Dataset Information

Influence of acute epinephrine infusion on endotoxin-induced parameters of heart rate variability: a randomized controlled trial.

ABSTRACT: To determine whether the acute anti-inflammatory influence of epinephrine (EPI) extends to changes in heart rate variability (HRV) induced by the prototypical inflammatory stimulus, endotoxin (lipopolysaccharide [LPS]).HRV reflects fluctuating cardiac autonomic inputs and is acutely reduced during the systemic inflammation induced by LPS as well as during severe critical illnesses such as sepsis and traumatic injury. While EPI may diminish proinflammatory cytokine release, it is unknown whether this net anti-inflammatory activity extends to HRV.Healthy volunteers (n = 17) were randomized to either saline + LPS (2 ng/kg) or LPS + antecedent EPI infusion (30 ng/kg/min) from -3 to 6 hours relative to LPS. HRV and blood samples were obtained before EPI and LPS as well as hourly afterward. Plasma cytokines were measured by ELISA. Statistical analysis was by repeated measures analysis of variance. This study was registered at Clinicaltrials.gov and is listed under the following ID number: NCT00753402.LPS acutely influenced all measured parameters of HRV including standard deviation of the average beat to beat intervals over a 5-minute period, percentage of interval differences of successive interbeat intervals greater than 50 milliseconds and square root of the mean squared differences, high frequency (HF), low frequency, low frequency/HF, and very low frequency (all P < 0.01). EPI infusion reduced the inflammatory cytokine response to LPS as measured by decreased TNFalpha, IL-6, and IL-8 (P < 0.01). Relative to the saline + LPS group, antecedent EPI infusion was associated with further reductions in parameters of HRV measuring vagal/parasympathetic activity including, percentage of interval differences of successive interbeat intervals greater than 50 milliseconds, square root of the mean squared differences, and HF (P < 0.05).Prior EPI exposure exerts anti-inflammatory influences but also may reduce vagus nerve activity. Hence, acute EPI administration may be protective against early inflammatory challenges but diminish vagal nerve responsiveness to subsequent stimuli.

SUBMITTER: Jan BU

PROVIDER: S-EPMC2856330 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Influence of acute epinephrine infusion on endotoxin-induced parameters of heart rate variability: a randomized controlled trial.

Jan Badar U BU Coyle Susette M SM Oikawa Leo O LO Lu Shou-En SE Calvano Steve E SE Lehrer Paul M PM Lowry Stephen F SF

Annals of surgery 20090501 5

<h4>Objective</h4>To determine whether the acute anti-inflammatory influence of epinephrine (EPI) extends to changes in heart rate variability (HRV) induced by the prototypical inflammatory stimulus, endotoxin (lipopolysaccharide [LPS]).<h4>Summary background data</h4>HRV reflects fluctuating cardiac autonomic inputs and is acutely reduced during the systemic inflammation induced by LPS as well as during severe critical illnesses such as sepsis and traumatic injury. While EPI may diminish proinf ...[more]

PMID: 19387330

Similar Datasets

Project description:Human injury or infection induces systemic inflammation with characteristic neuroendocrine responses. Fluctuations in autonomic function during inflammation are reflected by beat-to-beat variation in heart rate, termed heart rate variability (HRV). In the present study, we determine threshold doses of endotoxin needed to induce observable changes in markers of systemic inflammation, investigate whether metrics of HRV exhibit a differing threshold dose from other inflammatory markers, and investigate the size of data sets required for meaningful use of multiscale entropy (MSE) analysis of HRV.Healthy human volunteers (n = 25) were randomized to receive placebo (normal saline) or endotoxin/lipopolysaccharide (LPS): 0.1, 0.25, 0.5, 1.0, or 2.0 ng/kg administered intravenously. Vital signs were recorded every 30 min for 6 h and then at 9, 12, and 24 h after LPS. Blood samples were drawn at specific time points for cytokine measurements. Heart rate variability analysis was performed using electrocardiogram epochs of 5 min. Multiscale entropy for HRV was calculated for all dose groups to scale factor 40.The lowest significant threshold dose was noted in core temperature at 0.25 ng/kg. Endogenous tumor necrosis factor ? and interleukin 6 were significantly responsive at the next dosage level (0.5 ng/kg) along with elevations in circulating leukocytes and heart rate. Responses were exaggerated at higher doses (1 and 2 ng/kg). Time domain and frequency domain HRV metrics similarly suggested a threshold dose, differing from placebo at 1.0 and 2.0 ng/kg, below which no clear pattern in response was evident. By applying repeated-measures analysis of variance across scale factors, a significant decrease in MSE was seen at 1.0 and 2.0 ng/kg by 2 h after exposure to LPS. Although not statistically significant below 1.0 ng/kg, MSE unexpectedly decreased across all groups in an orderly dose-response pattern not seen in the other outcomes.By using repeated-measures analysis of variance across scale factors, MSE can detect autonomic change after LPS challenge in a group of 25 subjects using electrocardiogram epochs of only 5 min and entropy analysis to scale factor of only 40, potentially facilitating MSE's wider use as a research tool or bedside monitor. Traditional markers of inflammation generally exhibit threshold dose behavior. In contrast, MSE's apparent continuous dose-response pattern, although not statistically verifiable in this study, suggests a potential subclinical harbinger of infectious or other insult. The possible derangement of autonomic complexity prior to or independent of the cytokine surge cannot be ruled out. Future investigation should focus on confirmation of overt inflammation following observed decreases in MSE in a clinical setting.

Project description:In the recent years, short-term heart rate variability (HRV) describing complex variations of beat-to-beat interval series that are mainly controlled by the autonomic nervous system (ANS) has been increasingly analyzed to assess the ANS activity in different diseases and under various conditions. In contrast to long-term HRV analysis, short-term investigations (<30 min) provide a test result almost immediately. Thus, short-term HRV analysis is suitable for ambulatory care, patient monitoring and all those applications where the result is urgently needed. In a previous study, we could show significant variations of 5-min HRV indices according to age in almost all domains (linear and nonlinear) in 1906 healthy subjects from the KORA S4 cohort. Based on the same group of subjects, general gender-related influences on HRV indices are to be determined in this study. Short-term 5-min HRV indices from linear time and frequency domain and from nonlinear methods (compression entropy, detrended fluctuation analysis, traditional and segmented Poincaré plot analysis, irreversibility analysis, symbolic dynamics, correlation and mutual information analysis) were determined from 782 females and 1124 males. First, we examined the gender differences in two age clusters (25-49 years and 50-74 years). Secondly, we investigated the gender-specific development of HRV indices in five age decade categories, namely for ages 25-34, 35-44, 45-54, 55-64 and 65-74 years. In this study, significant modifications of the indices according to gender could be obtained, especially in the frequency domain and correlation analyses. Furthermore, there were significant modifications according to age in nearly all of the domains. The gender differences disappeared within the last two age decades and the age dependencies disappeared in the last decade. To summarize gender and age influences need to be considered when performing HRV studies even if these influences only partly differ.

Dataset Information

Influence of acute epinephrine infusion on endotoxin-induced parameters of heart rate variability: a randomized controlled trial.

Publications

Influence of acute epinephrine infusion on endotoxin-induced parameters of heart rate variability: a randomized controlled trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure