title: Biphasic changes in fetal heart rate variability in preterm fetal sheep developing hypotension after acute on chronic lipopolysaccharide exposure.
abstract: 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.
authors.affiliation: Department of Physiology, and.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lear
authors.affiliation: Department of Physiology, and.
authors.forename: Joanne O
authors.initials: JO
authors.lastname: Davidson
authors.affiliation: Department of Physiology, and.
authors.forename: Lindsea C
authors.initials: LC
authors.lastname: Booth
authors.affiliation: Department of Physiology, and.
authors.forename: Guido
authors.initials: G
authors.lastname: Wassink
authors.affiliation: Department of Physiology, and.
authors.forename: Robert
authors.initials: R
authors.lastname: Galinsky
authors.affiliation: Department of Physiology, and.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Drury
authors.affiliation: Department of Physiology, and The Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Mhoyra
authors.initials: M
authors.lastname: Fraser
authors.affiliation: Department of Physiology, and.
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
authors.affiliation: Department of Physiology, and aj.gunn@auckland.ac.nz.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D015415:Biomarkers / Q000097:blood; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001919:Bradycardia / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D004562:Electrocardiography; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005318:Fetal Heart / Q000503:physiopathology*; D005323:Fetal Monitoring / Q000379:methods; D005865:Gestational Age; D006340:Heart Rate, Fetal; D006863:Hydrogen-Ion Concentration; D007022:Hypotension / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides; D011247:Pregnancy; D018805:Sepsis / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D012756:Sheep; D013610:Tachycardia / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008070:Lipopolysaccharides; D019344:Lactic Acid
keywords: fetal heart rate variability; fetal sheep; lipopolysaccharide; tolerance