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

提出了一种在体同时测量血流量和血气的新方法。该方法基于对血气、血液温度、pH等生理参数敏感的化学物质的体内荧光测定法，将荧光染料包封在脂质体中，使其进入血液循环。采用逆相蒸发法制备了磷脂酰胆碱脂质体。胆固醇的加入能很好地维持荧光物质，活化的甲氧基聚乙二醇减少了网状内皮系统对脂质体的摄取。使用聚碳酸酯膜过滤器标准化脂质体的大小。当使用直径小于8 μ m的脂质体时，在肠系膜血管中观察到的流速与用红细胞观察到的流速没有差异。该脂质体给药至少一周无栓塞和毒性，经多次试验最终获得的光学系统为：氩激光经声光调制器调制，激发光和信号光经塑料光纤传输，荧光强度用光子计数法测定。由于荧光的弛豫时间通过Stern-Volmer方程与氧浓度相关，因此从信号光的寿命确定脂质体悬浮液的氧张力。利用该系统成功地进行了离体实验和麻醉大鼠在体实验中的氧分压测量。该系统用于连续监测CO_2张力、局部温度等生理参数的研究正在进行中。

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.