Acute breathing patterns in healthy and heart disease participants during cycling at different levels of immersion

Respiratory Physiology & Neurobiology 235 (2017) 1–7

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Acute breathing patterns in healthy and heart disease participants during cycling at different levels of immersion Andrée Dionne a , Mario Leone b,d , David E. Andrich c , Louis Pérusse a , Alain Steve Comtois c,d,∗ a

Department of kinesiology, Université Laval, 2300 rue de la Terrasse, Quebec, (QC), G1V 0A6, Canada Department of Health Sciences, University of Quebec in Chicoutimi, 555 University boulevard, Saguenay, (QC), G7H 2B1, Canada c Department of Physical Activity Sciences, University of Quebec in Montreal, C.P. 8888, succ, Centre-ville, Montreal, (QC), H3C 3P8, Canada d Centre for Interdisciplinary Research on Quality and Healthy Lifestyle, University of Quebec in Chicoutimi, 555 University boulevard, Saguenay, (QC), G7H 2B1, Canada b

a r t i c l e

i n f o

Article history: Received 15 April 2016 Received in revised form 15 September 2016 Accepted 22 September 2016 Available online 23 September 2016 Keywords: Water stationary bike Water immersion Ventilatory flow Heart disease

a b s t r a c t We aimed to determine the effect of aquatic cycling and different levels of immersion on respiratory responses in healthy and heart disease (HD) volunteers. Thirty-four age matched volunteers, 21 HD and 13 healthy controls (HC) took part in this study. The ventilatory pattern, phase 1 VE and steady-state ventilatory responses to progressive exercise from 40 to peak rpm, were measured while participants exercised on a water stationary bike (WSB) at different levels of immersion. No effect of immersion was observed on steady-state respiratory responses in the HD group, but immersion reduced VE phase 1 by ∼79% at pedaling cadences of 40, 50 and 60 rpm. In conclusion, immersion at hips and xiphoid process blunted the fast drive to breathe in the HD group. This transient effect on the respiratory response to immersed exercise cannot be considered a contraindication for exercise in HD individuals. © 2016 Elsevier B.V. All rights reserved.

1. Introduction Exercise is an important part of cardiac rehabilitation contributing to improved longevity and quality of life. However, only 12% of older patients with heart disease (HD) participate in cardiac rehabilitation programs (Forman et al., 2011). Training in water, such as pool base exercise programs, has the potential to make exercise more attractive to individuals that are limited by their medical and/or physical condition on land. However, the quantification of the effort intensity in water has been challenging in traditional activities such as running and calisthenics with different levels of immersion. (Hall et al., 1998; Nakanishi et al., 1999; Shono et al., 2000). Specifically the physical characteristics of individuals influencing the resistance provided by water, together with either the use of arms and/or the loss of balance, make it more difficult to accurately estimate exercise intensity applied.

∗ Corresponding author at: Department of Physical Activity Sciences, University of Quebec in Montreal, C.P. 8888, succ, Centre-ville, Montreal, (QC), H3C 3P8, Canada. E-mail addresses: [email protected] (A. Dionne), [email protected] (M. Leone), [email protected] (D.E. Andrich), [email protected] (L. Pérusse), [email protected] (A.S. Comtois). http://dx.doi.org/10.1016/j.resp.2016.09.011 1569-9048/© 2016 Elsevier B.V. All rights reserved.

In recent years, the challenges posed by the quantification of aquatic exercise have been addressed by a new training modality—water stationary bicycle (WSB)—that makes exercise intensity quantification possible through external power output (Garzon et al., 2014a,b; Leone et al., 2014). Although several studies have assessed the physiological responses to cycling in water (Brechat et al., 1999; Chen et al., 1996; Christie et al., 1990; Connelly et al., 1990; Costill, 1971; Dressendorfer et al., 1976; Sheldahl et al., 1987, 1984), very few have reported on patients affected by heart disease (HD) (Hanna et al., 1993; McMurray, 1988). The viscosity and buoyancy of the water contribute to the reduction of body weight and the hydrostatic pressure causes a cephalad fluid shift. This epiphenomenon has been shown to increase cardiac output and appears to be beneficial during water immersed exercise (Brechat et al., 2013; Garzon et al., 2014a,b). Little is known, however, about the effect of the hydrostatic pressure exerted on the thorax of HD patients, which could be detrimental to their breathing pattern. In fact, the increase in the intrathoracic blood volume caused by the cephalad shift in blood volume packs the pulmonary capillaries and competes for air space in the lungs resulting in a reduction of 30 to 50% of the static and dynamic lung compliance, respectively (Taylor and Morrison, 1993).

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Previous studies in healthy individuals show that during immersed exercise the hydrostatic pressure that acts against both the anterior abdominal and chest wall at the xiphoid process can cause a reduction in both the inspiratory capacity and the expiratory reserve volume (de Andrade et al., 2016). Modifying these two components of the respiratory system may affect the breathing pattern to exercise in both healthy and HD patients. Also, it is well established that minute ventilation (VE ) increases rapidly in response to exercise − phase 1 VE response. Phase 1 VE response is typically out of proportion to the metabolic requirements and has been associated with proprioception of limb movement, more specifically to leg movement frequency during walking, running or cycling. Recently, Phase 1 VE (the fast increase to breathe) has been shown proportional to the cadence on an ergocycle on dryland (Duffin, 2013). However, the effect of water immersion on Phase 1 VE response remains unknown, in particular in patients suffering from HD. Thus, the purpose of this study was to investigate the effect of different levels of immersion during cycling on the respiratory responses to exercise in both healthy and heart disease individuals. We hypothesized that different levels of immersion (either the hips or the xiphoid process) affect the ventilatory pattern similarly in both HD patients and healthy individuals during a progressive exercise on a WSB.

2. Methods 2.1. Participants Thirty-four men and women participated in this study. The heart disease group (HD) was composed of 21 patients (19 men and 2 women), 14 affected by coronary heart disease (CHD) and 7 with congestive heart failure (CHF) with a mean age of 64.7 ± 7.4 years. The HD group included stable patients for at least three months, non-smokers, with either a past myocardial infarction, a history of coronary disease documented by angiography, angioplasty or by nuclear imaging testing, or CHF. Only 2 participants were taking a single medication, all others were on a combined therapy. Even though many participants were taking ␤-adrenergic blocking agents, this medication exerts its primary influence during exercise on the cardiovascular system, without any discernible effect on respiration (Agostoni et al., 2010; Sheldahl et al., 1984). The etiology of all CHF participants was ischemic of origin, the mean ejection fraction (EF) was 36.5% and two participants had an internal pacemaker defibrillator. The control group was composed of 13 healthy, age- matched participants (5 men and 8 women). The healthy control (HC) participants recruited for this study were nonsmokers, without any known cardiovascular or pulmonary disease. Apparently healthy participants with high blood pressure that was controlled with medication with a dose that was unchanged for the past three months were accepted. In addition, a preliminary analysis indicated that there was no significant difference between CHD and CHF patients, and between both women and men, thus, it was agreed to pool the data for further analysis to form two groups, respectively, the HD (CHD and CHF) group and the HC group. Participants from both groups did not have previous experience of underwater pedaling. This study was approved by the Ethics Committee of the University of Québec in Montréal (UQAM). Before testing, each participant was informed of the objective of the study, the testing procedures and provided their written informed consent to participate in the study. All HD participants obtained consent from their treating physicians in order to participate, according to the American College of Sports Medicine (ACSM) guidelines (ACSM, 2006). The baseline characteristics of participants are presented in Table 1.

Table 1 Participant characteristics. HD(n = 21)

Healthy(n = 13)

p

Age (years) Height (m) Weight (kg) BMI HRpeak (bpm) VO2 peak (ml/kg/min) EF (%) in CHF

64.7 (7.8) 1.71 (0.1) 83.2 (16.2) 28.2 (4.4) 119 (23) 18.6 (4.9) 36.5 (10.3)

61.0 (6.3) 1.69 (0.1) 78.6 (15.3) 27.6 (5.5) 131 (17) 23.7 (6.4)*

0.142 0.510 0.419 0.724 0.098 0.012

Medical treatment (n) ACE-inhibitors ␤-blockers ARA CCB

14 18 5 8

2 1 2

Means ± (S.D.). HRpeak and VO2 peak represent the highest values reached by each participant at calf immersion (land analog); BMI: body mass index; ACE: angiotensin converting enzyme; ARA: angiotensin receptor blocker; CCB: calcium channel blocker; EF: ejection fraction; CHF, congestive heart failure; HD: subjects with heart disease; * p ≤. 05 significant difference between groups.

2.2. Experimental conditions Research activities were carried out in a pool at either UQAM or College Édouard Montpetit Sport Complexes at a water temperature of 29 ◦ C, which is considered as a thermoneutral temperature during exercise (Sheldahl et al., 1984). All testing sessions were separated by at least 48 h.

2.3. Experimental procedure Cycling in water was done on a water stationary bicycle (WSB, Hydrorider, Bologna, Italy) with the resistance offered by the four paddles on the pedaling mechanism set to maximum length, as described by (Leone et al., 2014). The WSB was then placed at the appropriate pool depth allowing the participants to be immersed to calf, hip or xiphoid process level. Immersion to the calf was intended to measure respiratory parameters without the contribution of hydrostatic pressure. All three tests were conducted with the same WSB. Therefore, testing at the calf level ensured that the pedaling mechanism was completely immersed in order to reproduce comparable experimental conditions. Before immersion into the pool, each participant was fitted with a facial mask (Hans Rudolph, U.S.A.) so that no leaks were present. The calibrated turbine was then fitted to the mask and connected to the portable metabolic unit. The unit was attached to a 2-m pole that maintained the unit approximately 1 m above the water surface near the head of the participant. Once immersed, the participant sat on the WSB and resting ventilatory parameters where collected for three minutes. Afterwards, the participants were instructed to pedal. Pedalling cadence was measured with a pedal rpm meter (Cateye Echowell F2, Taiwan) and controlled voluntarily by the subject. The exercise protocol began at a pedal cadence of 40 rpm. Cadence was then increased every 2 min by 10 rpm until at least one of the following was obtained: 85% of calculated maximum heart rate, a score of 16 on the Borg scale or an inability to reach and maintain cadence (ACSM, 2006). The final stage reached was then defined as the peak value and did not represent maximum value. All breathing variables were averaged over the last 30 s of each 2 min stages. A more detailed analysis of the phase 1 VE of hyperpnoea was calculated as the difference in VE before cadence changed (average of last 10 s) and VE 10 s after the cadence change for all different immersion levels (Duffin, 2013).

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Table 2 Ventilatory parameters during exercise at different levels of water immersion and pedaling cadences on a water stationary bike. VARIABLES

40 rpm

VE C (l/min) VE H (l/min) VE X (l/min) VT /TI C (l/s) VT /TI H (l/s) VT /TI X (l/s) TI /TTOT C TI /TTOT H TI /TTOT X FETCO2 C (%) FETCO2 H (%) FETCO2 X (%) VE C (l/min) VE H (l/min) VE X (l/min) VT /TI C (l/s) VT /TI H (l/s) VT /TI X (l/s) TI /TTOT C TI /TTOT H TI /TTOT X FETCO2 C (%) FETCO2 H (%) FETCO2 X (%)

50 rpm

Healthy

HD

p

ES

Healthy

HD

p

ES

21.4 ± 6.5† 18.1 ± 3.9 15.9 ± 4.0 0.83 ± 0.3† 0.71 ± 0.20 0.64 ± 0.17 0.44 ± 0.04 0.43 ± 0.06 0.42 ± 0.04 5.29 ± 0.71 5.22 ± 0.51 5.07 ± 0.67 60 rpm 37.5 ± 9.4 39.4 ± 5.2 37.7 ± 8.2 1.35 ± 0.36 1.46 ± 0.23 1.31 ± 0.24 0.46 ± 0.03†§ 0.45 ± 0.05 0.48 ± 0.03 5.52 ± 0.53 5.45 ± 0.48 5.31 ± 0.68

24.5 ± 6.8 22.8 ± 5.3 21.9 ± 4.7 1.00 ± 0.30 0.97 ± 0.25 0.91 ± 0.19 0.40 ± 0.04 0.40 ± 0.04 0.40 ± 0.03 4.88 ± 0.53 4.98 ± 0.53 4.79 ± 0.48

0.191 0.009 <0.001 0.102 0.005 <0.001 0.036 0.101 0.090 0.063 0.188 0.158

0.5 1.0 1.4 0.6 1.1 1.5 1.0 0.6 0.6 0.7 0.5 0.5

30.8 ± 6.9 31.4 ± 9.0 29.3 ± 7.2 1.24 ± 0.31 1.26 ± 0.33 1.19 ± 0.26 0.41 ± 0.04 0.41 ± 0.04 0.41 ± 0.04 4.99 ± 0.53 5.11 ± 0.62 4.95 ± 0.59

0.181 0.074 0.016 0.052 0.013 0.001 0.026 0.047 0.021 0.016 0.180 0.060

0.5 0.7 0.9 0.7 1.0 1.4 1.1 0.9 0.9 0.9 0.5 0.7

41.7 ± 9.2‡ 45.7 ± 8.7 44.6 ± 9.4 1.63 ± 0.4‡ 1.79 ± 0.32 1.71 ± 0.34 0.43 ± 0.08 0.42 ± 0.04 0.43 ± 0.03 5.05 ± 0.60 5.06 ± 0.73 4.86 ± 0.73

0.226 0.029 0.039 0.058 0.004 0.001 0.258 0.043 <0.001 0.031 0.107 0.083

0.5 0.9 0.8 0.7 1.2 1.4 0.5 0.7 1.5 0.8 0.6 0.6

27.6 ± 6.1† 26.1 ± 6.2 23.3 ± 5.7 1.03 ± 0.3† 0.98 ± 0.27 0.87 ± 0.21 0.45 ± 0.03 0.45 ± 0.05 0.45 ± 0.05 5.45 ± 0.50 5.41 ± 0.60 5.35 ± 0.58 Peak rpm 68.4 ± 26.4† 69.7 ± 31.7 57.5 ± 19.7 2.40 ± 0.98† 2.39 ± 1.10 1.97 ± 0.72 0.47 ± 0.05 0.48 ± 0.03 0.49 ± 0.05 5.30 ± 0.70 5.17 ± 0.50 5.12 ± 0.70

60.9 ± 21.7 67.0 ± 16.0 63.7 ± 15.1 2.28 ± 0.82 2.53 ± 0.61 2.39 ± 0.62 0.44 ± 0.04 0.44 ± 0.03 0.44 ± 0.04 4.95 ± 0.61 4.81 ± 0.63 4.70 ± 0.72

0.375 0.777 0.305 0.721 0.648 0.083 0.018 0.004 0.002 0.344 0.256 0.798

0.3 0.1 0.4 0.1 0.2 0.6 0.9 1.3 1.1 0.6 0.7 0.6

Mean ± SD; p indicates between group significant differences (p ≤ 0.05); ES, between group effect sizes: low effect = 0.2, moderate effect = 0.5, high effect = 0.8; Within group significant differences (p ≤ 0.05): †Calf vs Xiphoid; ‡Calf vs Hip; §Hip vs Xiphoid. Heart disease: HD; Calf immersion: C; Hip immersion: H; Xiphoid immersion: X; Minute ventilation: VE ; Mean inspiratory flow: VT /TI ; Ratio of inspiratory time to total breath cycle time: TI /TTOT ; Expired fraction of end tidal CO2 : FETCO2 ,

2.4. Ventilatory measurements During all tests, ventilation (VE ), tidal volume (VT ), respiratory frequency (RF), inspiratory time (TI ), expiratory time (TE ), total breath cycle time (TTOT ), ratio of inspiratory time to total breath cycle time (TI /TTOT ), mean inspiratory flow (VT /TI ), and expired fraction of end tidal CO2 (FETCO2 ) were measured or calculated from the measurements obtained with a portable metabolic analyser

Table 3 Effect sizes within group between calf, hip and xiphoid process immersion at 40 to peak rpm. Healthy

VE 40 VE 50 VE 60 VE peak VT /TI 40 VT /TI 50 VT /TI 60 VT /TI peak TI /TTOT 40 TI /TTOT 50 TI /TTOT 60 TI /TTOT peak FETCO2 40 FETCO2 50 FETCO2 60 FETCO2 peak Phase 1 40 Phase 1 50 Phase 1 60 Phase 1 peak

HD

C vs H

C vs X

H vs X

C vs H

C vs X

H vs X

0.6 0.2 0.2 0.0 0.5 0.2 0.3 0.0 0.2 0.0 0.3 0.1 0.1 0.1 0.1 0.3 0.6 0.0 0.3 0.1

1.0 0.7 0.0 0.5 0.8 0.7 0.2 0.5 0.5 0.0 0.6 0.3 0.3 0.2 0.3 0.3 0.3 0.1 0.5 0.5

0.6 0.5 0.2 0.5 0.4 0.4 0.6 0.5 0.2 0.0 0.7 0.3 0.3 0.1 0.2 0.1 0.3 0.1 0.3 0.6

0.3 0.1 0.5 0.3 0.2 0.1 0.4 0.3 0.3 0.3 0.3 0.1 0.2 0.2 0.0 0.2 0.2 0.3 0.9 0.3

0.4 0.2 0.3 0.2 0.4 0.2 0.2 0.1 0.3 0.3 0.3 0.2 0.2 0.1 0.3 0.4 0.8 0.9 0.6 0.7

0.2 0.3 0.1 0.2 0.2 0.2 0.2 0.2 0.0 0.3 0.2 0.1 0.4 0.3 0.3 0.2 0.6 0.4 0.2 0.4

ES (effect sizes): low effect = 0.2, moderate effect = 0.5, high effect = 0.8. Heart disease: HD; Calf immersion: C; Hip immersion: H; Xiphoid immersion: X; Minute ventilation: VE (l/min); Mean inspiratory flow: VT /TI (l/s); Ratio of inspiratory time to total breath cycle time: TI /TTOT ; Expired fraction of end tidal CO2 : FETCO2 (%): Phase 1 VE (l/min).

(Cosmed, K4b2, Rome, Italy). Breath-by-breath data for each test were initially examined to exclude outliers caused by sighs, coughs and other breathing aberrations, such as swallowing. Afterwards, all breath-by-breath aforementioned variables were averaged over the last 30 s of each two minute stages of the incremental exercise on the WSB. The portable metabolic analyser was calibrated before each test following the manufacturer’s instructions (User’s manual K4b2, 2006) and has been validated by several authors (Duffield et al., 2004; Hausswirth et al., 1997; McLaughlin et al., 2001). Briefly, before each participant and in the following order, gas calibration was performed using a two gas calibration (Cal 1 and Cal 2) composed for Cal 1 of 20.9% O2 and N2 balance and Cal 2 of 16% O2 , 5% CO2 and N2 balance. The turbine volume calibration was done using a 3L syringe where 8 syringe pumps were executed. The volume calibration was performed to achieve less than 3.5% error on volume (Miller et al., 2005).

2.5. Statistical analysis Data are presented as mean ± standard deviation. All statistical analyses were performed using SPSS for Windows (SPSS Inc., Ver. 16, Chicago, IL, USA) and Sigma plot (Systat Software Inc., Ver. 11, San Jose, Ca, USA). Normal distribution of each variable was assessed using the Shapiro-Wilk tests. All respiratory parameters were analysed using a mixed-design ANOVA for repeated measures with cadence (40, 50, 60 and peak rpm) and immersion (calf, hip and xiphoid-process) as within-subject factors, and groups (Healthy vs HD) as between-subject factors. The Holm-Sidak–correction for post hoc comparison was used when significant interactions were identified. Independent t-tests were used to ensure that there were no significant differences between men and women in each group (HD, Healthy) and also between coronary and CHF patients in the cardiac group (HD). P-values ≤0.05 were considered to indicate statistical significance. Effect size (ES) were calculated and presented using Cohen’s D coefficients.

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Fig. 1. Tidal volume as a function of the respiratory cycle. A–D) the ascending slopes represent the VT /TI for both HD and Healthy groups. * p ≤ 0.05 significant difference between xiphoid process and calf for Healthy group; ** p ≤ 0.05 significant difference between calf and hip for cardiac group; *** p ≤ 0.05 significant difference between both groups. VT , tidal volume; TI , inspiratory time; rpm, pedaling cadence: rpm, measured for both groups HD and Healthy at calf, hip, xiphoid process levels of immersion, respectively.

3. Results 3.1. Effect of immersion level on ventilatory function during cycling Table 2 summarizes the values of respiratory parameters for each of the four exercise intensities as well as the three immersion levels in healthy and HD groups. Overall, the mixed-design ANOVA revealed a between group significant difference for VE and VT /TI as a function of pedaling cadence (F(6, 34) = 2.85, p=0.011, ␩p 2 =0.08; F(6, 34) = 3.20, p=0.005, ␩p 2 =0.09, respectively). In contrast, the mixed-design ANOVA revealed no significant differences for TI /TTOT and FETCO2 (F(6, 34) = 0.52, p=0.794, ␩p 2 =0.02; F(6, 34) = 0.235, p=0.965, ␩p 2 =0.01, respectively). At calf immersion there were generally no significant differences in ventilatory parameters between groups at any pedaling intensity. However, the effect of immersion (hip and xiphoid) increased both statistical significance and the magnitude of differences between groups for most variables.

ES coefficients ranged from moderate to high (≥ 0.4). For sake of clarity, only the ventilatory parameters that show moderate to high changes are presented. The clinical relevance of the differences in ventilatory function for healthy controls and HD participants while exercising at different immersion levels was determined by effect size (ES) and is summarized in Table 3. Several ventilatory variables displayed moderate to high ES coefficients in the HD group. Namely, differences between calf and hip were observed for VE , Phase 1 VE and VT /TI at 60 rpm. Between calf and xiphoid immersion levels, moderate to high ES were observed for VT /TI , and VE at 40 RPM, FETCO2 at peak rpm and Phase 1 VE at all pedaling cadences. Comparisons between hip and xiphoid conditions indicate good ES values only for FETCO2 at 40 rpm and for Phase 1 VE at 40, 50 and peak rpm, respectively. In the healthy control group, moderate to high ES coefficients were noted for VE , VT /TI and Phase 1 VE when comparing calf and hip only at 40 rpm. Calf and xiphoid comparisons showed moderate

Fig. 2. Tidal volume and end tidal CO2 . A) Mean values for tidal volume as a function of minute ventilation (VE ) at different pedaling cadences (40, 50, 60 and peak rpm) reached by all participants for the 3 immersion levels; B) Mean percent fraction of expired end tidal CO2 (FETCO2 ) as a function of VE at different pedaling cadences (40, 50, 60 and peak rpm) reached by all participants for the 3 immersion levels. * p ≤ 0.05 significant difference between both groups at 40 and 50 rpm; ** p ≤ 0.05 significant difference between both groups at 50 and 60 rpm.

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Table 4 Fast ventilatory response (Phase 1 VE ) during exercise at different levels of water immersion and pedaling cadences on a water stationary bike. VARIABLES

PHASE 1 C PHASE 1 H PHASE 1 X PHASE 1 C PHASE 1 H PHASE 1 X

40 rpm

50 rpm

Healthy

HD

p

ES

Healthy

HD

p

ES

4.23 ± 4.33* 1.64 ± 2.66 2.76 ± 4.33 60 rpm 3.51 ± 5.20 2.27 ± 3.12 1.06 ± 4.94

3.95 ± 3.39*† 3.22 ± 3.30* 1.56 ± 2.39*

0.154 0.219 0.242

0.0 0.5 0.3

2.01 ± 2.24† 1.17 ± 3.09 −0.06 ± 2.55

0.992 0.823 0.314

0.3 0.0 0.6

2.48 ± 3.24‡ 0.15 ± 1.97 0.65 ± 3.06

0.413 0.090 0.482

0.2 0.8 0.1

1.15 ± 2.05 1.51 ± 3.50 1.83 ± 2.78 Peak rpm 3.72 ± 4.69 3.84 ± 2.25 1.67 ± 3.80

3.18 ± 4.41 1.87 ± 3.42 0.61 ± 2.13

0.957 0.364 0.064

0.1 0.5 0.4

Mean ± SD. Heart disease: HD; Effect sizes: ES where low effect = 0.2, moderate effect = 0.5, high effect = 0.8; Within group differences (p ≤ 0.05): *40 vs 50 rpm; †Calf vs Xiphoid; ‡Calf vs Hip. Calf immersion: C; Hip immersion: H; Xiphoid immersion: X. p and ES in table represents between group differences (p ≤ 0.05).

to high ES for TI /TTOT , VE and VT /TI at 40 rpm, VE and VT /TI at 50 RPM, TI /TTOT and Phase 1 at 60 rpm, and VE , VT /TI and Phase 1 VE at peak rpm. Finally, for hip and xiphoid comparisons, the same ES classification can be done for VE and VT /TI at 40 rpm, VE and VT /TI at 50 rpm, TI /TTOT and VT /TI at 60 rpm and VE , VT /TI and Phase 1 VE at peak rpm. Changes in ventilatory flow are shown in Fig. 1 as mean tidal volume (VT ) as a function of time for one breath cycle at different and immersion levels and exercise intensities. At submaximal levels of exercise the mean VT /TI rate was significantly greater in HD participants when compared to healthy participants. The difference was blunted at exercise intensities above 60 rpm. As shown in Fig. 1A (40 rpm) and 1 B (50 rpm), no significant difference was observed for VT /TI between all immersion levels for the HD group, while in the healthy group it was significantly lower at the xiphoid process level when compared to calf at 40 rpm (0.64± 0.168 vs 0.83± 0.288 L*s−1 , respectively, p = 0.019) and 50 rpm (0.87± 0.214 vs 1.03± 0.270 L*s−1 , respectively, p = 0.020). VT /TI was significantly higher at hip level when compared to calf (1.79± 0.319 vs 1.63± 0.398 L*s−1 , respectively, p = 0.037) for the HD group while no difference was observed between all immersion levels for the healthy group (Fig. 1C). Peak exercise (Fig. 1D) showed no significant differences between groups and immersion level. In the Healthy group where it was significantly lower at the xiphoid process level when compared to calf (1.97± 0.72 vs 2.40± 0.98 L*s−1 , respectively, p = 0.009). Fig. 2 illustrates both the VT and FETCO2 response to ventilation. Fig. 2A presents the mean values for tidal volume as a function of ventilation at different pedaling cadences (40, 50, 60 and peak rpm) that were attained by all participants for the 3 immersion levels. VT increased significantly as cadence increased in both groups. At peak exercise, the mean ventilation of all participants for the 3 immersion levels combined was approximately 65 Lmin−1 . At submaximal exercise levels (40 and 50 rpm), the HD group had a greater VE when compared to the healthy group (23.1 vs 18.4 L*min−1 , p=0.006 and 30.5 vs 25.7 L*min−1 , p=0.032, respectively) and this difference disappeared above 50 rpm until peak exercise for the 3 immersion levels combined. The fraction of expired end tidal CO2 (FETCO2 ) as a function of VE was not affected by either immersion level or pedaling cadence in both groups (Fig. 2B). There was, however, a significant difference at calf immersion between the HD and healthy groups at 50 rpm (4.99 ± 0.53 vs 5.45 ± 0.50%, p=0.016) and at 60 rpm (5.05 ± 0.60 vs 5.52 ± 0.53%, p=0.031) respectively. 3.2. Effect of immersion on fast ventilatory response during aquatic cycling exercise Fast respiratory (Phase 1 VE ) response was not significantly different between groups, independently of immersion level and pedaling cadence (Table 4). Nonetheless, effect size (ES) changes were observed. At calf immersion a low ES was observed at all

pedaling cadences while at hip and xiphoid immersion there were moderate to high ES at 40, 60 and peak rpm, and low to moderate ES at 40, 50 and peak rpm, respectively. Intragroup analysis showed that immersion had no significant effect on Phase 1 VE response in healthy participants. In contrast, immersion significantly affected Phase 1 VE response in the HD group. Specifically a significant effect of immersion was noticed at 40 and 50 rpm between calf vs xiphoid and 60 rpm for calf vs hips (Table 4). 4. Discussion Few studies have examined breathing pattern changes in cardiac patients exercising on a water stationary bicycle (WSB). Here we show that the participants suffering from heart disease (HD) exhibit acute breathing patterns that are significantly different from the Healthy group for distinct immersion levels (hips and xiphoid) and pedaling cadences. Specifically, the mean inspiratory flow rate (VT /TI ) was greater in the HD group (Fig. 2). This finding indicates that not only do HD participants have a compromised cardiocirculatory system, but also control of the respiratory system is somehow affected. 4.1. Breathing pattern comparisons In the current study, the hydrostatic column exerted on the immersed body appears to challenge control of breathing, thereby, modifying the breathing pattern. However, with immersion to the hip and xiphoid process the hydrostatic column exerted on the immersed body appears to challenge control of breathing, thereby, modifying the breathing pattern. During heavy exercise VE continuously rises until exhaustion (Fig. 2A), and the respiratory cycle shortens (respiratory frequency − RF) due to a reduction in both the expiratory time (TE ) and the inspiratory time (TI ) indicating that VT has reached its peak value (Fig. 1D). Even though participants may express diversity and individuality in their breathing patterns, when exercise causes an increased demand for VE , all participants tend to exhibit a more similar pattern, such as equal inspiratory and expiratory times (Benchetrit, 2000). A potential mechanism to explain this discrepancy between healthy and HD participants may be linked to what is observed with heart rate variability (HRV) in cardiac patients. In fact, it has been well described that HRV is affected by RF and in cardiac patients HRV has been shown to be significantly decreased, in comparison to non-cardiac patients (He et al., 2014). In the current study, an autonomic reduced plasticity may also extend to an attenuated capability of the HD group to adapt acutely to a changing environment (immersion level). As well, lower limb blood volume redistribution, independent of the immersed exercise modality (walking, running and cycling), is similar and entirely dependent on the depth of immersion, with the deepest being head out immersion (Christie et al., 1990; Garzon et al., 2015a,b,c). Thus, immersion causes a similar cephalad shift of blood volume independent of the exercise modality and the most

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plausible explanation for our observations is that the healthy group was able to easily adapt to immersion even at a low cadence while the HD group needed stronger stimuli to react. It seems that it was the increased exercise effort for the HD group, as seen exhibited by the breathing frequency at ≈ 33 b/min, which created the necessary stimulation to react similarly to the healthy group. 4.2. Effect of immersion in healthy and heart disease groups In the healthy group, immersed cycling at the xiphoid level appeared less strenuous as suggested by the significantly lower VT /TI and VE at submaximal pedaling cadences. In contrast, the HD group was not able to adapt and could only compensate by increasing the RF (Fig. 1A–C), suggesting that cycling at the xiphoid process requires a higher respiratory effort for the HD group, in comparison to the healthy group. A possible explanation is that the hydrostatic pressure may have contributed to at least two epiphenomena: 1) cephalad blood volume redistribution; and 2) compression of the abdominal wall pushing internal organs towards the diaphragm and compressing the lungs. The difference between healthy and HD groups at submaximal intensities (40–50 rpm, Table 2) could be due to heart congestion caused by cephalad blood volume redistribution, while abdominal wall compression affects both groups. On the other hand, at high-intensity exercise (50 to Peak rpm, Table 2) the healthy group continues to respond similarly as in submaximal intensities, while the HD group displays greater VE during xiphoid immersion when compared to calf immersion (dryland analog). Interestingly, xiphoid immersion at submaximal exercise intensities could imply that the HD group has a reduced plasticity to adapt. Nonetheless, the reduced plasticity may permit at submaximal exercise intensities a signal sensitivity to detect respiratory function anomalies due to the burden of blood volume redistribution. In the HD group, the effect of blood volume redistribution at near maximal intensity appears to blunt the respiratory system response (Fig. 2). In fact, at submaximal intensities, the respiratory system appears to be more sensitive and responsive, with differences between groups clearly discernable. However, when reaching exercise intensities near maximal, the difference between groups is abolished (Fig. 2A). Additionally, the blunting of the respiratory system response is also visible in Fig. 2B, where the end-tidal CO2 in the HD group is lower at all levels of immersion and exercise intensities when compared to the healthy group, even though the response profile is similar in both groups. In fact, previous studies with healthy participants exercising on a WSB showed either a significantly lower VE (Dressendorfer et al., 1976) or no difference between immersion and dryland (Brechat et al., 1999, 2013; Sheldahl et al., 1987, 1984). The discrepancy in the observations can be explained by small sample size, by different bike type and/or immersion level. Thus, our data strongly suggest that HD participants may be more sensitive to chest wall (xiphoid) immersion cycling. 4.3. Rapid ventilatory response (Phase 1 VE ) Immersion seems to act by reducing the inertial load, caused by the increase in cadence, leading to attenuation at the 10-s mark. The increase of the time constant of the ventilatory response, observed in response to cadence change immersed at the xiphoid process, could be due to the added pedaling workload caused by the higher water column height (at the same cadence) compared to calf immersion. This could account for the attenuation of phase 1 VE during xiphoid immersion demonstrating a slower drive relating to this type of work intensity, in comparison to the speed only increase that is observed at the calf level. Although the central command may be similar, the actual movement is perhaps hastened by

the water column height acting on leg movement inertia, resulting in lower afferent feedback. Another aspect affecting the fast drive to breathe while exercising can be the expiratory reserve volume (ERV) (Yamashiro and Kato, 2014). Indeed, the change in ERV during supine exercise is small (Henke et al., 1988) and correlates with a smaller phase 1 VE response component (Weiler-Ravell et al., 1983) when compared to the upright response on dryland. It has been previously reported that immersion at the level of the xiphoid process corresponds to a displacement of blood equivalent to moving from a standing position to a supine position on dryland (Risch, 1978), causing a reduction of the inspiratory capacity and the ERV. This ERV effect may therefore also contribute to the observed decrease in the phase 1 VE response during xiphoid immersion. Furthermore, the fast drive to breathe during exercise is influenced by the expiratory muscle control since ERV’s effect on VT is mediated by the expiratory muscles. However, the influence of hydrostatic pressure on lung volumes depends on the individual strength and compliance of the chest muscles, which in turn can influence the degree of displacement of the diaphragm by the water pressure causing the reduction of the total lung volume (Demura et al., 2006) that are also associated with the reduction of ERV. 4.4. Clinical implications In the current study during calf immersion (dryland analog) minimal differences were observed between groups in terms of respiratory system response. This also holds true for near maximal exercise intensities. At xiphoid immersion, however, submaximal exercise intensities led to increased detection sensitivity of potential respiratory system response anomalies (moderate to high ES). Thus, submaximal exercise (40–50 rpm) may be helpful for the clinical detection of blunted respiratory system responses in HD individuals. The detection of such anomalies could provide HD individuals with the extra incentive to adopt an exercise regimen and perhaps exercising on WSB could help restore the respiratory system response. From a clinical standpoint, ventilatory response (VE ) does not appear to limit exercise since VE peak (Fig. 2A) in both HD and HC are similar. This preliminary study indicates that patients with HD, screened for exercise according to the ACSM guidelines by their physician and under supervision, can safely exercise on a WSB at the immersion levels of hips or xiphoid process. Exercising on a WSB may make exercise more accessible to patients that are limited on dryland to exercise at an intensity that will help to improve both their cardiorespiratory and functional capacity. Lastly, exercising on a WSB may permit to better prescribe, control and individualise exercise intensity (Garzon et al., 2015a,b,c). 5. Conclusion Although exercising on a WSB immersed to the xiphoid process imposes a supplementary workload (∼15% greater than dryland analog calf immersion at 60 rpm (Garzon et al., 2015a,b,c; Leone et al., 2014), the only effect on the respiratory response to exercise was a reduction in the fast drive to breathe in the HD group. We can therefore conclude that this transient effect on the respiratory response to exercise would not be a contraindication for HD individuals to participate in this training modality. HD individuals, beyond cardiac compromised function, display also respiratory system response anomalies to exercise. Water immersion exercise at submaximal intensities may provide a means of detecting such anomalies. Thus, in the current study, acute water immersed exercise at submaximal intensities allowed the detection of blunted respiratory system responses in HD individuals. It is possible that

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this blunted response is reversible and may provide the clinician a new modality to detect and restore respiratory system response to exercise in HD individuals. 5.1. Limitations Despite the novel nature of this study, some limitations exist. First, the limited number of participants in both groups does not allow definitive conclusions to be drawn. Second, in the heart disease group only patients with documented coronary heart disease or congestive heart failure were included. Together with the limited number of participants and the composition of the heart disease group, the conclusions of this study should not be generalized to other cardiovascular diseases. Third, during the pedaling protocol, pedaling cadence controls exercise intensity. It is possible some participants were unable to increase cadence to sufficiently high levels, especially in the HD group, thereby limiting their performance and adding to data variability. The variability observed in our results might have been dictated by the severity of disease, gender, BMI, medication, peak aerobic capacity, muscle strength and function. It is likely that these variations reduced the capacity to detect clear differences between groups for the effect of immersion and pedaling cadence on ventilatory control. Nonetheless, we show that the differences with healthy participants are minimal. Thus, suggesting that WSB is a safe exercise modality for stable cardiac patients. This preliminary study requires further research with larger populations and better cardiac disease homogeneity, although patient recruitment might difficult the execution of the study. Acknowledgements The authors acknowledge all the participants for their voluntary involvement in the present study and wish to express extreme gratitude to Dr Serge Goulet who acted as medical consultant for the research. We would also like to thank the participants of Cœur Action Rive-sud, the direction of the sports center of the College Édouard Montpetit, and Athanasio Destounis for their collaboration. Thanks to V.J. Cadete for the scientific and editorial insight in the preparation of this manuscript. This study was supported by a CIHR (No 175918-MIA) grant. References ACSM (Ed.), 2006. ACSM’s Guidelines for Exercise Testing and Prescriptions. , 7 th edition ed. Lippincott Williams & Wilkins, Baltimore. Agostoni, P., et al., 2010. Effects of beta-blockers on ventilation efficiency in heart failure. Am. Heart J. 159 (6), 1067–1073. de Andrade, A.D., Junior, J.C., de Barros Melo, T.L., Rattes Lima, C.S., Brandao, D.C., de Melo Barcelar, J., 2016. Influence of different levels of immersion in water on the pulmonary function and respiratory muscle pressure in healthy individuals: observational study. Physiother. Res. Int., http://dx.doi.org/10. 1002/pri.1574. Benchetrit, G., 2000. Breathing pattern in humans: diversity and individuality. Respir. Physiol. 122 (2–3), 123–129. Brechat, P.H., Wolf, J.P., Simon-Rigaud, M.L., Brechat, N., Kantelip, J.P., Berthelay, S., Regnard, J., 1999. Influence of immersion on respiratory requirements during 30-min cycling exercise. Eur. Respir. J. 13 (4), 860–866. Brechat, P.H., Wolf, J.P., Simon-Rigaud, M.L., Brechat, N., Kantelip, J.P., Berthelay, S., Regnard, J., 2013. Hemodynamic requirements and thoracic fluid balance during and after 30 minutes immersed exercise:caution in immersion rehabilitation programmes. Sci. Sport 28 (1), 1–8. Chen, A.A., Kenny, G.P., Johnston, C.E., Giesbrecht, G.G., 1996. Design and evaluation of a modified underwater cycle ergometer. Can. J. Appl. Physiol. 21 (2), 134–148. Christie, J.L., Sheldahl, L.M., Tristani, F.E., Wann, L.S., Sagar, K.B., Levandoski, S.G., Morris, R.D., 1990. Cardiovascular regulation during head-out water immersion exercise. J. Appl. Physiol. 69 (2), 657–664. Connelly, T.P., Sheldahl, L.M., Tristani, F.E., Levandoski, S.G., Kalkhoff, R.K., Hoffman, M.D., Kalbfleisch, J.H., 1990. Effect of increased central blood volume

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