Improved in Vivo Performance of Amperometric Oxygen (PO₂) Sensing Catheters via Electrochemical Nitric Oxide Generation/Release

Abstract

A novel electrochemically controlled release method for nitric oxide (NO) (based on electrochemical reduction of nitrite ions) is combined with an amperometric oxygen sensor within a dual lumen catheter configuration for the continuous in vivo sensing of the partial pressure of oxygen (PO2) in blood. The on-demand electrochemical NO generation/release method is shown to be fully compatible with amperometric PO2 sensing. The performance of the sensors is evaluated in rabbit veins and pig arteries for 7 and 21 h, respectively. Overall, the NO releasing sensors measure both venous and arterial PO2 values more accurately with an average deviation of −2 ± 11% and good correlation (R2 = 0.97) with in vitro blood measurements, whereas the corresponding control sensors without NO release show an average deviation of −31 ± 28% and poor correlation (R2 = 0.43) at time points >4 h after implantation in veins and >6 h in arteries. The NO releasing sensors induce less thrombus formation on the catheter surface in both veins and arteries (p < 0.05). This electrochemical NO generation/release method could offer a new and attractive means to improve the biocompatibility and performance of implantable chemical sensors.

Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO)

“…This approach has been utilized to develop a new generation of multi-lumen catheters in which one lumen is dedicated to generating NO electrochemically to reduce thrombus and microbial biofilm formation on the surface of the catheters. 147,258 …”

“…262 Currently, however, measurements are done in vitro with point-of-care devices intermittently, leaving large gaps of information between blood draws. 258,263 Therefore, developing intravascular sensors that can monitor key chemical species in real time in critically ill patients is an important avenue of research. 264 However, adhesion of platelets, and eventual thrombus formation on the surface of the sensors can occur within a few hours after blood contact, and such processes can not only isolate the chemical sensing area from the bulk of the blood and lead to false analytical results but also increase the risk of emboli or stroke.…”

“…So far, several different NO delivery approaches have been reported for such intravascular oxygen sensors, including coating catheter surface with NONOates, 267,268 covalently attaching NONOates to catheter polymer surface, 269 catalytically generating NO in situ from endogenous RSNOs using embedded copper particles 8,270 and electrochemically modulating NO generation from nitrite. 258 For example, Schoenfisch et al coated outer surfaces of SR catheters with 2 wt% ( Z )-1-[ N -methyl- N -[6–( N -methylammoniohexyl)amino]] diazeniumdiolate (MAHMA/N 2 O 2 ) and demonstrated that the NO release from the catheter lasted more than 20 h in PBS at 37 °C. One control (coated only with MAHMA) and one NO release catheter (coated with MAHMA/N 2 O 2 ) were implanted within the carotid or left femoral arteries in a canine model for 12–23 h. The electrochemical response of the NO-releasing O 2 sensor more closely represented the real arterial blood gas value measured by a benchtop blood-gas analyzer than the control sensor, which had a significant discrepancy starting from the first few hours after the implantation.…”

Automated Online Solid-Phase Derivatization for Sensitive Quantification of Endogenous S-Nitrosoglutathione and Rapid Capture of Other Low-Molecular-Mass S-Nitrosothiols

“…6,12-14 In such methods, total decomposition of RSNOs is desired, but also challenging. Besides, these methods preclude identification of multiple RSNO species because the detection is based on the released NO• and total RSNO level will be determined.…”

Nitric oxide release for improving performance of implantable chemical sensors – A review

“…NO may also be considered as a potential interference for in vivo oxygen sensing. However, Hang et al [47] showed that amperometric O 2 sensing is fully compatible with NO release, as no noticeable amperometric signal changes were observed for the O 2 sensor with NO generation at physiological flux levels. Indeed, Nichols et al [48] evaluated the in vivo glucose recovery of subcutaneously implanted NO-releasing (from saturated NO solution) microdialysis probes in a rat model over 14 d period and reported that intermittent sustained NO release from implanted probe surfaces may improve glucose diffusion for subcutaneously implanted devices by mitigating the foreign body reaction.…”