Changes in fetal baroreceptor sensitivity during intrauterine inflammation in preterm fetal sheep

Abstract

Objective

Baroreflex is a regulatory mechanism that slows the fetal heart rate. This study aimed to investigate the effects of lipopolysaccharide (LPS)-induced endotoxemia on fetal baroreceptor sensitivity in preterm fetal sheep.

Methods

The changes in fetal baroreceptor sensitivity were measured in seven chronically instrumented preterm fetal sheep. Fetal baroreceptor sensitivity was measured in three phases: (A) control phase, defined as the 24 h before the first injection of LPS; (B) acute phase, defined as the 24 h between the first and second injections of LPS; and (C) fetal acidosis phase, defined as the time from the second LPS injection until intrauterine fetal death. Histological examinations of the fetal membrane and umbilical cord were also conducted.

Results

Each fetus developed metabolic acidosis after the second injection of LPS. The fetuses died 24.7 (SD = 6.1) hours after the second injection of LPS. Both the umbilical cord and fetal membranes showed histological evidence of severe inflammation. In total, 163 fetal baroreceptor measurements were performed in this experiment (A, n = 77 times; B, n = 60 times; C, n = 26 times). Fetal baroreceptor sensitivity showed significant differences in all three phases (A: 2.7 [SD = 0.2]; B: 2.5 [SD = 0.2]; and C: 1.5 [SD = 0.2]). Post hoc tests showed that baroreceptor sensitivity in the acidosis phase had decreased significantly compared to that in the control and acute phases (p<.001 and p=.002, respectively).

Conclusions

Fetal baroreceptor sensitivity decreased during fetal acidosis induced by LPSs.

Keywords:

• Fetal acidosis
• fetal baroreceptor sensitivity
• intrauterine fetal death
• intrauterine inflammation
• lipopolysaccharide

Acknowledgements

We would like to thank Hideki Chiba MD, PhD, for providing the pathological analysis.

Disclosure statement

The authors declare that they have no conflict of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author, H.K., upon reasonable request.

Additional information

Funding

The study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology (25462569). The funding source had no role in the collection, analysis, and interpretation of data and in the writing of the manuscript.