Preliminarily Study On The Ability Of Oxygen-carrying Plasma Substitute To Improve Rat Microcirculation Disturbance Induced By Hemorrhagic Shock

Background:Hemorrhagic shock can induce microcirculation disturbance due to inadequate tissue perfusion, which may result in metabolic abnormalities of oxygen and energy or even multiple organ dysfunction syndrome. Thus it is important to restore tissue miercirculation for treatment of hemorrhagic shock. The oxygen-carrying and plasma-expansion aspects are essential for resuscitation fluid. But most of the fluids used in clinic only have expansion ability. So we combined hydroxyethyl starch(HES) and polymerized human placenta hemoglobin (PolyPHb) and denominated it as oxygen-carrying plasma substitute. We hypothesized that it possessed both oxygen-carrying and volume expansion abilities as HES was well studied volume expander and PolyPHb showed excellent oxygen-carrying ability. Previous study had demonstrated the hypothesis by a rat shock model and a blood exchange model. So we are intend to research its effects on improving hemorrhagic-induced microcirculation disturbance.Objective:To build a rat model of severe hemorrhagic shock and mesenteric microcirculation. Then evaluate the therapeutic efficacy of the oxygen-carrying plasma substitute with the model.Methods:50% blood volume were withdrawed from femoral artery to establish a rat microcirculation disturbance model. Then rats were randomly resuscitated with normovolemic fluids including hydroxyethyl starch, red blood cell from rats and the oxygen-carrying plasma substitute. And investigate their effect on mesenteric microcirculation and related enzymes at different times. Some rats were used to investigate the effect on mesenteric microcirculation. MAP, HR, diameter of vessels, blood flow state, and number of rolling and adherent leukocytes were recorded at different time points including baseline, shock, end of resuscitation and 1h after resuscitation. CD11b/CD18 and blood gas were tested at the same time points with arterial blood. The parameters of microcirculatory enzymology included TNF-α,IL-6,ET-1, VEGF, ICAM-1 and NO in plasma that was separated from arterial blood by centrifuging were detected at different times.Results:The rat mesenteric microcirculation parameters showed that microvascular diameter decreased with MAP and HR decreasing after 50% of hemorrhage. The perfusion volume of mesenteric microcirculation were recovered and so did the diameters of vessels after resuscitating. But reperfusion induced leukocytes adhere to vessel wall. The vessel diameters in the three groups were recovered to baseline 1h after resuscitation. The blood gas parameters were partly improved. Besides, the number of adherent leukocytes and CD11b/CD18 were significantly less than the other two groups. After fluid resuscitation, blood gas were partly recovered in the three groups. The level of TNF-α,IL-6,ET-1 and VEGF significantly improved after fluid treatment. TNF-α and ET-1 in HES130 group were lower than the other two at end of resuscitation and 1h after resuscitation separately. IL-6, NO and VEGF in the oxygen-carrying plasma substitute group were significantly lower than HES130 group 1h after resuscitation.Conclusion:The oxygen-carrying plasma substitute had volume expansion effect as traditional plasma substitute and the ability of carrying oxygen as PolyPHb did. And the oxygen-carrying plasma substitute and the rat blood could carry oxygen to the tissues to correct energy metabolism, which might improve microcirculation disturbance because of hypoxia in the end.