TITLE: Heart Rate Variability Parameters for Assessing Autonomic Responses to Brief Rectal Distention in Patients with Irritable Bowel Syndrome
AUTHORS: M Khawar Ali, Shiyuan Gong, Jiande Chen, Borko Nojkov, Colin Burnett

[DESCRIPTION]
Heart rate variability (HRV) has been used to measure autonomic nervous system (ANS) activity noninvasively. The purpose of this study was to identify the most suitable HRV parameters for ANS activity in response to brief rectal distension (RD) in patients with Irritable Bowel Syndrome (IBS). IBS patients participated in a five-session study. During each visit, an ECG was recorded for 15 min for baseline values and during rectal distension. For rectal distension, a balloon was inflated in the rectum and the pressure was increased in steps of 5 mmHg for 30 s; each distension was followed by a 30 s rest period when the balloon was fully deflated (0 mmHg) until either the maximum tolerance of each patient was reached or up to 60 mmHg. The time-domain, frequency-domain and nonlinear HRV parameters were calculated to assess the ANS activity. The values of each HRV parameter were compared between baseline and RD for each of the five visits as well as for all five visits combined. The sensitivity and robustness/reproducibility of each HRV parameter were also assessed. The parameters included the Sympathetic Index (SI); Root Mean Square of Successive Differences (RMSSD); High-Frequency Power (HF); Low-Frequency Power (LF); Normalized HF Power (HFn);
Normalized LF Power (LFn); LF/HF; Respiratory Sinus Arrhythmia (RSA); the Poincare Plot’s SD1, SD2 and their ratio;
and the pNN50, SDSD, SDNN and SDNN Index. Data from 17 patients were analyzed and compared between baseline and FD and among five sessions. The SI was found to be the most sensitive and robust HRV parameter in detecting the ANS response to RD. Out of nine parasympathetic parameters, only the SDNN and SDNN Index were sensitive enough to detect the parasympathetic modulation to RD during the first visit. The frequency-domain parameters did not show any change in response to RD. It was also observed that the repetitive RD in IBS patients resulted in a decreased autonomic response due to habituation because the amount of change in the HRV parameters was the highest during the first visit but diminished during subsequent visits. In conclusion, the SI and SDNN/SDNN Index are most sensitive at assessing the autonomic response to rectal distention. The autonomic response to rectal distention diminishes in repetitive sessions, demonstrating the necessity of randomization for repetitive tests












[STEPS]
SECTION: Methods
1. Twenty-two patients with IBS (constipation-dominant or IBS-C) were recruited initially. Nineteen patients had completed all five visits and recordings throughout the study. Out of the nineteen patients, two patients were excluded because of their HRV data were considered outliers. 
Since each patient will serve as his/her own control, the actual proportion of IBS subtypes in recruited patients should not affect the study outcomes.
Each participant came to the clinic five time throughout the study. 
SECTION: Methods
2. All medications known to affect the gut will be discontinued 48 h before each session. 
SECTION: Methods
3. The patients were fasted overnight and given arectal enema (250ml) to clean the rectum. After a 30-min rest, a polyvinyl catheter attached with a non-compliance polyethylene bag (500ml capacity and 10cm long) will be inserted and placed 5-15cm from the anal verge.
SECTION: Methods
5. After the 15 min rest(“baseline”), the bag will be distended using an FDA-approved barostat device at 60 ml/min until the maximum tolerance.
Rectal distention was performed at different pressures from 5 mmHg to the maximum tolerable pressure with an increment of 5 mmHg. 
Each distension lasted for 30s and was followed by a 30s rest period when the balloon was deflated.

6. During the distention period (“Rectal Distention”), the patient will be asked to circle the following sensations:1) first sensation,2) urge to defecate, 3) discomfort or pain and 4) maximal tolerance.
 electrocardiogram (ECG) was recorded at the rectal distention period for each individual to assess their autonomic function. 
SECTION: Methods
4. An electrocardiogram (ECG) was recorded for 15 min at baseline to assess their autonomic function (through analyzing the HRV data, described below).
Placement of the electrodes: place the RA electrode under the right clavical within the rib cage frame; place the LA
electrode under the left clavicle within the rib cage frame; place the LL electrode on the lower left
abdomen within the rib cage frame).
7. The interbeat interval (RR interval) signal was calculated from the recorded and refined (after removing the segments of the ECG signal with noise, removing ectopic beats, and inserting interbeat wherever the peak was missed) ECG signal to calculate the HRV parameters; the Sympathetic Index (SI), Root Mean Square of Successive Differences (RMSSD), Respiratory Sinus Arrythmia (RSA) and SD1and SD2 of the Poincare Plot and their ratio (SD2/SD1) were calculated by using MATLAB code developed by the authors. The frequency-domain parameters of the SDSD, SDNN, and SDNN Index and HF, LF, HFn, LFn and LF/HF were calculated by using previously validated software developed in the lab. 
The robustness/reproducibility of each HRV parameter was evaluated by comparing their values among each visit as described below.


SECTION: Statistical analysis
8. A Shapiro–Wilk normality test was performed on each HRV parameter before each comparison. If the parameter was normally distributed, the paired t-test was applied to investigate the difference between the baseline and rectal distension. Otherwise, if not normally distributed, a Wilcoxon test was performed to investigate the differences. To test the reproducibility of the HRV parameters, the baseline and RD values of each visit were compared. The baseline values of all the five visits were compared by using a one-way ANOVA for the normally distributed data and a Kruskal–Wallis test for the data that were not normally distributed, followed by a Dunn’s multiple comparison test. The procedure was repeated by using HRV values during rectal distension and compared among 5 visits.