Physiology & Biochemistry 615
Essential Hypertension: Cardiovascular Response to Breath Hold Combined with Exercise
Authors
U. Hoffmann1*, P. Urban1*, J. Koschate1, U. Drescher1, R. Pfister2, G. Michels2
Affiliations
1
Key words ▶ apnea ● ▶ fitness-to-dive examination ● ▶ heart rate-pressure-product ● ▶ antihypertensive drugs ● ▶ diving response ●
Abstract
Institute of Physiology and Anatomy, German Sport University Cologne, Cologne, Germany Department III of Internal Medicine, Heart Centre of the University of Cologne, Cologne, Germany
Essential hypertension (EH) is a widespread disease and might be prevalent in apnea divers and master athletes. Little is known about the influence of EH and the antihypertensive drugs (AHD) on cardiovascular reactions to combined breath hold (BH) and exercise. In this pilot study, healthy divers (HCON) were compared with treated hypertensive divers with regard to heart rate (HR) and mean blood-pressure (MAP) responses to BH, exercise and the combination of both. Ten subjects with EH and ten healthy divers were tested. 3 different 20 s stimuli were applied: BH combined with 30 W or 150 W and 150 W without BH. The
time-charts during the stress intervals and during recovery were compared. Subjects treated with an angiotensin-converting enzyme (ACE) inhibitor showed higher changes for MAP values if breath hold was performed. HR responses were obviously changed if a β-blocker was part of the medication. One subject showed extreme MAP responses to all stimuli and conspicuous HR if BH was involved. The modulation of HR-/MAP-response in EH subjects depends on the mechanisms of antihypertensive agents. The combination of an ACE inhibitor and a β-blocker may give the best protection. It is recommended to include short apnea tests in the fitness-to-dive examination to individually predict potential endangerment.
List of Abbreviations
ΔRPPpeak
▼
▼ accepted after revision December 26, 2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1398627 Published online: April 14, 2015 Int J Sports Med 2015; 36: 615–623 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0172-4622 Correspondence Philip Urban, Uwe Hoffmann German Sport University Department of Physiology and Anatomy Am Sportpark Müngersdorf 6 Köln 50933 Germany Tel.: + 49/221/49822 910 Fax: + 49/221/49826 790 [email protected] [email protected]
ACE Subject group medicated with angiotensin converting enzyme inhibitor or an angiotensin-1-receptor blocker, or one of these two agents in combination with another agent, except a β-blocker AHD Anti-hypertensive drugs ARB Angiotensin-1-receptor blocker BB β-blocker BB-Comb Subject group medicated with combination of β-blockers and other AHD BB-Mono Subject group medicated with β-blockers BH Breath hold BH30 Breath-hold stimulus with 30 W work rate BH150 Breath-hold stimulus with simulta neous initiation of 150 W work rate BR Breathing rate ΔHR Changes in HR from 30 W reference ΔMAP Changes in MAP from 30 W reference Changes in RPP from 30 W reference at ΔRPP20 the end of the 20-s stimulus interval
aximum of changes in RPP from M 30 W reference within 30 s after the 20-s stimulus interval DBP Diastolic arterial blood pressure ECG Electrocardiogram FB150 stimulus with 150 W work rate with free breathing HCON Healthy control group HR Heart rate MAP Mean arterial blood pressure PAP Positive airway pressure RAAS Renin-angiotensin-aldosteronesystem RPP Rate pressure product SBP Systolic arterial blood pressure SC Single case subject SV Stroke volume TPR Total peripheral resistance WR Work rate Ventilation V’E %RPP 20 ΔRPP20 relative to RPP 30 W reference %RPPpeak ΔRPPpeak relative to RPP 30 W reference * Both authors contributed equally.
Hoffmann U et al. Essential hypertension: Cardiovascular Response … Int J Sports Med 2015; 36: 615–623
Downloaded by: Universite Laval. Copyrighted material.
2
616 Physiology & Biochemistry
▼
Voluntary episodes of apnea in combination with exercise, as during apnea diving, synchronized swimming or competitive swimming, provoke specific cardiovascular responses. Little or no information is available on the reactions of patients with cardiovascular regulative problems. Since apnea diving and master sports for elderly people have become more popular in recent years, it should be investigated whether or not episodes of apnea in combination with exercise may create critical regulative stress for hypertensive patients. Commonly, the physiological reactions to breath hold (BH) and immersion are summarized as ‘diving response’, marked by a decrease in heart rate (HR) and cardiac output (CO) [6, 37], an increase in mean arterial blood pressure (MAP) and total peripheral resistance (TPR) [1–4, 13, 14, 19–21, 37]. It is an accepted explanation that the reason for these reactions is an oxygen conserving effect [19] in the periphery to improve the oxygen delivery to brain, heart and other central organs. Apnea in combination with a simultaneous increase in work rate (WR) results in an initial rise of HR, followed by a decrease after approximately 10 s, accompanied by a continuous rise in MAP and TPR [4, 13, 14, 38]. Additionally, Hoffmann et al. [14] found increases in stroke volume (SV) in dry conditions, as well as Marongiu et al. [24], during free diving in the sea. Obviously, the combination of two controversial stresses for the cardio-vascular system, in this case exercise and breath hold, is an extremely demanding situation for MAP regulation. The wide range of people practicing apnea diving raises the question whether or not patients with arterial hypertension are endangered by the physiological reactions to breath hold. The prevalence of arterial hypertension appears to be around 30–45 % of the general population in Europe [23]. Hypertension is a risk factor for coronary artery disease and left ventricular hypertrophy (LVH), whereas LVH is an independent predictor of sudden cardiac death [8]. Coronary heart disease is the second most common cause of death in diving [25]. Hypertensive patients are allowed to dive if their systolic blood pressure can be adjusted to stable values at rest, below 140 mmHg and diastolic blood pressure below 90 mmHg, via antihypertensive medication [16]. The risk should be evaluated for every individual in sport and commercial diving. Bove [7] does not report any interaction with diving for ACE inhibitors and angiotensin receptor blockers, while the so called ‘cold intolerance’ caused by atenolol (a cardio-selective β-blocker) is relevant during diving. In international literature, like the guidelines for the management of arterial hypertension [23], no recommendations on apnea diving with hypertension are available.
In contrast to the effect of exercise stress on hypertensive patients, which was investigated under several aspects, usually as differences in maximal performance, but without on- and offkinetics in detail [12, 18, 31–33], little information about breathhold reactions of those patients is available. Only Finley et al. [9] investigated the effects of face immersion and breath hold when propranolol was given intravenously 1 h before the test in young healthy subjects. The duration of apnea was very short (8 s) and there were no on- and off-kinetics of MAP measured during the stimuli. Arnold et al. [5] tested the α-blocker Prazosin to avoid vasoconstriction during resting apnea in combination with face immersion. In this pilot study, healthy divers were compared with divers with treated hypertension regarding cardiovascular responses to breath hold, exercise and the combination of exercise and breath hold simultaneously. All subjects were experienced in breathhold situations. This investigation focused on the differences in HR and MAP responses to the combined exercise and breathhold stress between the 2 groups.
Methods
▼
Subjects
After a call for subjects in regional dive clubs, 38 divers with experience in breath-hold diving and/or SCUBA diving were included in the study. The diving experience was chosen to ensure the habituation to apneic situations. Eighteen volunteers had to be excluded due to other health problems, 10 divers with treated essential hypertension (8 males and 2 females), classified as high normal hypertension, were included and were compared with a control group of 10 healthy divers (8 males and 2 females – HCON). For anthropometric data and information ▶ Table 1. All hypertensive about physical activity refer to ● patients had received their anti-hypertensive drugs (AHD) for at least 3 years (mean value: 8,1 years). 6 different types of agents were used, as mono therapy or as combined therapy: β-blockers (Metoprolol, Bisoprolol), ACE inhibitors (Enalapril, Lisinopril, Ramipril), Angiotensin-1-receptor blockers (Lorsartan, Telmisartan, Olmesartan, Candesartan), Calcium-channel-blockers (Nitrendipin, Amlodipin), diuretic (Hydrochlorthiazid) and α-blocker (Clonidin). Therefore the following subgroups were investigated: β-blocker in mono therapy (BB-Mono, n = 2), β-blocker in combination with another agent of the ACE inhibitor group or a third agent (BB-Comb, n = 2), and ACE inhibitor or an angiotensin-1-receptor blocker, or one of these 2 agents in combination with another agent, except a β-blocker (ACE, n = 5). One female subject showed peculiar data and will be presented
Table 1 Number of subjects (with gender ratio), means ( ± SD) of anthropometric data, information about the duration between the experiment and the first diagnosis of arterial hypertension and information about physical activity.
n (gender ratio: m/f) Age [y] Weight [kg] Height [cm] BMI [kg · m − 2] Time since diagnosis hypertension [y] Physical training per week [min] SCUBA dives per year Subjects with regular apneic training/Underwater rugby player
HCON
BB-Mono
BB-Comb
ACE
SC
10 (8/2) 40.7 ± 1.7 83.3 ± 3.7 178.3 ± 1.9 26.3 ± 1.3 0 ± 0.0 249.0 ± 100.0 35.5 ± 42.6 6
2 (1/1) 36.5 ± 3.5 81 ± 27.0 177.5 ± 10.5 25 ± 5.6 13 ± 4.0 210.0 ± 127.3 40.0 ± 49.5 0
2 (2/0) 42.5 ± 12.5 99 ± 15 186 ± 7 28.4 ± 2.2 8.5 ± 1.5 105.0 ± 21.2 45.0 ± 7.1 1
5 (4/1) 43.6 ± 2.1 86.4 ± 5.7 180 ± 4.6 26.54 ± 0.7 6.2 ± 1.2 230.0 ± 97.5 23.0 ± 22.8 3
1 (0/1) 41 66 168 23.4 7 60 100 0
Hoffmann U et al. Essential hypertension: Cardiovascular Response … Int J Sports Med 2015; 36: 615–623
Downloaded by: Universite Laval. Copyrighted material.
Introduction
Physiology & Biochemistry 617
Experiment protocol
The subjects performed an exercise test on a cycle ergometer (Cardiac Stress Table, Lode, Groningen, the Netherlands) in semisupine position (45 °). The test was started with 20 s of breath hold to familiarize the subject with the breath-hold procedure. After 2 min of rest, the test started with a WR of 30 W. After a 4-min warm-up at 30 W, each subject performed 3 sets of 3 different stimuli (see example in ● ▶ Fig. 1): ▶ 20 s breath hold, with unchanged WR of 30 W (BH30), followed by 120 s of free breathing with a WR of 30 W as recovery period ▶ 20 s 150 W WR with free breathing (FB150), followed by 240 s of free breathing with a WR of 30 W as recovery period
PAP [hpa]
30 BH
15 0 BH
FB 15 0
0 15
30
0
SET 3
BH
BH
15
0 15
FB
10
SET 2
BH
0 15
FB
BH 30
SET 1
0
WR [W]
150 120 90 60 30 0 0
200
400
600
800 1000 1200 1400 1600 1 800 2 000 2200 Time [s]
Fig. 1 One example of a test protocol with 3 stimuli sets. Each set includes all 3 different stimuli (breath hold – BH30, 150 W work rate (WR) with free breathing – FB150, breath hold with simultaneous initiation of 150 W WR-BH150). For other subjects, the sets were randomized. The upper panel depicts the positive airway pressure (PAP) during the breathhold stimuli (BH30, BH150). The lower panel depicts the WR during the experiment, 30 W during warm up, BH30 and the recovery periods, 150 W during FB150 and BH150.
▶ 20 s breath hold with simultaneous initiation of 150 W WR (BH150), followed by 240 s of free breathing with a WR of 30 W as recovery period The sets were performed in randomized order for each subject. Before each breath hold the subjects were asked to take 2 deep but not maximal breaths, without hyperventilation, during a countdown of 10 s. With onset of breath hold, the spirometric tube was closed with a 0.5 mm aperture for 20 s. Subjects were asked to hold a constant positive airway pressure of 10 ± 2 hPa in their airways to prevent the closing of the glottis. The pressure was indicated to the subjects for self-control.
Measurements
For all tests a Task ForceTM Monitor (CNSystems, Austria) was used to measure the following parameters beat-to-beat: ▶ Continuous arterial blood pressure (CBP) by the photoplethysmographic method provided the MAP. ▶ HR from a 3-channel ECG. ▶ Intermittent oscillometric blood pressure to calibrate the finger cuff every 4 min. The ZAN680 Spirometric Unit (ZAN, Germany) was used to measure respiratory parameters. In this study only breath-bybreath ventilation (V’E) and breathing rate (BR) were evaluated. The subjects breathed through a mouthpiece and wore a nose clip during the whole experiment.
Data analysis
The data sets were synchronized and interpolated for 1- s intervals. Means of the 3 repetitions of the different stimuli were calculated for each subject. The average value of HR, MAP, breathing rate and ventilation for the interval − 40 s ≤ t ≤ − 20 s before stimulus was used as individual baseline as 30 W reference. For further analysis, the differences from the baseline were analyzed (ΔHR, ΔMAP, ΔBR, and ΔV’E). To estimate the myocardial oxygen demand, the rate-pressureproduct (RPP) was calculated as product of HR and SBP [17]. The steady states at 30 W reference were approximated as average for the interval − 40 s ≤ t ≤ − 20 s (RPP 30 W reference), RPP at the end of stimulus at t = 20 s (RPP20) and maxima of breath hold and recovery in the interval 0 s
Essential Hypertension: Cardiovascular Response to Breath Hold Combined with Exercise
Authors
U. Hoffmann1*, P. Urban1*, J. Koschate1, U. Drescher1, R. Pfister2, G. Michels2
Affiliations
1
Key words ▶ apnea ● ▶ fitness-to-dive examination ● ▶ heart rate-pressure-product ● ▶ antihypertensive drugs ● ▶ diving response ●
Abstract
Institute of Physiology and Anatomy, German Sport University Cologne, Cologne, Germany Department III of Internal Medicine, Heart Centre of the University of Cologne, Cologne, Germany
Essential hypertension (EH) is a widespread disease and might be prevalent in apnea divers and master athletes. Little is known about the influence of EH and the antihypertensive drugs (AHD) on cardiovascular reactions to combined breath hold (BH) and exercise. In this pilot study, healthy divers (HCON) were compared with treated hypertensive divers with regard to heart rate (HR) and mean blood-pressure (MAP) responses to BH, exercise and the combination of both. Ten subjects with EH and ten healthy divers were tested. 3 different 20 s stimuli were applied: BH combined with 30 W or 150 W and 150 W without BH. The
time-charts during the stress intervals and during recovery were compared. Subjects treated with an angiotensin-converting enzyme (ACE) inhibitor showed higher changes for MAP values if breath hold was performed. HR responses were obviously changed if a β-blocker was part of the medication. One subject showed extreme MAP responses to all stimuli and conspicuous HR if BH was involved. The modulation of HR-/MAP-response in EH subjects depends on the mechanisms of antihypertensive agents. The combination of an ACE inhibitor and a β-blocker may give the best protection. It is recommended to include short apnea tests in the fitness-to-dive examination to individually predict potential endangerment.
List of Abbreviations
ΔRPPpeak
▼
▼ accepted after revision December 26, 2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1398627 Published online: April 14, 2015 Int J Sports Med 2015; 36: 615–623 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0172-4622 Correspondence Philip Urban, Uwe Hoffmann German Sport University Department of Physiology and Anatomy Am Sportpark Müngersdorf 6 Köln 50933 Germany Tel.: + 49/221/49822 910 Fax: + 49/221/49826 790 [email protected] [email protected]
ACE Subject group medicated with angiotensin converting enzyme inhibitor or an angiotensin-1-receptor blocker, or one of these two agents in combination with another agent, except a β-blocker AHD Anti-hypertensive drugs ARB Angiotensin-1-receptor blocker BB β-blocker BB-Comb Subject group medicated with combination of β-blockers and other AHD BB-Mono Subject group medicated with β-blockers BH Breath hold BH30 Breath-hold stimulus with 30 W work rate BH150 Breath-hold stimulus with simulta neous initiation of 150 W work rate BR Breathing rate ΔHR Changes in HR from 30 W reference ΔMAP Changes in MAP from 30 W reference Changes in RPP from 30 W reference at ΔRPP20 the end of the 20-s stimulus interval
aximum of changes in RPP from M 30 W reference within 30 s after the 20-s stimulus interval DBP Diastolic arterial blood pressure ECG Electrocardiogram FB150 stimulus with 150 W work rate with free breathing HCON Healthy control group HR Heart rate MAP Mean arterial blood pressure PAP Positive airway pressure RAAS Renin-angiotensin-aldosteronesystem RPP Rate pressure product SBP Systolic arterial blood pressure SC Single case subject SV Stroke volume TPR Total peripheral resistance WR Work rate Ventilation V’E %RPP 20 ΔRPP20 relative to RPP 30 W reference %RPPpeak ΔRPPpeak relative to RPP 30 W reference * Both authors contributed equally.
Hoffmann U et al. Essential hypertension: Cardiovascular Response … Int J Sports Med 2015; 36: 615–623
Downloaded by: Universite Laval. Copyrighted material.
2
616 Physiology & Biochemistry
▼
Voluntary episodes of apnea in combination with exercise, as during apnea diving, synchronized swimming or competitive swimming, provoke specific cardiovascular responses. Little or no information is available on the reactions of patients with cardiovascular regulative problems. Since apnea diving and master sports for elderly people have become more popular in recent years, it should be investigated whether or not episodes of apnea in combination with exercise may create critical regulative stress for hypertensive patients. Commonly, the physiological reactions to breath hold (BH) and immersion are summarized as ‘diving response’, marked by a decrease in heart rate (HR) and cardiac output (CO) [6, 37], an increase in mean arterial blood pressure (MAP) and total peripheral resistance (TPR) [1–4, 13, 14, 19–21, 37]. It is an accepted explanation that the reason for these reactions is an oxygen conserving effect [19] in the periphery to improve the oxygen delivery to brain, heart and other central organs. Apnea in combination with a simultaneous increase in work rate (WR) results in an initial rise of HR, followed by a decrease after approximately 10 s, accompanied by a continuous rise in MAP and TPR [4, 13, 14, 38]. Additionally, Hoffmann et al. [14] found increases in stroke volume (SV) in dry conditions, as well as Marongiu et al. [24], during free diving in the sea. Obviously, the combination of two controversial stresses for the cardio-vascular system, in this case exercise and breath hold, is an extremely demanding situation for MAP regulation. The wide range of people practicing apnea diving raises the question whether or not patients with arterial hypertension are endangered by the physiological reactions to breath hold. The prevalence of arterial hypertension appears to be around 30–45 % of the general population in Europe [23]. Hypertension is a risk factor for coronary artery disease and left ventricular hypertrophy (LVH), whereas LVH is an independent predictor of sudden cardiac death [8]. Coronary heart disease is the second most common cause of death in diving [25]. Hypertensive patients are allowed to dive if their systolic blood pressure can be adjusted to stable values at rest, below 140 mmHg and diastolic blood pressure below 90 mmHg, via antihypertensive medication [16]. The risk should be evaluated for every individual in sport and commercial diving. Bove [7] does not report any interaction with diving for ACE inhibitors and angiotensin receptor blockers, while the so called ‘cold intolerance’ caused by atenolol (a cardio-selective β-blocker) is relevant during diving. In international literature, like the guidelines for the management of arterial hypertension [23], no recommendations on apnea diving with hypertension are available.
In contrast to the effect of exercise stress on hypertensive patients, which was investigated under several aspects, usually as differences in maximal performance, but without on- and offkinetics in detail [12, 18, 31–33], little information about breathhold reactions of those patients is available. Only Finley et al. [9] investigated the effects of face immersion and breath hold when propranolol was given intravenously 1 h before the test in young healthy subjects. The duration of apnea was very short (8 s) and there were no on- and off-kinetics of MAP measured during the stimuli. Arnold et al. [5] tested the α-blocker Prazosin to avoid vasoconstriction during resting apnea in combination with face immersion. In this pilot study, healthy divers were compared with divers with treated hypertension regarding cardiovascular responses to breath hold, exercise and the combination of exercise and breath hold simultaneously. All subjects were experienced in breathhold situations. This investigation focused on the differences in HR and MAP responses to the combined exercise and breathhold stress between the 2 groups.
Methods
▼
Subjects
After a call for subjects in regional dive clubs, 38 divers with experience in breath-hold diving and/or SCUBA diving were included in the study. The diving experience was chosen to ensure the habituation to apneic situations. Eighteen volunteers had to be excluded due to other health problems, 10 divers with treated essential hypertension (8 males and 2 females), classified as high normal hypertension, were included and were compared with a control group of 10 healthy divers (8 males and 2 females – HCON). For anthropometric data and information ▶ Table 1. All hypertensive about physical activity refer to ● patients had received their anti-hypertensive drugs (AHD) for at least 3 years (mean value: 8,1 years). 6 different types of agents were used, as mono therapy or as combined therapy: β-blockers (Metoprolol, Bisoprolol), ACE inhibitors (Enalapril, Lisinopril, Ramipril), Angiotensin-1-receptor blockers (Lorsartan, Telmisartan, Olmesartan, Candesartan), Calcium-channel-blockers (Nitrendipin, Amlodipin), diuretic (Hydrochlorthiazid) and α-blocker (Clonidin). Therefore the following subgroups were investigated: β-blocker in mono therapy (BB-Mono, n = 2), β-blocker in combination with another agent of the ACE inhibitor group or a third agent (BB-Comb, n = 2), and ACE inhibitor or an angiotensin-1-receptor blocker, or one of these 2 agents in combination with another agent, except a β-blocker (ACE, n = 5). One female subject showed peculiar data and will be presented
Table 1 Number of subjects (with gender ratio), means ( ± SD) of anthropometric data, information about the duration between the experiment and the first diagnosis of arterial hypertension and information about physical activity.
n (gender ratio: m/f) Age [y] Weight [kg] Height [cm] BMI [kg · m − 2] Time since diagnosis hypertension [y] Physical training per week [min] SCUBA dives per year Subjects with regular apneic training/Underwater rugby player
HCON
BB-Mono
BB-Comb
ACE
SC
10 (8/2) 40.7 ± 1.7 83.3 ± 3.7 178.3 ± 1.9 26.3 ± 1.3 0 ± 0.0 249.0 ± 100.0 35.5 ± 42.6 6
2 (1/1) 36.5 ± 3.5 81 ± 27.0 177.5 ± 10.5 25 ± 5.6 13 ± 4.0 210.0 ± 127.3 40.0 ± 49.5 0
2 (2/0) 42.5 ± 12.5 99 ± 15 186 ± 7 28.4 ± 2.2 8.5 ± 1.5 105.0 ± 21.2 45.0 ± 7.1 1
5 (4/1) 43.6 ± 2.1 86.4 ± 5.7 180 ± 4.6 26.54 ± 0.7 6.2 ± 1.2 230.0 ± 97.5 23.0 ± 22.8 3
1 (0/1) 41 66 168 23.4 7 60 100 0
Hoffmann U et al. Essential hypertension: Cardiovascular Response … Int J Sports Med 2015; 36: 615–623
Downloaded by: Universite Laval. Copyrighted material.
Introduction
Physiology & Biochemistry 617
Experiment protocol
The subjects performed an exercise test on a cycle ergometer (Cardiac Stress Table, Lode, Groningen, the Netherlands) in semisupine position (45 °). The test was started with 20 s of breath hold to familiarize the subject with the breath-hold procedure. After 2 min of rest, the test started with a WR of 30 W. After a 4-min warm-up at 30 W, each subject performed 3 sets of 3 different stimuli (see example in ● ▶ Fig. 1): ▶ 20 s breath hold, with unchanged WR of 30 W (BH30), followed by 120 s of free breathing with a WR of 30 W as recovery period ▶ 20 s 150 W WR with free breathing (FB150), followed by 240 s of free breathing with a WR of 30 W as recovery period
PAP [hpa]
30 BH
15 0 BH
FB 15 0
0 15
30
0
SET 3
BH
BH
15
0 15
FB
10
SET 2
BH
0 15
FB
BH 30
SET 1
0
WR [W]
150 120 90 60 30 0 0
200
400
600
800 1000 1200 1400 1600 1 800 2 000 2200 Time [s]
Fig. 1 One example of a test protocol with 3 stimuli sets. Each set includes all 3 different stimuli (breath hold – BH30, 150 W work rate (WR) with free breathing – FB150, breath hold with simultaneous initiation of 150 W WR-BH150). For other subjects, the sets were randomized. The upper panel depicts the positive airway pressure (PAP) during the breathhold stimuli (BH30, BH150). The lower panel depicts the WR during the experiment, 30 W during warm up, BH30 and the recovery periods, 150 W during FB150 and BH150.
▶ 20 s breath hold with simultaneous initiation of 150 W WR (BH150), followed by 240 s of free breathing with a WR of 30 W as recovery period The sets were performed in randomized order for each subject. Before each breath hold the subjects were asked to take 2 deep but not maximal breaths, without hyperventilation, during a countdown of 10 s. With onset of breath hold, the spirometric tube was closed with a 0.5 mm aperture for 20 s. Subjects were asked to hold a constant positive airway pressure of 10 ± 2 hPa in their airways to prevent the closing of the glottis. The pressure was indicated to the subjects for self-control.
Measurements
For all tests a Task ForceTM Monitor (CNSystems, Austria) was used to measure the following parameters beat-to-beat: ▶ Continuous arterial blood pressure (CBP) by the photoplethysmographic method provided the MAP. ▶ HR from a 3-channel ECG. ▶ Intermittent oscillometric blood pressure to calibrate the finger cuff every 4 min. The ZAN680 Spirometric Unit (ZAN, Germany) was used to measure respiratory parameters. In this study only breath-bybreath ventilation (V’E) and breathing rate (BR) were evaluated. The subjects breathed through a mouthpiece and wore a nose clip during the whole experiment.
Data analysis
The data sets were synchronized and interpolated for 1- s intervals. Means of the 3 repetitions of the different stimuli were calculated for each subject. The average value of HR, MAP, breathing rate and ventilation for the interval − 40 s ≤ t ≤ − 20 s before stimulus was used as individual baseline as 30 W reference. For further analysis, the differences from the baseline were analyzed (ΔHR, ΔMAP, ΔBR, and ΔV’E). To estimate the myocardial oxygen demand, the rate-pressureproduct (RPP) was calculated as product of HR and SBP [17]. The steady states at 30 W reference were approximated as average for the interval − 40 s ≤ t ≤ − 20 s (RPP 30 W reference), RPP at the end of stimulus at t = 20 s (RPP20) and maxima of breath hold and recovery in the interval 0 s
