Biphasic changes in fetal heart rate variability in preterm fetal sheep developing hypotension after acute on chronic lipopolysaccharide exposure

Christopher A. Lear, Joanne O. Davidson, Lindsea C. Booth, Guido Wassink, Robert Galinsky, Paul P. Drury, Mhoyra Fraser, Laura Bennet, Alistair J. Gunn

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)


Perinatal exposure to infection is highly associated with adverse outcomes. Experimentally, acute, severe exposure to gram-negative bacterial lipopolysaccharide (LPS) is associated with increased fetal heart rate variability (FHRV). It is unknown whether FHRV is affected by subclinical infection with or without acute exacerbations. We therefore tested the hypothesis that FHRV would be associated with hypotension after acute on chronic exposure to LPS. Chronically instrumented fetal sheep at 0.7 gestation were exposed to a continuous low-dose LPS infusion (n = 12, 100 ng/kg over 24 h, followed by 250 ng·kg-1·24 h-1 for a further 96 h) or the same volume of saline (n = 10). Boluses of either 1 μg LPS or saline were given at 48, 72, and 96 h. Low-dose infusion was not associated with hemodynamic or FHRV changes. The first LPS bolus was associated with tachycardia and suppression of nuchal electromyographic activity in all fetuses. Seven of twelve fetuses developed hypotension (a fall in mean arterial blood pressure ≥5 mmHg). FHRV was transiently increased only at the onset of hypotension, in association with increased cytokine induction and electroencephalogram suppression. FHRV then fell before the nadir of hypotension, with transient suppression of short-term FHRV. After the second LPS bolus, the hypotension group showed a biphasic pattern of a transient increase in FHRV followed by more prolonged suppression. These findings suggest that infection-related hypotension in the preterm fetus mediates the transient increase in FHRV and that repeated exposure to LPS leads to progressive loss of FHRV.

Original languageEnglish
Pages (from-to)R387-R395
Number of pages9
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number4
Publication statusPublished - 15 Aug 2014
Externally publishedYes


  • Fetal heart rate variability
  • Fetal sheep
  • Lipopolysaccharide
  • Tolerance

Cite this