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How does transdermal non-invasive CO2 infusion at the thumb cause improved blood circulation and cellular O2 levels in the foot?

How does transdermal non-invasive CO2 infusion at the thumb cause improved blood circulation and cellular O2 levels in the foot?

ABOUT THE AUTHOR

Judy Delp Ph.D.

Job Description

Professor of Biomedical Sciences

 

Education

B.S. Rockhurst University, Kansas City, Missouri

Ph.D. University of Missouri

 

Memberships

American Physiological Society

American Microcirculatory Society

American Heart Association

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. In the current study, treatment with transdermal CO2 in a localized area produced a sustained, remote vasodilation, and a lowering of systemic blood pressure.
 
These findings share some similarity with the hemodynamic changes that occur following an acute bout of exercise, in which both neural and vascular components contribute to a sustained decrease in vascular resistance and blood pressure that persists after cessation of exercise18. In the current study, the period of sustained vasodilation seen in response to transdermal CO2 was heightened in diabetic patients.
 
Interestingly, in hypertensive individuals, the period of post-exercise hypotension is of greater magnitude and duration as compared to that of normotensive individuals 18, 19. Paradoxically, the current findings in diabetic patients exposed to transdermal CO2 as well as previous findings in hypertensive patients post-exercise, imply that sensitivity to signals that mediate these cardiovascular responses increases in patients with pre-existing cardiovascular dysfunction19.
 
A sustained decrease in systolic blood pressure occurs post-exercise and here, following application of transdermal CO2, suggesting that neural mechanisms contribute to the observed reduction in systemic vascular resistance. The roles of efferent sympathetic nerve activity18-20, afferent nerve activity from muscle 21-24, and the baroreceptor reflex20, 23 in mediating post-exercise hypotension remain controversial.
 
Neural mechanism(s) could contribute to changes in skin SPP and systolic blood pressure induced by exposure to transdermal CO2. Future studies will need to monitor heart rate, heart rate variability, and sympathetic nerve activity during and after transdermal CO2 in order to more fully assess the role of the autonomic nervous system in mediating the sustained increases in SPP and systolic blood pressure reported in this initial study.
 
Vascular conductance increases in both active muscle and inactive vascular beds following a bout of dynamic exercise 25, 26, suggesting that circulating factors contribute to this period of sustained systemic vasodilation. Vasodilation occuring independently of neural regulation constitutes more than 50% of the increase in systemic vascular conductance that occurs post-exercise; however, the mechanisms that underlie the post-exercise vasodilation have remained elusive.
 
Studies that have employed blockade of nitric oxide or evaluation of circulating nitric oxide metabolites have shown that the post-exercise vasodilatory response does not rely on circulating nitric oxide availability27, 28. A recent study by New and colleagues28 indicates that the nadir of post-exercise hypotension coincides with the peak of appearance of lipid hydroperoxides in venous blood, suggesting that reactive oxygen species with known vasodilatory properties29-32 contribute to the exercise-induced decrease in systemic vascular resistance. In the current study, transdermal CO2 was applied to the thumb, and a significant increase in SPP was measured at the toe.
 
Thus, a similar circulating vasodilatory stimulus may contribute to the remote, sustained vasodilation created by local transdermal application of CO2. Further investigations will need to focus on the identification of the mechanisms involved in both the local and remote factors that contribute to the sustained hemodynamic changes produced by exposure of the skin to CO2.
 
Recently, studies have documented that episodes of brief, non-damaging ischemia occurring in a tissue can induce systemic protection against ischemia-reperfusion injury in a remote organ. This phenomenon, termed remote ischemic conditioning, has been demonstrated to confer protection against ischemic events in the myocardium33-35, brain36, and kidney37, 38.
 
Although shown to be effective in various clinical and pre-clinical models 34, 35, 38-40, the mechanism(s) of remote protection have not been clearly identified. Both neural and humoral mechanisms have been proposed to contribute to the protection against ischemic damage afforded by remote ischemic conditioning38, 39, 41-43.
 
Basalay et al.41 have shown that when remote ischemic conditioning is applied before induction of myocardial ischemia, sensory nerves and recruitment of a parasympathetic neural pathway are involved in reduction of infarct size. In contrast, application of remote ischemic conditioning after myocardial ischemia also afforded protection against infarction, but was not altered by vagotomy or peripheral denervation41.
 
Remote ischemic conditioning has also been demonstrated to improve perfusion of transplanted kidneys, suggesting that remote conditioning confers protection that does not rely on intact neural circuitry38. Recently, Michelsen and colleagues42 have demonstrated that dialysate of human plasma from subjects who underwent either ischemic preconditioning or exercise preconditioning reduced infarct size in rabbit hearts, indicating that release of a humoral factor, possibly acting on opioid receptors, contributes to the cardioprotective effects of ischemic and exercise preconditioning.
 
Other reports in the literature have also shown evidence of a humoral substances that mediate protection against ischemia when remote ischemic conditioning is applied; however, these substance(s) remain to be identified. Application of transdermal CO2 produces a remote vasodilation that may be mediated through release of a circulating humoral agent.
 
Future investigations will need to focus on assessment of plasma samples during and following transdermal CO2 application.
This pilot study demonstrated an increase in measures of remote skin microvascular function with D’OXYVA, a simple commercially-available device to deliver transdermal CO2. The effects of the treatment were evident at all periods up to and including the last test period, 240 minutes post-exposure.
 
Although the sample size was small in this study, a clear increase in SPP and SPP/SBP ratio and a decrease in SBP and DBP continued for 4 hours post-treatment. The differences in skin perfusion and blood pressure responses detected between diabetic and non-diabetic subjects will require further examination in larger studies.
 
Click below to access Prof. Judy Delp’s Presentation on Transdermal Delivery of Carbon Dioxide Boosts Microcirculation.
 
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HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

LEARN MORE ABOUT D'OXYVA
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Did you know when used in a regimen, D`OXYVA users have reported a number of health and beauty benefits?

doxyva benefits

OPTIMIZE BLOOD CIRCULATION FOR A WIDE VARIETY OF SIGNIFICANT OUTCOMES

D’OXYVA® (deoxyhemoglobin vasodilator) in various clinical trials has validated leading independent research results and demonstrated above-average results in improving a host of physiological functions at the same time.

People using D’OXYVA® have recorded significant improvements in cardiovascular activity leading to much improved physical activity. As part of a healthy lifestyle, D’OXYVA may help significantly reduce the risk of high blood pressure, hypertension, cholesterol, and diabetes in just two or three months, with an average use of 5 minutes a day and 5 times a week.

Poor circulation is a gateway for a litany of ailments: slow healing, depression, poor complexion, sores, slow metabolism, and more.

D’OXYVA significantly improves sustained oxygen-rich microcirculatory blood flow locally and throughout the body. Its patented method of fully non-invasive, painless, and harmless transdermal delivery is unique only to D’OXYVA.

When used daily, D’OXYVA users have reported a number of health and beauty benefits, including but not limited to:

  • Relief from symptoms of microvascular complications
  • Significantly increased cardiac function, physical fitness, endurance and strength, muscle size, body tone, faster recovery from sports injuries and surgical trauma
  • Improved self-esteem via promoting healthy and radiant skin, complexion, dry skin relief, and acne reduction
  • Significant reduction in downtime from other skin treatments and cosmetic procedures when used in combination, reduction in the appearance of scars, cellulite, fat, spider veins and stretch marks
  • Promoting and maintaining a healthy weight, improving general mobility, deeper, more restful sleep
  • Significant improvement of mental acuity; concentration, problem solving, multitasking, eye-hand coordination, heightened stamina, energy, and focus while managing stress
  • Improved vitals across the board during checkups with zero adverse event reports after years of regular use by people with various health, demographic, and ethnic backgrounds

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

LEARN MORE ABOUT D'OXYVA
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D’OXYVA as endorsed by Dr. Stephen Pfeifer

I was introduced several years ago to the transdermal CO2 D’OXYVA® delivery system and had the chance to utilize this modality in my practice as well as see the benefits noted by other clinicians who have started implementing the protocols. I was initially skeptical that such an affordable and simple system could have such profound health benefits. But after witnessing improvements in blood pressure, chronic venous insufficiency, diabetic wound healing, mood, and athletic performance enhancement, I realized that this treatment has the potential to help millions of patients with chronic health conditions. So, like most scientists, I began to investigate the reasons why this technology could be so effective.

Could it be possible that one of the main causes of most of our patients’ health problems is rooted in physiologic imbalances in the autonomic nervous system and microcirculation? Have we clinicians been chasing imperfect treatment options with medications and interventions that may certainly ameliorate symptoms initially, but which fail to address critical root causes of physiologic dysfunction and dysregulation?

There is an increasing consensus that microcirculation is critical in many ways. Our vascular system works in such a way that the great arteries have little impact on blood pressure, but small ones control almost 70% of the blood-flow resistance. Each adult organ can have more that 2 miles of capillaries inside it. Each capillary bed is in charge of exchanging small molecules between organ cells and the blood to maintain a healthy cell microenvironment or a state of homeostasis. The vascular system reacts to the concentration of metabolism’s by-products by deciding where to allocate resources and remove waste. However, with time and the accumulation of microcirculation damage due to bad health care habits, poor diet, and sickness, our bodies lose their ability to maintain homeostasis, resulting in poor wound healing, pain, infections, and so on. In other words, the microcirculation system helps our bodies maintain uninterrupted blood flow where it is needed the most.

Another overlooked system is the autonomic nervous system. Many books have been written in the functional medicine arena regarding the concept of adrenal exhaustion, as holistic doctors are realizing that this fundamental imbalance contributes to so many health conditions today. Today, we are bombarded with bad news on TV, we have work and financial challenges, and we have constant interruptions from our cell phones and emails. This constant attack on our survival cortisol hormones can be overwhelming. In functional medicine, we can even document this phenomenon with salivary cortisol hormone levels measured 4­–6 times per day. Typically, we see three progressive levels at play. The adrenal system starts as stressed and wired, then progresses to stressed and tired, followed by burned out and exhausted. At each level, this autonomic imbalance takes its toll on our health. Mother nature provided us with a wonderful adaptive capability to mount a stress response when, in the caveman days, we were running from a pack of wolves. It diverts all energy away from the parasympathetic system (rest and digestion) to a sympathetic response (fright and flight) so we can respond physically, using muscle strength, increased heart rate, and increased cardiac output to respond to a physical challenge. After the challenge is gone, the body should return to homeostasis and a calming parasympathetic mode for rest and digestion. Well, that is just not happening in today’s world, as we are in constant overdrive trying to escape the pack of wolves. So, we primary care doctors are always recommending stress-reduction strategies like yoga, better sleep hygiene, blood sugar stabilization diet strategies, and vitamin supplements that support adrenal balance.

It is refreshing to see a new technologic advancement that can help the many health problems exacerbated by autonomic imbalances. A simple and safe 5-minute transdermal CO2 delivery device has been shown to work immediately, and there is scientific proof that the physiologic effects continue for many hours. Scientific evidence is available that transdermal CO2 delivered by the D’OXYVA® device works through several mechanisms:

Reduces inflammation by reducing free radical plasma levels

Raises antioxidant levels and induces vasodilation (microcirculation) through humoral pathway communication

Decreased R-R heart rate interval variation

Activation of the PNS parasympathetic system, causing a vasodilation response

D’OXYVA® is a class 1 low-risk medical device using the natural properties of CO2 (a FDA-cleared drug) to activate our body’s chemoreceptors and increase organ blood flow through microcirculation while promoting oxygen delivery in capillary beds and organ tissue.

My name is Dr. Steve Pfeifer, and I am a consultant for Circularity and a retired functional medicine doctor. I am proud to be part of the Circularity scientific team that is partnering with clinicians to continue independent research regarding these benefits. More than two dozen research projects have been performed to test D’OXYVA® ‘s potential and safety, and much more are ongoing throughout the world. In fact, at the D’OXYVA® University here in Indianapolis, our doctors are studying the athletic enhancement potential in elite Indy Car race drivers and general athletes to document objective benefits with recovery and pulse oximeter readings reflecting perfusion indexes.

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An interview with key opinion leader Dr. Ito Puruhito

D’OXYVA® technology is a fast, reliable and effective approach for boosting circulation and promoting wellness for patients with diabetes and varicose veins. An interview with key opinion leader Dr. Ito Puruhito

Effective O2 and nutrient distribution from our lungs and guts to our organ tissues depends on micro-circulation. Microcirculation is where the vascular system allows the intravascular volume to interact with the extravascular space to deliver O2 and nutrients and in exchange pick up metabolic waste. When these physical processes are interrupted, our body becomes stressed.

Physiologic stress is useful and essential for our survival. For example, when we are sick it plays a crucial role in recruiting the immune cell protagonists to help us overcome infections and sickness. But when the stress transforms from a transitory state to a permanent state, our body loses the capacity to self-heal and achieves homeostasis over time. D’OXYVA® technology and its revolutionary CO2 transdermal delivery allow our body to regain proper micro-circulation blood flow to our organs.

One of the most common public health problems related with poor microcirculation is diabetic foot ulcers. Diabetic foot ulcers are a healthcare problem that affects more than 6.5 million patients in the USA alone. It is expected that 15% of this population are at risk of developing diabetic ulcers. Further epidemiological studies have identified that almost 25% of diabetic patients are at risk of lower extremity amputation and foot ulcers preceded 85% of all amputations.

Diabetic patients with concomitant foot ulcers represent a perpatient annual health-care cost that ranges between $12,000 and $17,000. Nationally the USA spends $13 billion in healthcare management of diabetic foot ulcers complication in addition to the expenses associated with diabetes itself.

To help our community to better understand the disease and the new proposed technology for improving diabetic patients’ quality of life, we interviewed Prof. Ito Puruhito, a world renowned cardio-thoracic surgeon based in Indonesia who has shared his knowledge at several top universities including Harvard. Prof. Puruhito has focused his research and efforts on better understanding micro-circulation, particularly in the wound healing process.

In our interview, Prof. Puruhito pointed out the importance of microcirculation health literacy among diabetic patients. He stated: “The better the circulation, the better the body can function in general. Micro-circulation delivers blood and oxygen directly to tissue, and when it is impaired, virtually every bodily function suffers.” Improving micro-circulation—especially in ulcers developed in diabetic patients—leads to improved treatment response, shorter healing time, and ulcer prevention. In other words, it will improve patient quality of life and may prevent extremity amputation.micro-circulation health literacy among diabetic patients. He stated: “The better the circulation, the better the body can function in general. Micro-circulation delivers blood and oxygen directly to tissue, and when it is impaired, virtually every bodily function suffers.” Improving micro-circulation—especially in ulcers developed in diabetic patients—leads to improved treatment response, shorter healing time, and ulcer prevention. In other words, it will improve patient quality of life and may prevent extremity amputation.

Prof. Puruhito has dedicated the last 50 years to researching how to improve microcirculation in his patients. During this time he tested several strategies andproducts intended to improve microcirculation and found D’OXYVA® technology to be the most efficient medical device.

Prof. Puruhito stated: “The D’OXYVA® technology caught my attention because of its remarkable ability to deliver such a high concentration of CO2 directly to the bloodstream.” He also said: “The ability to interact directly with dermal capillary and cellular receptors near the skin gives it the ability to produce the desired systemic effects, which is critical for improving micro-circulation and wound healing.”

Prof. Puruhito is part of the D’OXYVA® independent researcher team. He has been studying D’OXYVA®’s positive impact on his patients and has documented a remarkable success rate with difficult-to-treat wounds and diabetic ulcers. Also, his preliminary findings indicate clear improvements in health care indicators such as peripheral O2 concentration and perfusion indexes among his patients (scientific article pending for publication). Shortly after he recognized D’OXYVA® ’s healthcare benefits for general body health, he started to use D’OXYVA® on a daily basis and said: “As a researcher, it is one thing to observe results in your patients, but another to experience them in your body. With D’OXYVA® ’s transdermal technology, I had both!”

D’OXYVA® ’s consistent positive impact in improving microcirculation and health quality is leading to new treatment options for other pathologies such as varicose veins and cellulite, among others. We are confident that D’OXYVA® technology and effective transdermal delivery of CO2 will continue to prove its capacity to help the body improve its microcirculation and its capacity to self-heal and achieve homeostasis.

 

Bibliography

Chandan K. Sen, P. G. (2003, Nov–Dec). Human Skin Wounds: A Major and Snowballing Threat to Public Health and the Economy. Wound Repair Regen., 17(6), 763–771.

Doupis, K. A. (2012). Management of Diabetic foot ulcer . Diabetes Ther.

McCall, B. (2014, march 13). Medscape. Retrieved from Medscape/News & Perspective .

 

Special thanks to Prof. Puruhito for allowing us to perform the interview at the International Wound Care and Biotherapy Conference in Kuala Lumpur (2015). Dr. Ito Puruhito is a cardiothoracic surgeon with more than 50 years of experience and Professor of Surgery at Airlangga University Medical School in Surabaya, Indonesia. This article was published thanks to: “Circularity Healthcare” – D’OXYVA® , interviewer: Dr. Paul Kirkitelos.