Heart Rate Variability Responses of Individuals With and Without Saline-Induced Obstructive Sleep Apnea

Vena, Daniel 1, 2 ; Bradley, T. Douglas 2, 3 ; Millar, Philip J. 4, 5 ; Floras, John S. 3, 4 ; Rubianto, Jonathan 2 ; Gavrilovic, Bojan 2 ; Perger, Elisa 2 ; Yadollahi, Azadeh 1, 2

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 2. Toronto Rehabilitation Institute - University Health Network; 3. Department of Medicine, University of Toronto; 4. Toronto General Research Institute, University Health Network; 5. Human Health and Nutritional Sciences, University of Guelph

Although some studies employing heart rate variability (HRV) analysis suggest that obstructive sleep apnea (OSA) is associated with reduced cardiac vagal modulation during sleep and wakefulness, it is not clear whether such changes are due to OSA per se or to co-existing conditions such as obesity or diabetes. To determine the causative effects of OSA on HRV, the present study investigates whether induction of OSA in humans alters sympathetic or cardiac vagal activity. We hypothesize that individuals who develop OSA by saline infusion during sleep will experience autonomic dysregulation, compared to those without saline-induced OSA. Twenty-one normotensive, nonobese (mean BMI 24.5 kg/m2) men (mean age 37 years) underwent a sleep study and blood pressure was measured before and after sleep. Through random assignment, participants were infused with saline during sleep at the minimum rate to keep the vein open (control) or as a bolus of 22 ml/kg body weight (intervention). Participants crossed over to the other study arm one week later. HRV measurements were computed from continuous electrocardiographic recordings pre- and post-saline infusion in the intervention arm. HRV measures computed were: standard deviation of the RR interval (SDRR), and low (LF) and high frequency (HF) power. Compared to sleep apnea severity in the control arm, 8 participants had an increased apnea-hypopnea index by saline infusion (AHI+), and 13 had no change in apnea-hypopnea index by saline infusion (AHI-). In the AHI+ group, systolic blood pressure increased significantly over the period of sleep (p<0.05), while blood pressure was unchanged over sleep in the AHI- group (P>0.1). Changes in LF power from pre- to post-infusion were not different between the groups (both P>0.1).  However, while pre-saline infusion values were similar, post-saline infusion values of SDRR and HF power were lower in the AHI+, compared to the AHI- group (P<0.05 for both). Reduced SDRR combined with reduced HF power represent a reduced and possibly impaired cardiac vagal modulation of the heart in those with saline-induced OSA. By controlling for baseline AHI and using saline infusion to increase the AHI in a subset of participants, our results provide evidence of the causative role of OSA on vagal withdrawal. Over time this can lead to chronic impairments in resting heart rate and blood pressure.  Vagal withdrawal experienced in those with saline-induced OSA might also explain their elevated systolic blood pressure upon waking. These results are the first in humans to demonstrate that acute induction or worsening of OSA causes a form of cardiovascular autonomic dysregulation.