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

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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.