Abstract
Altered autonomic (ANS) tone in chronic respiratory disease is implicated as a factor in cardiovascular co-morbidities, yet no studies address its impact on cardiovascular function in the presence of murine allergic airway (AW) hyperresponsiveness (AHR). Since antigen (Ag)-induced AHR is used to model allergic asthma (in which ANS alterations have been reported), we performed a pilot study to assess measurement feasibility of, as well as the impact of allergic sensitization to ovalbumin (OVA) on, heart rate variability (HRV) in a murine model. Heart rate (HR), body temperature (TB), and time- and frequency-domain HRV analyses, a reflection of ANS control, were obtained in chronically instrumented mice (telemetry) before, during and for 22 h after OVA or saline aerosolization in sensitized (OVA) or Alum adjuvant control exposed animals. OVA mice diverged significantly from Alum mice with respect to change in HR during aerosol challenge (P < 0.001, Two-Way ANOVA; HR max change Ctrl = +80 ± 10 bpm vs. OVA = +1 ± 23 bpm, mean ± SEM), and displayed elevated HR during the subsequent dark cycle (P = 0.006). Sensitization decreased the TB during aerosol challenge (P < 0.001). Sensitized mice had decreased HRV prior to challenge (SDNN: P = 0.038; Low frequency (LF) power: P = 0.021; Low/high Frequency (HF) power: P = 0.042), and increased HRV during Ag challenge (RMSSD: P = 0.047; pNN6: P = 0.039). Sensitized mice displayed decreased HRV subsequent to OVA challenge, primarily in the dark cycle (RMSSD: P = 0.018; pNN6: P ≤ 0.001; LF: P ≤ 0.001; HF: P = 0.040; LF/HF: P ≤ 0.001). We conclude that implanted telemetry technology is an effective method to assess the ANS impact of allergic sensitization. Preliminary results show mild sensitization is associated with reduced HRV and a suppression of the acute TB-response to OVA challenge. This approach to assess altered ANS control in the acute OVA model may also be beneficial in chronic AHR models.
Highlights
Asthma is an inflammatory condition of the airways (AW) characterized by airway hyperresponsiveness (AHR), inflammatory cell infiltration and reversible bronchoconstriction, which, on a chronic basis, progresses to AW remodeling (Boulet et al, 1999; Holgate, 2008; Lougheed et al, 2010)
Asthma is often modeled in animals through allergic induction of AHR, which is characterized by a decrease in the bronchoconstrictive threshold and Abbreviations: AHR, Airway Hyperresponsiveness; Alum, Alum Adjuvant Control Group; autonomic nervous system (ANS), Autonomic Nervous System; AW, Airway; Bronchioalveolar lavage (BAL), Bronchoalveolar Lavage; high Frequency (HF), High Frequency Power; heart rate (HR), Heart Rate; heart rate variability (HRV), Heart Rate Variability; Low frequency (LF), Low Frequency Power; MCh, Methacholine; OVA, Ovalbumin; PAW, Airway Pressure; pNN6, Percentage of consecutive normal R-R intervals differing by more than 6 ms; RMSSD, Square root of the mean of the sum of squares of successive differences between normal R-R intervals; respiratory resistance (RRS), Total Respiratory Resistance; standard deviation of all normal R-R intervals (SDNN), Standard deviation of normal R-R intervals; TI, Inspiratory Time; TB, Body Temperature; VT, Tidal Volume; white blood cell (WBC), White Blood Cell
The present study is the first to examine the murine integrative phenotype associated with the OVA model, as reflected by HR, TB and HRV measurements, which are linked to autonomic nervous system (ANS) control (Thayer et al, 2011)
Summary
Asthma is an inflammatory condition of the airways (AW) characterized by airway hyperresponsiveness (AHR), inflammatory cell infiltration and reversible bronchoconstriction, which, on a chronic basis, progresses to AW remodeling (Boulet et al, 1999; Holgate, 2008; Lougheed et al, 2010). Asthma is often modeled in animals through allergic induction of AHR, which is characterized by a decrease in the bronchoconstrictive threshold and Abbreviations: AHR, Airway Hyperresponsiveness; Alum, Alum Adjuvant Control Group; ANS, Autonomic Nervous System; AW, Airway; BAL, Bronchoalveolar Lavage; HF, High Frequency Power; HR, Heart Rate; HRV, Heart Rate Variability; LF, Low Frequency Power; MCh, Methacholine; OVA, Ovalbumin; PAW, Airway Pressure; pNN6, Percentage of consecutive normal R-R intervals differing by more than 6 ms; RMSSD, Square root of the mean of the sum of squares of successive differences between normal R-R intervals; RRS, Total Respiratory Resistance; SDNN, Standard deviation of normal R-R intervals; TI, Inspiratory Time; TB, Body Temperature; VT, Tidal Volume; WBC, White Blood Cell. We assessed the utility of a chronically instrumented murine model of acute ovalbumin (OVA) sensitization, in which we investigated the effect of sensitization and antigen (Ag; i.e., OVA) challenge on the regulation of heart rate (HR) using time- and frequency-domain HRV analysis of www.frontiersin.org
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