a rodent model. METHODS: Rodent model of irreversible hemorrhagic shock was reproduced. Animals were randomized into 4 groups. In the first group, survival rate and mean arterial pressure (MAP) in 180 minutes were observed after hemorrhagic shock (S group). In the second group, animals were sacrificed soon after hemorrhagic shock (S0 group). In the third group, animals were sacrificed 60 minutes after hemorrhagic shock (S1 group). In the fourth group, animals were sacrificed 120 minutes after hemorrhagic shock (S2 group). Blood samples of animals of S0, S1 and S2 were all obtained before hemorrhagic shock. Blood lactate, hemorheological parameters, red blood cell (RBC) deformability and RBC aggregation index were determined. RESULTS: Mean blood loss of S group was (22.9+/-3.8) ml/kg, constituting about (38.1+/-6.3)% of total blood volume. At 60, 120 and 180 minutes after hemorrhagic shock, survival rates were 100%, 72% and 64%, respectively. Compared with baseline, 0, 60 and 120 minutes after hemorrhagic shock, blood lactate increased significantly (all P<0.01), but 120 minutes after hemorrhagic shock, it decreased significantly compared with 0 minute after hemorrhagic shock (P<0.05). Compared with baseline, 0 minute and 60 minutes after hemorrhagic shock, blood viscosity was found to be decreased at shear rate of 10 s(-1), 60 s(-1) and 100 s(-1) (all P<0.01); 120 minutes after hemorrhagic shock, at shear rate of 10 s-1 and 60 s(-1), blood viscosity decreased significantly (both P<0.01); 0, 60 and 120 minutes after hemorrhagic shock, plasma viscosity, RBC deformability and RBC aggregation index at shear rates of 600 s(-1), 800 s(-1) and 1 000 s(-1) decreased significantly (all P<0.01). CONCLUSION: At the early stage of irreversible hemorrhagic shock, blood lactate increased significantly, and decreased afterwards. These indicate reversal of deterioration of metabolism. At different time after the early stage of irreversible hemorrhagic shock, blood and plasma viscosity, RBC deformability and aggregation index lowered significantly and did not improve. Changes in viscosity and RBC aggregation are different from the changes in late stage, and this indicates that hemorheological disorders should be corrected in the treatment at the early stage after hemorrhagic shock.