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D`OXYVA
Heart
Arteries
Arterioles
Capillaries
Decreased
resistance
Smooth
muscle
cell
Interior
of arteriole
Arteriole
Smooth muscle cells
Smooth
muscle
relaxation
Normal
resting
tone
Increased
resistance
Smooth
muscle
contraction
Importance of Microcirculation
Recognition of importance of proper microcirculatory
function is growing rapidly, improved microcirculatory health
can support better outcomes in a wide variety of conditions,
both localized and systemic
Optimal microvascular function is critical in regulating blood
flow, tissue perfusion, blood pressure, oxygen delivery, waste
removal
Proper functioning has beneficial effects on prevention,
treatment of disease states; sepsis8, non-healing wounds,
diabetes9, hypertension10, 11, obesity12, metabolic syndrome13,
respiratory disorders, sexual dysfunction, and age-related
syndromes
Better, Faster
Healing
Increased
Metabolism
Pain Relief
Fatigue
Reduction
Better Sleep
Appetite
Targeting of Microcirculation
Studies suggest diabetics suffer most from macrovascular, microvascular
impairment, though there seems to be no limit
Microcirculation in chronic
venous insufficiency
The microcirculation as a
therapeutic target in the
treatment of sepsis
Microcirculation in obesity - an
unexplored domain
Microcirculation in skeletal muscle
Microvascular dysfunction in
obesity
Duling14 found an increase in perivascular PO2 and arteriolar diameter in hamster cheek pouch after
bathing the tissue in CO2
Hartmann et al. bathed lower extremities in CO2-enriched water and measured an increase in PO2 by
10%, while vasomotion by laser Doppler increased 300%. Some subjects had mild peripheral artery
disease. They concluded the Bohr effect resulted in better oxygen utility 15
In a subsequent investigation by the same authors using the same methods, they found an
improvement in dorsal foot TcPO2 and pain-free walking distance in claudicants
Savin et al.12 used administration methods similar to that described in a study with D'OXYVA in 10
subjects with peripheral artery disease and claudication. Femoral blood flow, tibial pressure, and
TcPO2 in the foot were significantly increased after skin exposure of CO2 gas
Fabry et al.16 randomized 62 patients to transdermal CO2 or room air for 18 consecutive days. In the
experimental group, there was an increase in great toe arterial pressure, a 20% increase in baseline
PO2, and improvements in vasomotion. These effects continued at 3- and 12-month follow-ups.
Toriyama et al.17 studied the effect of CO2 bathing in 83 limbs with critical ischemia and achieved limb
salvage in 83% without surgery. They concluded that peripheral vasodilation from CO2 bathing
resulted from an increased parasympathetic and decreased sympathetic activity.
The decreased binding to carbon dioxide in the blood due to increased oxygen
levels is known as the Haldane Effect.
It is important in the transport of carbon dioxide from the tissues to the lungs.
Vasamed SensiLase
Skin Perfusion Pressure
5 minutes pre-treatment
5 min post-treatment
30 minutes post-treatment
60 minutes post-treatment
120 minutes post-treatment
240 minutes post-treatment
50
*
40
30
20
10
-5 5
30
60
120
Time (minutes)
240
1. Neural Signals
Metaboreflex
2. Hormonal Signals
Epinephrine
Angiotensin
3. Tissue Signals
Adenosine
Potassium
}
Source: Prof. Judy M. Delp, PhD
Discussion
Rogers et.al., found transdermal CO2 with D`OXYVA in a localized area produced
a sustained, remote vasodilation, and a lowering of systemic blood pressure
Discussion (cont.)
Paradoxically, Rogers et.al. findings in diabetics and previous findings in
hypertensive patients post-exercise imply, sensitivity to signals mediating
cardiovascular responses increases in patients with pre-existing cardiovascular
dysfunction19
Sustained systolic blood pressure decrease occurs post-exercise and after CO2
delivery, suggesting neural mechanisms contribute to observed reduction in
systemic vascular resistance
Roles of efferent sympathetic nerve activity18-20, afferent nerve activity from
muscle21-24, baroreceptor reflex20, 23 in mediating post-exercise hypotension
remain controversial
Neural mechanism(s) could contribute to changes in skin SPP, systolic blood
pressure, induced by exposure to transdermal CO2 with D`OXYVA
Blood pressure
Heart and breathing rates
Body temperature
Digestion
Metabolism (thus affecting body weight)
The balance of water and electrolytes
(such as sodium and calcium)
The production of body fluids (saliva,
sweat, and tears)
Urination
Defecation
Sexual response
Randomized Trial
Penn State University, PA
The Effect of Transdermal CO2 Diffusion on Sympathetic Nerve Activity and Vascular
Responses in Humans
Phase I, randomized, placebo-controlled, double-blind human clinical trial on 13 healthy subjects
Principal Investigator: CHESTER A. RAY, PhD, Department of Medicine, The Heart &
Vascular Institute, College of Medicine, Pennsylvania State University, U.S.A.
Randomized Trial
Penn State University, PA
Data Collection:
General information
Effects:
Baseline
Vital sign
Heart Rate Variability (HRV)
ETCO2
0 min
5 min
TcPO2
D`OXYVA
5-min treatment
30 min
60 min
General Information
Male
Female
Total
10
13
Average
Min
Max
Age
32.512.7
23
60
height
1697.3
155
179
weight
65.910.1
47
80
Respiratory Results
(SpO2)
98
97.8
97.6
97.4
97.2
97
baseline
5 min
30 min
60 min
30 min
60 min
(ETCO2)
48
46
44
42
40
38
36
baseline
5 min
Heart Function
(Heart Rate)
R-R(RRIV)
100
300
90
250
200
80
150
70
100
60
50
50
0
baseline
5 min
30 min
60 min
baseline
5 min
NN(SDNN)
70
60
50
40
30
20
10
0
baseline
5 min
30 min
60 min
30 min
60 min
(VAG)
30
1.2
25
20
0.8
15
0.6
10
0.4
0.2
0
baseline
5 min
30 min
60 min
baseline
5 min
(Balance)
30
25
20
15
10
5
0
baseline
5 min
30 min
60 min
30 min
60 min
(ANS)
1.4
2.5
1.2
1
0.8
1.5
0.6
0.4
0.5
0.2
0
baseline
5 min
30 min
60 min
baseline
5 min
(ANS Age)
1.4
1.2
1
0.8
0.6
0.4
0.2
0
baseline
5 min
30 min
60 min
30 min
60 min
Discussion Summary
DOXYVAs SOLITION through skin pores and tissue without breaking skin barrier or
harming skin; detected no increase in blood or tissue CO2 during delivery and a
significant sustained O2 increase trending to 100% SpO2 in 10 minutes, and an
equally large decrease of CO2 in all subjects and in all studies.
Peripheral CO2 receptors in ANS sense increase concentration locally, signal nerve
activity.
Carbonic anhydrase, oxygen curve shift (Bohr effect), vasodilation detected in all
subjects for hours after delivery in all studies.
DOXYVA increases parasympathetic and decreases sympathetic nerve activity in
great majority of subjects for at least 60 minutes in a study.
DOXYVAs impact on microcirculation concurs with all published research in the
field explaining shunting that it increases microvascular blood flow and
vasomotor activity in areas deprived of it such as diabetic foot ulcers, ischemia,
vascular, burn and trauma wounds and decreases it where too much blood flow is
detrimental such as a cancerous tumor.
SenTec
Vasamed
Hitachi
Masimo
WeGene
Week 2
Week 3
1Wound
Background: WHO projects the largest increases in cardiovascular disease worldwide are occurring in
Asia. In the heart failure patients, the risk of death increasing particularly with left ventricular ejection
fraction (LVEF) less than 40%. There is resistance in practicing the implantation of defibrillator to reduce
sudden cardiac death among the Asian populations and there is less option could be taken to increase
the LVEF.
We are reporting a case of a 62 year-old gentleman, with history of four times angioplasty done for
vessels disease with poor LVEF (37%) and the first experience in Malaysia with deoxyhaemoglobin
vasodilator therapy in increasing the LVEF. After a month of therapy, our experience with dosage and
frequency of the transdermal carbon dioxide (CO2) delivery as well as patients LVEF before and after the
treatment were documented.
Results: After 4 weeks, the patient clinically improved from heart failure symptoms. Objectively, his LVEF
was increased from 37.17% to 46.99% and the PaO2 increased from 84.5mmHg to 104.7mmHg
Care and 2Cardiothoracic Surgical Unit, Hospital Raja Perempuan Zainab II, Malaysia
3Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, Malaysia
The iSpO2
Masimo
Personal
Health app
coupled
with your
iSpO2 pulse
oximeter
allows you
to track and
trend your
blood
saturation
(SpO2),
pulse rate
(PR), and
Perfusion
Index (PI).
Source: Masimo
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Email:
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Legal Disclaimer
Notice! Medical Carbon Dioxide is manufactured and delivered under applicable standards per each
country's regulatory requirements. In the United States, the Food and Drug Administration has cleared
the use of Medical Carbon Dioxide for the route of inhalation for humans but not yet for transdermal
delivery with D`OXYVA. Transportation of Medical Carbon Dioxide via any postal or courier service
requires certification for handling Dangerous Goods (HAZMAT) by the U.S. Department of Transportation
(DOT). Use of unapproved substances and products may be illegal, cause serious injury, and even death!
Warning! Ask your physician before using D`OXYVA FOR MEDICAL AND CLINICAL RESEARCH PURPOSES,
prescription only. The D`OXYVA transdermal delivery device holds a growing number of Class I (low risk)
licenses around the world. Use for non-medical purposes is available over-the-counter (OTC) and in
various retail stores online and offline. Circularity's novel D`OXYVA patented transdermal drug delivery
pathway with FDA-cleared Medical Carbon Dioxide (UN1013) has not been evaluated yet by the U.S.
Food and Drug Administration (FDA) and is not intended to diagnose, treat, cure, or prevent any disease.
The information provided herein is for educational and research purposes and is not intended to replace
medical advice.