267395 Development an Evaluation of a Perfluorocarbon-Based Oxygen Carrier Mixed with HES 6% and Blood
In recent decades the field that presents the greatest attention from the scientific community is the research on the circulatory system and particularly the tissue oxygenation. The reason for this is that the main causes of deaths worldwide are related to cardiovascular diseases and hemorrhage; the basic principle of treatment is the control of the bleeding site and replace of the lost volume with blood transfusions. Although this is a routine procedure, there are risks associated with its performance as the transmission of pathogens and changes in blood properties such as viscosity, pH and affinity of hemoglobin for oxygen. An alternative for the multiple disadvantages of the blood transfusions are the perfluorocarbon-based oxygen carrier (PFCOCs) which are direct emulsions O/W that can replace blood in its function of transport oxygen to tissues.
The objective of this study is to develop a stable O / W perfluorocarbon emulsion, with perfluoro-octyl bromide (PFOB) (30% v/v) as disperse phase, an electrolyte solution as the continuous phase and soybean lecithin as surfactant; able to transport oxygen intravascular for cases of acute hemorrhage.
Perfluorocarbon emulsions have been widely studied and characterized, leading to the understanding of the system and its properties, but their influence on the real intravascular scenario has not been objectively analyzed in terms of the interaction between the emulsion and blood properties. For this reason, an in vitro model of normovolemic hemodilution was implemented to analyze the effects of PFCOCs on blood rheology and predict PFCOCs performance when infused.
For the development of the emulsion, the most favorable composition of surfactant is determined by analyzing the stability of the emulsion evaluating the particle size distribution and rheological behavior over time, by varying the concentration of surfactant 3.5% w/v, 4.5% w/v and 5.5% w/v. The behavior at the microscopic level is set using the technique of dynamic light scattering DLS with the Zetasizer Nano ZS from Malvern® and the rheological behavior is measured from steady-state testing using the AR-G2 Magnetic Bearing Rheometer from TA Instruments ® with a concentric cylinder geometry at shear rates of 0.1 to 1000 s-1 and 1000 to 0.1 s-1.
For the normovolemic hemodilution, fresh porcine blood was collected and stored in blood transfusion bags using CPDA-1 as anticoagulant, and mixed with hydroxyethyl starch (HES Tetraspan 6%, B. Braun). The in vitro procedure consisted of 4 exchanges, each one replacing 40% of volemia. In the first two exchanges, volume was replaced with HES and in the last two with a mixture of 20% HES and 80% PFCOCs. After each exchange a sample was taken, characterized microscopically at 100X, and macroscopically measuring viscosity with the rheometer.
As a result of the normovolemic hemodilution, viscosity of the mixture increased with the increasing perfluorocarbon emulsion-to-blood volume ratio, up to 9.4 cP after the last exchange. There is particle aggregation in the blood-emulsion mixture with sizes of 17 µm and they may impede the flow of erythrocytes. In the in vivo intravascular application these aggregates may induce occlusion of the micro vascular system.