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 the 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 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.ResultsAt 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.ConclusionsMiniaturized 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.
Highlights
One of the most prevalent causes of fetal hypoxia leading to stillbirth is placental insufficiency
One electrode was a bare platinum wire used as a counter, another was a modified silver wire (Ag/AgCl) used as a pseudoreference electrode (PRE), and the last was a membranemodified platinum wire with Nafion used as a working electrode (WE)
Sampling and histological analyses After finalizing the ventilatory hypoxia induction protocol, the animals were sacrificed with pentobarbital (200 mg/kg, IV) and the muscular tissue surrounding the insertion area of the sensors was carefully excided, fixed
Summary
One of the most prevalent causes of fetal hypoxia leading to stillbirth is placental insufficiency. Whereas acute and severe episodes of hypoxia have been related to intrauterine death, periods of moderate hypoxia that persist over time may have deleterious consequences for fetal growth and development [2]. Both acute and chronic prenatal hypoxia induce fetal anabolic metabolism followed by fetal hypoxemia and acidosis [3, 4]. Doppler ultrasound evaluation could identify these hemodynamical changes [7] and has been described as a useful tool for fetal monitoring as it has been correlated with blood gas results [8]
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