Development of a method for simultaneous measurement of blood flow and blood gases

提出了一种活体同时测量血流量和血气的新方法。该方法基于对血气、血温、pH等生理参数敏感的化学物质的体内荧光检测。荧光染料被包裹在脂质体中，以便进入血液循环。以磷脂酰胆碱为原料，采用反相蒸发法制备了多层脂质体。胆固醇的加入能够很好地维持荧光化学物质，活化的甲氧基聚乙二醇会减少网状内皮系统对脂质体的摄取。用聚碳酸酯薄膜滤膜对脂质体的大小进行了标准化。当使用直径小于8微米的脂质体时，肠系膜血管的血流速度与红细胞的血流速度没有差异。经多次试验，最终得到的光学系统为：利用声光调制器调制激光，用塑料光纤传输激发光和信号光，用光子计数法测定荧光强度。根据Stern-Volmer方程，荧光的驰豫时间与氧浓度有关，根据信号光的寿命来确定脂质体悬浮液的氧张力。利用该系统成功地测量了体外实验和体内实验中的氧分压，并将该系统应用于CO_2张力、局部温度等生理参数的连续监测。

A novel method to measure blood flow and blood gases simultaneously in vivo was developed. This method is based on in vivo fluorometry of chemical substances sensitive to physiological parameters such as blood gases, blood temperature, pH and so on. The fluorescent dye was encapsulated in liposomes so as to administer into blood circulation. The liposome was also used to measure blood flow velocity using transit time method.Multilamellar liposome was fabricated from phosphatydylcholine using reverse-phase evaporation methods. Addition of cholesterol enabled to sustain fluorescent chemicals well, and activated methoxypolyethylene glycol reduced uptake of liposome by reticulo-endothelial system. The size of liposome was standardized using polycarbonate membrane filter. When liposome with less than 8mum of diameter were used, the flow velocity observed in mesenteric vessel showed no difference with that observed with erythrocytes. The administration of this liposome caused no embolism and toxicity for at least a week.The optical system finally attained after several trials is as follows : argon-laser was used modulating with Acousto-Optic modulator, exciting and signal laser was transferred with plastic optical fibers, and the fluorescence intensity was determined using photon counting. Since the relaxation time of the fluorescence is related to the oxygen concentration by Stern-Volmer equation, exygen tension of liposome suspension was determined from the lifetime of the signal light. Using this system we measured successfully the partial pressure of oxygen in vitro experiment and also in vivo experiment using anesthetized rat.The application of this system for the continuous monitoring of physiological parameters including CO_2 tension, and local temperature are underway.