Non-invasive monitoring of pH and oxygen using miniaturized electrochemical sensors in an animal model of acute hypoxia

Abstract

Background One 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 the continuous monitoring of oxygen and pH changes in a model of acute hypoxia-acidosis. Methods pH and oxygen electrochemical sensors were evaluated in a ventilatory hypoxia rabbit model. The ventilator hypoxia protocol included 3 differential phases: basal (100% FiO2), the hypoxia-acidosis period (10% FiO2) and recovery (100% FiO2). Sensors were tested in blood tissue (ex vivo sensing) and in muscular tissue (in vivo sensing). pH electrochemical and oxygen sensors were evaluated on the 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 throughout the ventilatory hypoxia protocol (basal, hypoxia-acidosis, and recovery) and were compared with blood gas metabolites results from carotid artery catheterization (obtained with the EPOC blood analyzer). Finally, histological assessment was performed on the sensor insertion site. One-way ANOVA was used for the analysis of the evolution of acid-based metabolites and electrochemical sensor signaling results; a t-test was used for pre- and post-calibration analyses; and chi-square analyses for categorical variables. Results At the short-term evaluation, both the pH and oxygen electrochemical sensors distinguished the basal and hypoxia-acidosis periods in both the in vivo and ex vivo sensing. However, only the ex vivo sensing detected the recovery period. In the long-term evaluation, the pH electrochemical sensor signal seemed to lose sensibility. Finally, histological assessment revealed no signs of alteration on the day of evaluation (short-term), whereas in the long-term evaluation a sub-acute inflammatory reaction adjacent to the implantation site was detected. Conclusions Miniaturized electrochemical sensors represent a new generation of tools for the continuous monitoring of hypoxia-acidosis, which is especially indicated in high-risk pregnancies. Further studies including more tissue-compatible material would be required in order to improve long-term electrochemical sensing.

Miniaturized Electrochemical Sensors to Monitor Fetal Hypoxia and Acidosis in a Pregnant Sheep Model

“…Previous studies with electrochemical sensors were designed similar to those used in this study demonstrated different sensibilities. In an adult rabbit model with a ventilatory hypoxia induction, the pO 2 electrochemical sensor inserted in the skeletal muscle presented lower sensibility in comparison with the sensibility described here [12]. These differences may be explained with different reasons.…”

“…This could be because acidosis produced in the tissue by cells affected by hypoxia takes some time to reach the blood flow, producing a delay in the response in blood-based measurement. Finally, as observed with the oxygen sensor, the sensibilities observed for the pH sensing differ from a previous study [12]. Again, these differences may be explained by the same three reasons as discussed above on the differences observed with the oxygen sensor.…”

“…In this regard, miniaturized electrochemical sensors insertable through a needle would be required in order to monitor fetal acid-base status. Previous studies from our group have demonstrated that miniaturized electrochemical sensors could monitor oxygen or pH changes continuously in a model of ventilatory hypoxia in adult rabbits [12][13][14]. The development of a multiparametric electrochemical sensor aiming to monitor oxygen and pH at the same time would offer a great advantage in the monitoring of these pregnancies.…”

A Review on Magnetic Induction Spectroscopy Potential for Fetal Acidosis Examination

“…The low oxygen in tissue causes acute and chronic hypoxia, which induces low oxygen in the blood called hypoxemia. This finally results in an acidosis condition (low blood pH) [ 10 ].…”

“…Apart from pH, a few other parameters have been observed to change significantly during acidosis. In study [ 10 ], it was noticed that , pH and bicarbonate concentrations decreased, whereas lactate and potassium concentrations increased. However, was the parameter that most quickly reflected changes in the acid-base status, reaching its minimum value within 2.38 min.…”