Non-Invasive Monitoring of pH and Oxygen Using Miniaturized Electrochemical Sensors in an Animal Model of Acute Hypoxia

Abstract

BackgroundOne of the most prevalent causes of fetal hypoxia leading to stillbirth is placental insufficiency. Hemodynamic changes evaluated with Doppler ultrasound have been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. As a first step, the present work aimed to evaluate the performance of miniaturized electrochemical sensors in continuous monitoring of oxygen and pH changes in a model of acute hypoxia-acidosis. MethodspH and oxygen electrochemical sensors were evaluated in a ventilatory hypoxia rabbit model. The ventilator hypoxia protocol included three differential phases: basal (100% FiO2), hypoxia-acidosis period (10% FiO2) and recovery (100% FiO2). Sensors were tested in blood tissue (ex vivo sensing) and in the muscular tissue (in vivo sensing). pH electrochemical and oxygen sensors were evaluated at the same day of insertion (short-term evaluation) and pH electrochemical sensors were also tested after 5 days of insertion (long-term evaluation). pH and oxygen sensing were registered during all the ventilatory hypoxia protocol (basal, hypoxia-acidosis and recovery) and were compared with blood gas metabolites results from carotid artery catheterization (EPOC® blood analyzer). Finally, histological assessment was performed on the site of the sensor’s insertion. One-way ANOVA was used for the analysis of the evolution of acid-based metabolites and electrochemical sensor signaling results; T-test was used for pre and post calibration analyses; and chi-square analyses for categorical variables. ResultsAt the short-term evaluation, both pH and oxygen electrochemical sensors distinguished the basal and hypoxia-acidosis periods in the in vivo and ex vivo sensing. However, only the ex vivo sensing detected recovery period. At the long-term evaluation, pH electromechanical sensor signal seemed to lose sensibility. Finally, histological assessment revealed no signs of alteration at the same day of evaluation (short-term), whereas at the long-term evaluation sub-acute inflammatory reaction adjacent to the site of the implantation was detected. ConclusionsThe use of miniaturized electrochemical sensors open a new generation of tools for continuous monitoring of hypoxia-acidosis, especially indicated in high risk pregnancies. Further studies including more tissue-compatible material would be required in order to improve the long-term electromechanical sensing.