Interplay Between the Acute Inflammatory Response and Heart Rate Variability in Healthy Human Volunteers

Abstract

The autonomic nervous system and the inflammatory response are intimately linked. Heart rate variability (HRV) analysis is a widely used method to assess cardiac autonomic nervous system activity, and changes in HRV indices may correlate with inflammatory markers. Here, we investigated whether baseline HRV predicts the acute inflammatory response to endotoxin. Second, we investigated whether the magnitude of the inflammatory response correlated with HRV alterations. Forty healthy volunteers received a single intravenous bolus of 2 ng/kg endotoxin (LPS, derived from Escherichia coli O:113). Of these, 12 healthy volunteers were administered LPS again 2 weeks later. Heart rate variability was determined at baseline (just before LPS administration) and hourly thereafter until 8 h after LPS administration. Plasma cytokine levels were determined at various time points. Baseline HRV indices did not correlate with the magnitude of the LPS-induced inflammatory response. Despite large alterations in HRV after LPS administration, the extent of the inflammatory response did not correlate with the magnitude of HRV changes. In subjects who were administered LPS twice, inflammatory cytokines were markedly attenuated after the second LPS administration, whereas LPS-induced HRV alterations were similar. Heart rate variability indices do not predict the acute inflammatory response in a standardized model of systemic inflammation. Although the acute inflammatory response results in HRV changes, no correlations with inflammatory cytokines were observed. Therefore, the magnitude of endotoxemia-related HRV changes does not reflect the extent of the inflammatory response.