1. Harnessing the Therapeutic Power of Breathing
To Lower Blood Pressure & Reduce Stress
April 2006
Judy Chodirker, MHSc
Manager, Scientific Affairs

2. Agenda
 Overview
 Respiratory Pacing & the Physiological Mechanism of
Action
 Clinical Studies Highlights
 Professional Programs
 Questions? Feedback?
2

3. FDA-Cleared, Hypertension Treatment Device
 Clinically proven therapeutic breathing device
 Sustained blood pressure reductions within 8 weeks
 No side effects, no drug interactions
 Seven clinical trials published in peer-reviewed journals
 Relaxing, pleasant and easy to use
“We found that RESPeRATE was very helpful to many
of our patients who experience shallow breathing. And
patients, some of whom don’t have high blood
pressure, say it simply helps them relax. We use it for
patients to take home as a means of reinforcing our
biofeedback work with them.”
Leonard Schwartzburd, PhD
Clinical Psychologist & Director of the Clinical Institute of
Behavioral Medicine
Berkeley, California
3

4. RESPeRATE: FDA Indication for Use
RESPeRATE Indications for use (FDA k# 020399 OTC)
RESPeRATE Indications for use (FDA k# 020399 OTC)
The RESPeRATE is intended for use as a relaxation treatment for the
The RESPeRATE is intended for use as a relaxation treatment for the
reduction of stress by leading the user through interactively guided and
reduction of stress by leading the user through interactively guided and
monitored breathing exercises. The device is indicated for use only as
monitored breathing exercises. The device is indicated for use only as
an adjunctive treatment for high blood pressure, together with other
an adjunctive treatment for high blood pressure, together with other
pharmacological and/or non-pharmacological interventions.
pharmacological and/or non-pharmacological interventions.
 Specifically indicated for adjunctive treatment of hypertension &
reduction of stress
 Can be safely used with pharmacological and/or non-pharmacological
interventions
 Does not require a prescription
 Any changes in medication should be discussed with the doctor who
prescribed them
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5. World-Renowned Scientific Advisory Board
 Henry R. Black, M.D. – Executive Committee, American Heart
Association Council on High Blood Pressure Research
 Jay N. Cohn, M.D. – Founder Heart Failure Society of
America; Past President, American & International Societies of
Hypertension
 Joseph L. Izzo, MD. - Vice Chair Research, Department of
Medicine, University of Buffalo; Editorial Board, American
Journal of Hypertension (AJH) & Journal of Clinical
Hypertension (JCH).
 Ehud Grossman, M.D. – President, Israeli Society of
Hypertension; Editorial board, Journal of Human Hypertension .
 Giuseppe Mancia, M.D. - Past President, International &
European Society of Hypertension
 Thomas Pickering, M.D. – Past President, Society of
Behavioral Medicine; Past Secretary, American Society of
Hypertension; Author of Joint National Committee on
Hypertension (JNC VI).
 Michael Weber, M.D. – Immediate Past President, American
Society of Hypertension; Past editor of the American Journal of
Hypertension.
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6. RESPeRATE: Featured By Leading Medical &
General Publications
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7. Respiratory Pacing &
the Physiological Mechanism of Action

8. Paced Breathing is Traditionally Used For
Meditation and Healing
Its health benefits are taken for granted to be associated with
eliciting the “relaxation response”
Slow & deep Relaxation
breathing response
Health
Yoga, TM…
benefits
Evidence shows a direct effect
8

9. Therapeutic Possibilities (from literature)
THERAPEUTIC INTERACTIONS DISEASE AND AFFECTED SYSTEMS
Cardio CNS Pulmonary
Vascular
CNS
Heart Failure
Sleep Apnea
Paced Hypertension
Breathing Migraine
COPD
Cardiovascular Pulmonary
Asthma
Insomnia
Paced breathing modifies
multi-system disorders Panic Disorders
mainly via neural pathways Stress
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10. Therapeutic Breathing Pattern
Beneficial for Hypertension
Slow & deep breathing (<10 breaths/min)
Long exhalation
Without effort
On exhaling
• Sympathetic Outflow ↓
• Vagal Outflow ↑
• Baroreflex sensitivity ↑
• Chemoreflex sensitivity ↓
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11. Principle of Interactively Guided Breathing by the
RESPeRATE (RR) Device
Headphones – hear tones with which Computerized unit – detects inspiration &
user SYNCHRONIZES breathing expiration times and generates guiding
tones with slightly longer duration
Breathing pattern
modification
2 INhale EXhale
3 Breathing
IN & EX
1 Pacing tones
Respiration sensor – detects breathing
pattern via changes in belt tension
11

12. Typical RESPeRATE Session (from logged data)
13 “slow breathing minutes”
15 Longer exhalation
Respiration rate Effortless breathing
((breaths/min
10 Compliance
& performance
Expiration automatically stored
( time (sec
5
Inspiration
( time (sec Compliance = Total min.
spent in slow breathing
Performance = Measures
0
0 5 10 15 for quality of use
“Slow breathing” Minutes of exercise
(< 10 /min) 12

13. Interactive Respiratory-Pacing Technology
Headphones
RESPeRATE
15 minutes
analyzed your Few times a week
breathing and
composes
prolonged inhale
& exhale tones
RESPeRATE
computerized unit
Respiration Sensor
You synchronize your
breathing to
RESPeRATE
guiding tones
* Lowers BP up to 36/20 mmHg (top 10% reductions)
13
Average reductions for high BP 14/8 mmHg

14. Accumulated Effects of Paced Breathing
on the Cardiovascular System
1. Breathing rate ↓
2. Pulmonary stretch receptors activation ↑
3. Sympathetic outflow ↓
4. Microvascular tone ↓
5. Total peripheral resistance ↓
6. Blood Pressure ↓
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15. Respiratory Pacing Increases Capillary Blood
Flow (Reduces Vasoconstriction) & HRV
SPONTANEOUS GUIDED
Respiration rate 16-17 /min 5-6 /min
Respiration
signal
PP Increased
(mmHg) Heart Rate
Variability
HR
(bpm)
Increased
Capillary
Capillary Flow
Blood Flow
Time (sec) Time (sec)
Parati G, Gavish B, Izzo JL, Hypertension Primer (2003) 15

16. Clinical Studies Highlights

17. Clinical Trials Highlights
 7 separate published clinical trials1-6 (over 280 patients), of which 4
were randomized, controlled 1,2,5
 Significant & sustained 14/8 mmHg average reduction for high blood
pressure, independent of both gender and medication status
 Greater reductions for older patients (18/8 mmHg for age>65)
 Found effective for Refractory Hypertension6 and Isolated Systolic
Hypertension5
 Significant and consistent results measured at the clinic 1-6, at home2-6
and with a 24-hour ambulatory blood pressure monitor3
 No observed side effects
[1] Schein M et al, J Human Hyperten 2001; 15(4): 271 – 278 (Data pooled from first two studies)
[2] Grossman E et al, J Human Hyperten 2001; 15(4): 263 - 269.
[3] Rosenthal T et al, Am J Hyperten 2001; 14(1): 74 - 76.
[4] Meles E et al, Am J Hyperten 2004; 17:370-74.
[5] Elliott et al J clinical Hypertension 2004; 6(10): 553-559.
[6] Reuven Viskoper et al, Am J 2003; Vol 16:484-487
[7] Parati et al, Hypertension Primer, 3rd edition, pp 118
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18. Patient Population
Tested in Medicated, Elderly & Difficult-to-Control Populations
Number of patients 286
% Males 55%
Age (average) 58±11
<40 3%
Age in Years (%) 40-60 57%
>60 40%
% Medicated 78%
1 med 34%
# of meds 2 med 36%
>3 meds 30%
Systolic BP (mmHg) 150±13
Diastolic BP (mmHg) 90±9
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19. Study Designs
All included the same 8-week daily treatment with RESPeRATE
Study Treatment Control Comments
1 RR Walkman +6 m no treat
2 RR Walkman +6 m no treat
3 RR +BPM Walkman +BPM
POOLED 4 RR + BPM - 24ABPM
DATA
5 RR + BPM BPM +6 m with treat
6 RR +BPM BPM
7 RR +BPM -
8 RR -
Korean study
9 RR +usual care ** Usual care**
Hyp. Diabetics
Double blind and randomized
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20. Significant Blood Pressure Reductions
Treatment Control
Sys Dia Sys Dia
0  Pooled from 7 studies
- 13.7 -8.4 - 8.9 - 4.1
-4  Significant BP reduction
BP vs. control.
change
(mmHg) -8  Independent of gender
or medication
-12 P=0.002
 Greater response
P=0.008 in patients age >65 y
-16 -18/-8 vs -8/-3 mmHg
 No side effects
Elliott et al ESH 2004
Uncontrolled: Sys >140, n=129; Dia >90, n=83
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21. BP Controlled in 46% Patients of Stage 1 &
28% of Stage 2 Who Used RR
)Compared to Control: 4% of Stage 2 (p<0.005) and 34% of Stage 1 (p<0.05
Before After 8 weeks
180 180
Stage 2 Stage 2
(Systolic BP (mmHg
(Systolic BP (mmHg
160 160
Stage 1 Stage 1
140 140
Pre-HTN Pre-HTN
120 120
Normal Normal
100 100
50 60 70 80 90 100 110 50 60 70 80 90 100 110
(Diastolic BP (mmHg (Diastolic BP (mmHg
)Each point represents an individual RR patient (n= 211 21

22. Benefit Maintained (Month 2 to Month 6) in
Compliant Patients
Slow breathing
Office BP in mmHg
minutes per week
150 95 80
SBP DBP
Requested
45 or more
60
140 90
40
130 85
20
120 80 0
0 2 4 6
2 4 6
# months Treatment month
N=13, mean ± SE
Meles E et al. Data on file
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23. RR Eliminated Most of the “White Coat Effect”
P=0.002 P=0.02
30
Treatment Control 20
Treatment Control
15
( g H mm
20% ↓ 40% ↓
(
20 81%↓ 75%↓
( g H mm
(
10
10
5
P B cil ot s∆i D
P Bcil ot∆ y S
a
s
0 0
Base End Base End Base End Base End
For office SBP>140 mmHg and home SBP<135 mmHg
For office DBP> 90 mmHg and home DBP< 85 mmHg
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Elliott et al. Am J Hyperten, 2005, 18(5): 211A. Baseline & end home BP are averaged over 10

24. All-Day Sustained High BP Reductions
24h ABPM Monitoring
Significant 24-hour reduction within 8 weeks of 15 min.
RESPeRATE daily treatment
150
145 Before treatment
140
Systolic 135
BP
130
(mmHg)
125
120 After 8 wks 15 min
115 daily treatment
110
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
N=14; p<0.001
Hour
* Am J Hyperten 2001; 14(1): 74 – 76
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25. Bulk of Reduction Within 3-4 Weeks
0%
Control
25%
Home Systolic
BP change 50%
(% of 8 wk
reduction)
75%
100%
0 1 2 3 4 5 6 7 8
N=66; p<0.001 Treatment week
* Meles E et al, Am J Hyperten 2004; 17:370-74.
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26. Dose Response Relationship: Slow Breathing
Time vs. SBP Reduction
Non (Change in Systolic BP (mmHg 0 Extensive
use N=121 use
Minimum p<0.01
3.8 - requested 16.8 -
5- 45 min/wk
mmHg mmHg
p<0.001
10-
15-
20-
0 25 50 75 100 125
(Average Slow Breathing time per week (minute
* Elliott et al J clinical Hypertension June 2004 26

27. Response to Treatment Increases With Age
0
-5
BP change -2.2
(mmHg) -5.0
-10 -6.6
- 8.5
-11.4
-15
P<0.02 SBP
for SBP -16.1
DBP
-20
35-50 51-65 66-80
AGE (year)
Elliott et al ESH 2004
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28. Demonstration

29. What RR Can Tell About Its Use?
Feedback on breathing rate and compliance
To user
Displays
compliance upon
turning ON
# slow breathing
minutes done in
last 7 days
Displays
compliance &
performance - Goal: at
Press STAT least 45 min.
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30. Client’s Role in “Treatment with
RESPeRATE”?
 15-min daily session
 Quiet room, no other activities
 Record displayed “compliance” in a diary * (optional)
 Monitor morning BP and record in a diary (optional)
 Follow-up visits with healthcare professional as requested
* The displayed compliance is very important for motivating
the patient and to give a feeling of control/ self-empowerment.
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31. RESPeRATE User Survey (2006)
Performed in partnership with Ipsos- Vantis
 Good compliance: 90% use on regular basis, 73% >2x/week
(8-12 weeks from purchase)
 Improved BP: 85% reported RESPeRATE improved their BP
 Improved Sense of Well-being: 85% reported RESPeRATE
had a positive impact on their general well being
 Easy to Use: 95% reported RESPeRATE was easy to use or
took just a few sessions to learn
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32. RESPeRATE Professional Programs
3 Programs to Suit Your Practice Needs:
 Professional Dispensing Program  Take Control Sample Program
 Value-added service for your clients.  Provides you with free* Sample
 Enables you to dispense RR directly from your Certificates to enable your patients to
clinic. experience RESPeRATE first-hand.
 Use RR in your clinic, loan or sell to clients.  8-week trial period for enrolled patient
 Fair compensation for your time – fully with option to purchase at end of trial
controlled by you.  All shipping, billing and handling is looked
 Recover initial cost of device within 2-3 clients after directly by InterCure (the developer
 of RESPeRATE).
RR accessories available to facilitate sharing
of device
* Not including shipping & handling charge of
 Professional Coupon Program (NEW!) $39.95
– pass on a $50 discount to your patients
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33. Questions and Feedback
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34. “He Who Controls Breathing,
Controls Health”
Old Proverb
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35. Additional
Physiological overview
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36. Paced Breathing Inhibits Sympathetic Outflow Via
Increased Lung Inflation
* Chemoreflex VOLUME SIGNAL
excluded
CNS
Cardiac Cardiac
Stretch Output
PHASIC Receptors Brain Stem Sympath. BLOOD
LUNG Signal nervous PRESSURE
VOLUME Processor Outflow
Pulmonary Systemic
CHANGE Stretch Vascular
Receptors Resistance
Sensory Arterial PRESSURE SIGNAL
Inputs Baroreflex
Modified from Parati G, Gavish B, Izzo JL, Hypertension Primer (2003)
36

37. RESPeRATE vs. Metronome
RESPeRATE elicits greater modulation of Heart Rate and pulsatile
microvessel blood volume during exercise + vasodilatation effect post
exercise
Baseline ( Slow Breathing (6bpm Post Exercise
110
( HR (bpm
RESPeRATE
90
70
Metronome
50
Increased HR
) % ( Change
Blood Volume
Skin Pulsatile
225 modulation RESPeRATE
175 Metronome
125 Metronome
75 RESPeRATE
Increased
25 Vasodilatation
0 0.2 0.4 0.6 0.8 1 6.8 7.3 7.8 8.3 8.8 13 13.5 14 14.5 15
( Exercise Time (min
37

38. BP Reductions & Vasodilatation via Respiratory-
Pacing
Respiratory-Pacing; 15 min daily sessions
Spontaneous Respiration Paced Respiration
Decreases Sympathetic Outflow
Decreased TPR & Improved Baroreceptors Sensitivity
Regular 15 min. Conditioning Leads to Sustained BP Reductions
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