OVA-induced airway hyperresponsiveness alters murine heart rate variability and body temperature

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.

Patterns of heart rate variability and cardiac autonomic modulations in controlled and uncontrolled asthmatic patients

“…This is because the present results suggested augmented parasympathetic and depressed sympathetic autonomic modulations in CA compared with UA patients but fail to demonstrate similar differences in autonomic trends when the AS group was compared with HS. To our knowledge, the present study is the first report to state clearly different patterns of cardiac autonomic modulations among controlled and uncontrolled asthmatic patients, although some previous reports gave cues that may support the present hypothesis [ 10 , 11 ]. Cabiddu et al studied HRV in eight patients suffering from difficult-to-control asthma during different stages of sleep [ 10 ].…”

“…The incongruity of our results with previous reports might be explained by the unique design of our study which considered adjustment for MHR and AAT while comparing AS to HS. Alternatively, higher global HRV of CA compared with UA subjects could be explained by the findings of a recent study designed by Domnik et al to assess the impact of allergic sensitization to ovalbumin on HRV in a murine model [ 11 ]. The researchers were able to demonstrate that sensitized mice had decreased HRV prior to ovalbumin challenge, increased HRV during antigen challenge and finally decreased HRV subsequent to the challenge.…”

“…Recent research exploring deranged autonomic functions in certain diseases was largely based on HRV studies [ 2 – 4 ]. Bronchial asthma has received special attention by researchers investigating the impact of autonomic disturbances on the disease etiology [ 5 – 11 ]. Low HRV and predominance of parasympathetic modulations on the heart were demonstrated in some studies [ 5 – 8 ], but not others [ 9 – 11 ].…”

“…Bronchial asthma has received special attention by researchers investigating the impact of autonomic disturbances on the disease etiology [ 5 – 11 ]. Low HRV and predominance of parasympathetic modulations on the heart were demonstrated in some studies [ 5 – 8 ], but not others [ 9 – 11 ]. According to some previous reports, parasympathetic discharge seems to predominate in asthmatic patients irrespective of day-and-night cycle [ 12 ] or physical activity [ 5 ].…”

“…Consequently, results of studies that do not adjust for asthma-associated changes in heart rates, and anti-asthma treatments (AAT), while comparing HRV and autonomic modulations between asthmatic and non-asthmatic subjects are questionable and deserve re-evaluation. Previous reports that failed to show predominance of vagal drive in asthmatic individuals may be biased by heterogeneous patterns of autonomic modulations among asthmatic patients [ 9 – 11 ]. Poor response of difficult-to-control asthma patients to anticholinergic drugs raises the question of whether enhanced vagal drive contributes to the pathogenesis of asthma in these patients [ 19 , 20 ].…”