Day-night variation in heart rate variability changes induced by endotoxaemia in healthy volunteers

Abstract

Background: Morbidity and mortality in response to sepsis may be dependent on clock time for the initiation of sepsis. Endotoxaemia, an experimental model for systemic inflammation, induces alterations in sympatico-vagal balance in the autonomic nervous system (ANS). The activity of sympathetic and parasympathetic activity can be estimated by measuring heart rate variability (HRV). Based on the intimate link between ANS and the inflammatory response, we hypothesized, that HRV changes seen during endotoxaemia would be different based on time of the day the endotoxaemia is initiated. We investigated day/night variation in endotoxaemia-induced changes in HRV.

Methods: A randomized, crossover study with 12 healthy men (age 18-31) was conducted. Endotoxaemia were induced by lipopolysaccharide (LPS) endotoxin 0.3 ng/kg b.w. in two visits (day visit and night visit). At the day visit, endotoxaemia were induced at 12:00 h, and at the night visit it was induced at 24:00 h. Holter recordings were started 1 h before administration of LPS, and continued for 10 h. Time-domain and frequency-domain parameters of HRV were analysed.

Results: A total of nine persons finished the study with valid recordings. Endotoxaemia at both night and day resulted in a significant depression in HRV parameters high-frequency power (HF), low-frequency power (LF), standard deviation of normal-to-normal (NN) intervals, root mean square of successive differences and proportion of NN50 divided by total number of NNs (P<0.001). The ratio LF/HF and mean heart rate significantly increased by endotoxaemia (P<0.001). At night-time endotoxaemia, a more pronounced depression of LF, HF and SDNN (P<0.01) and a more pronounced increase in the ratio of LF/HF and mean heart rate (P<0.01) occurred compared with day-time endotoxaemia.

Conclusion: Endotoxaemia induced changes in HRV exhibit a day-night difference. This difference may have clinical consequences in patients with sepsis.