Development of an in vivo real-time measurement system of nitric oxide and superoxide and their clinical applications

导管式一氧化氮传感器的开发：首先，我们评估了体内一氧化氮传感器的基本性能。使用饱和NO气体的纯水，传感器的灵敏度约为580 pA/nM-NO。该传感器对NO也有很高的选择性。硝酸甘油输注后，麻醉大鼠腹主动脉血浆NO水平升高至nM水平。其次，将体内NO传感器包裹在4F导管中，研制出导管式NO传感器原型。将传感器插入麻醉犬的胸主动脉。乙酰胆碱（ACh）输注后，血浆NO水平瞬间升高。经L-NMMA抑制NO合成后，ach诱导的血浆NO水平升高明显低于L-NMMA前。最后，我们开发了一种导管式一氧化氮传感器，用于近端血管的一氧化氮测量。在检测尖端的边缘固定一个软尖端。将传感器插入麻醉犬的冠状窦。冠脉内灌注乙酰胆碱可使血浆NO水平升高至5 nM。总之，新开发的导管式一氧化氮传感器具有良好的性能，可用于内皮功能的临床评价。超氧化物传感器的研制：通过化学修饰将超氧化物歧化酶固定在铂丝上制备超氧化物。该传感器安装在流量池式测量系统中。将分离的器官（心脏、肝脏和肾脏）加载到系统中，可以成功地测量这些器官释放的超氧化物水平。

Development of a catheter-type NO sensor : First, we evaluated the basic performance of an in vivo NO sensor. Using a NO gas-saturated pure water, the sensor showed a sensitivity of about 580 pA/nM-NO. The sensor also demonstrated high selectivity to NO. When nitroglycerin was infused, plasma NO level in the abdominal aorta of an anesthetized rat increased to some nM level. Secondly, a proto-type catheter-type NO sensor was developed by encasing the in vivo NO sensor in a 4F catheter. The sensor was inserted into the thoracic aorta of an anesthetized dog. Plasma NO level increased transiently by acetylcholine (ACh) infusion. After inhibition of NO synthesis by L-NMMA, the ACh-induced increase in plasma NO level was significantly lower than that before L-NMMA. Finally, we have developed a catheter-type NO sensor for NO measurement in the proximal vessels. A soft tip was fixed at the edge of the detection tip. The sensor was inserted into the coronary sinus of an anesthetized dog. Intra-coronary infusion of ACh increased plasma NO level up to 5 nM. In conclusion, the newly developed catheter-type NO sensors demonstrated satisfying performance and would be applicable to clinical evaluation of endothelial function.Development of a superoxide sensor : A superoxide was prepared by fixing SOD on a Pt wire with some chemical modification. The sensor was located in a flow-cell-type measurement system. Isolated organs (heart, liver, and kidney) were loaded into the system, and superoxide level released from these organs could be measured successfully.