| Acute normovolemic hemodilution is applied commonly. Its working principle is maintaining blood volume by transfusing cell-free liquid when active blood collection or accidental hemorrhage happened. This procedure can reduce hematocrit, to make blood be diluted. The blood collected actively can be transfused back of necessity, decreasing allogeneic transfusion, to achieve the purpose of autologous transfusion and blood conservation. Accidental hemorrhage happened when severe trauma or intraoperation massive bleeding. When transfusion cannot be immediately employed, blood diluted passively by transfusing cell-free liquid to maintain blood volume due to the patients with rare blood type or other reasons.No matter active or passive hemodilution, plasma or large amounts of liquid is needed including balanced salt solution, albumin solution, artificial plasma substitutes, etc. In recent years, with severe trauma frequently happened and major surgeries needed large volume of blood such as liver transplantation are increasing. Cases with severe hemodilution by plasma or large amounts of liquid are increasing. A trauma patient in our country suffered passive hemodilution, transfusion cannot be immediately employed due to rare blood type and the plasma substitutes were used in a large volume about 3500 m L. In Japan, a rare blood type patient transfused albumin solution about 28000 m L during liver transplantation and hemoglobin concentration decreased to 0.6g/d L. To countries and regions lacking blood resource, the artificial plasma substitutes are particularly important.The common plasma substitutes include dextran, gelatin and hydroxyethyl starch. At present, domestic clinical commonly used artificial plasma substitutes include succinylated gelatin injection Dextran 40 sodium chloride injection(Dextran 40, Dex40),(Gelofusine, GEL), 200/0.5 Hydroxyethyl Starch and sodium chloride injection(Hydroxyethyl Starch 200/0.5, HES200), 130/0.4 Hydroxyethyl Starch and sodium chloride injection(Hydroxyethyl Starch 130/0.4, HES130) and Hydroxyethyl Starch 40 sodium chloride injection(Hydroxyethyl Starch 40, 706), etc. Despite these substitutes are used widely, existing clinical researches showed the usage amount of plasma substitutes is about 500-1500 m L. The clinical researches paid less attention to large volume infusion with plasma substitutes, especially comparison for different plasma substitutes is lacking.Therefore, in this study the severe acute normovolemic hemodilution rat model is established with different plasma substitutes to compare the effects of different plasma substitutes on acid-base balance, electrolyte, physiological parameters and survival rates, etc. And the reason for the differences about these plasma substitutes is analyzed. Looking forward to provide experimental basis for large volume infusion with plasma substitutes in clinical treatmentsand theory reference to improving the level of treatments for severe trauma and massive bleeding patients. This study is divided into four parts: Chapter 1: The blood gas, physiology and survival in severe acute normovolemic hemodilution rat modelNormovolemic hemodilution was performed by withdrawal of blood and simultaneous infusion of plasma substitutes with three steps. Hematocrit is reduced approximately 20% of baseline in each step, expecting to amount to 40% of baseline at the end of hemodilution. Comparing to the baseline, hematocrit, hemoglobin concentration, base excess and central venous oxygen saturation were significantly lower, but blood lactate was significantly higher at the end of hemodilution and 1h after hemodilution. Comparing with the end of hemodilution, hematocrit, hemoglobin concentration and blood lactate were significantly higher, but base excess and central venous oxygen saturation were significantly lower at 1h after hemodilution. Diastolic blood pressure and mean arterial pressure were significantly lower at the beginning of hemodilution and keep this tendency after hemodilution, pulse pressure was significantly higher. Heart rate was significantly higher at 20 min after hemodilution, and keeping higher until the end. The survival rates were 100%, 53.7%, 27.78%, 18.52% and 11.11% at 1-5h after hemodilution.This study showed that acute normovolemic hemodilution rat model reaches severe level. The acid-base disturbance and hypoxia were happened, and the early survival rate reduced significantly. Due to the blood viscosity and systemic vascular resistance were decreasing, diastolic blood pressure and mean arterial pressure were decreasing. To analyze the relationship among every parameter of blood pressure, acidbase balance and hypoxia parameters, regression equations were established with the difference between baseline and 1h after hemodilution. The results showed that mean arterial pressure has a certain relationship with base excess and blood lactate. It indicated that mean arterial pressure was superior to systolic blood pressure, diastolic blood pressure and pulse pressure for reflecting acid-base disturbance and hypoxia injury. It is important to real-time monitoring mean arterial pressure for estimating the degree of the lesion. Chapter 2: The influences of different plasma substitutes on homeostasis parametersAnimals were divided into GEL, HES200, HES130, 706, and Dex40 five groups by the difference of plasma substitutes. Acid-base balance, electrolyte, hypoxia parameters and blood glucose concentration were detected at baseline, the end of hemodilution and 1h after hemodilution. At the end of hemodilution and 1h after hemodilution, potential of hydrogen, base excess and bicarbonate ions concentration were significantly lower in Dex40 group than the others. At 1h after hemodilution blood lactate and potassium ions concentration were significantly higher and central venous oxygen saturation was significantly lower in Dex40 group than the others. The calcium ions concentration in GEL, HES200, HES130 and Dex40 groups were significantly higher at 1h after hemodilution. At the end of hemodilution chloride ions concentration was significantly lower in GEL group than the others. At the end of hemodilution blood glucose concentration was significantly higher in GEL, HES200 and Dex40 groups. At 1h after hemodilution blood glucose concentration was significantly higher in 706 group.The results indicated that Dex40 was inferior to the other plasma substitutes for maintaining acid-base balance and tissue oxygen delivery. Dex40 could cause a significant increase of potassium ions and blood glucose concentration, so patients with severe trauma and massive bleeding should be careful to administration. Chapter 3: The influences of different plasma substitutes on physiological parameters and survivalBlood pressure and heart rate were monitored at different time points, and survival rate were compared in five groups. At the end of the first step of hemodilution, systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure decreased transiently in Dex40 group, and were significantly lower than the others. In the following steps each parameter of blood pressure increased. At 1h after hemodilution mean arterial pressure was significantly lower in Dex40 group than HES200, HES130 and GEL groups. Systolic blood pressure, diastolic blood pressure and mean arterial pressure were significantly higher in HES200 group than 706 group during the hemodilution procedure. Mean arterial pressure were significantly higher in HES200 group than Dex40, 706 and GEL groups at 1h after hemodilution. Heart rate in Dex40 group was significantly higher than GEL and HES200 groups from the second step of hemodilution to 30 min after hemodilution. There was no significant differences in heart rate in each group.The survival rate after 4h from high to low was HES200, HES130, 706, GEL and Dex40.The results indicated that HES200 showed advantage of maintaining mean arterial pressure and improving survival rate. The survival rate after 4h from high to low was HES200, HES130, 706, GEL and Dex40. At the beginning of hemodilution, blood pressure decreased transiently in Dex40 group. Although blood pressure elevated again, Dex40 was still inferior to the other plasma substitutes for maintaining mean arterial pressure. Heart rate in Dex40 group was at a higher level. It may indicated relatively insufficient blood volume. Chapter 4: Analysis of biomechanopharmacology for the mechanical characteristics of the different plasma substitutesColloid osmotic pressure of plasma substitutes influences volume expansion and hemodynamics. The colloid osmotic pressure degree in five groups from high to low was Dex40, 706, GEL, HES130 and HES200 with preparation concentration. Despite the colloid osmotic pressure was significantly higher in Dex40 group than HES200 group, volume expansion effect in HES200 group was better comparing with the changes of systolic blood pressure in chapter 3.The hemorheology properties participate may influence the effects of plasma substitutes. Blood viscosity was measured with different shear rates for resuspended erythrocytes in plasma substitutes. Blood viscosity in HES200 group was lowest at low shear rate, this may relate to its advantage on mean arterial pressure, and the mechanism need to be further discussed in detail.In addition, the influences of different plasma substitutes on erythrocyte aggregation were estimated with viscosity conversion method and dynamic image display method. The hematocrit were 40% and 0.3% in these methods. The results with viscosity conversion method showed that the erythrocyte aggregation degree in five groups from high to low was GEL, 706, HES130, there is no significant influence on erythrocyte aggregation with HES200 and Dex40. The results with dynamic image display method showed that the aggregates appeared firstly in GEL group and the aggregates were the biggest. The aggregates appeared secondly in HES130 and HES200 groups. The last one is Dex40 group, and there is no aggregate in 706 group during the whole study. These results indicated that GEL could induce erythrocyte aggregation with different hematocrit. The mechanism of erythrocyte aggregation influences the effects of different plasma substitutes need to be further discussed.In conclusion, acute normovolemic hemodilution rat model in this study reached severe level. The acid-base disturbance and hypoxia were happened, and the early survival rate reduced significantly. Dex40 was inferior to the other plasma substitutes for maintaining acid-base balance, tissue oxygen delivery and mean arterial pressure. Dex40 could cause a significant increase of potassium ions concentration, so patients with severe trauma and massive bleeding should be careful to administration. HES200 showed advantage of maintaining mean arterial pressure and improving survival rate. After hemodilution, the survival rate from high to low was HES200, HES130, 706, GEL and Dex40.Additionally, analysis of the reason for the differences on these plasma substitutes found that the effects of volume expansion in vivo is not a positive correlation with the colloid osmotic pressure of samples. It indicated that the effects of volume expansion in vivo is not only decided by colloid osmotic pressure, but also the molecular weight of polymers and the metabolic rates, etc. Blood viscosity in HES200 group was lowest at low shear rate, this result may associate with its advantage on mean arterial pressure. GEL can induce erythrocyte aggregation with different hematocrit. The mechanism of erythrocyte aggregation influences the effects of different plasma substitutes need to be further discussed. |
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