Early sinusoidal heart rate patterns and heart rate variability to assess hypoxia-ischaemia in near-term fetal sheep.

Abstract

•Therapeutic hypothermia needs to be started as early as possible in the first 6h after acute injury caused by hypoxia-ischaemia (HI), but the severity and timing of HI are often unclear. In this study we evaluated whether measures of heart rate variability (HRV) might provide early biomarkers of HI. •The duration but not magnitude of suppression of HRV power and conversely increased sample entropy of the heart rate were associated with severity of HI, such that changes in the first 3h did not discriminate between groups. •Relative changes in HRV power bands showed different patterns between groups and therefore may have the potential to evaluate the severity of HI. •Aberrant fetal heart rate patterns and increased arginine vasopressin levels in the first hour after moderate and severe HI were correlated with loss of EEG power after 3days' recovery, suggesting potential utility as early biomarkers of outcome. Therapeutic hypothermia is partially neuroprotective after acute injury caused by hypoxia-ischaemia (HI), likely because the timing and severity of HI are often unclear, making timely recruitment for treatment challenging. We evaluated the utility of changes in heart rate variability (HRV) after HI as biomarkers of the timing and severity of acute HI. Chronically instrumented fetal sheep at 0.85 gestational age were exposed to different durations of umbilical cord occlusion to produce mild (n=6), moderate (n=8) or severe HI (n=8) or to sham occlusion (n=5). Heart rate (HR) and HRV indices were assessed until 72h after HI. All HI groups showed suppressed very low frequency HRV power and elevated sample entropy for the first 3h; more prolonged changes were associated with greater severity of HI. Analysis of relative changes in spectral power showed that the moderate and severe groups showed a shift towards higher HRV frequencies, which was most marked after severe HI. This shift was associated with abnormal rhythmic HR patterns including sinusoidal patterns in the first hour after HI, and with elevated plasma levels of arginine vasopressin, which were correlated with subsequent loss of EEG power by day3. In conclusion, absolute changes in HRV power in the first 3h after acute HI were not significantly related to the severity of HI. The intriguing relative shift in spectral power towards higher frequencies likely reflects greater autonomic dysfunction after severe HI. However, sinusoidal HR patterns and elevated vasopressin levels may have utility as biomarkers of severe HI.