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3 Reasons Why Most Wounds Won’t Heal

There are several connected causes for non-healing wounds.

According to figures from the U.S. Centers for Disease Control and Prevention, chronic wounds–injuries that have yet to heal after six weeks–affect some 5.7 American adults. There are many reasons for these non-healing wounds, and understanding each cause is vital to implementing the most effective wound care regimen possible.

Here are three of the more frequent explanations for why many wounds just won’t heal:

Poor circulation
As Johns Hopkins Medical School pointed out, blood is perhaps the most important component of the entire wound healing process. When an injury occurs, it’s the blood that transports cells to the wound site, which begin rebuilding veins and other important tissue structures. When you have poor circulation, blood cannot move around as quickly, and as a result, wounds take much longer to begin healing. According to Healthline, there are several medical conditions that cause poor circulation, including varicose veins, obesity and chronic ailments like diabetes, peripheral artery disease and Raynaud’s disease. Fortunately, there are just as many ways to improve circulation, like frequent exercise and elevating wounds or limbs in general.

Fluid buildup
According to the Mayo Clinic, edema occurs when fluid leaks from blood vessels, causing these secretions to accumulate in nearby tissue. The result is a large bump or nodule that is painful and sometimes prone to infection. Edema is usually the result of a number of medications, including several drug therapies geared toward diabetes. Edema can also occur due to a reaction to steroids, anti-inflammatory drugs and even estrogen supplements. Other than being uncomfortable, edema can wreak havoc on the wound-healing process. Due to fluid buildup, the blood vessels and tissue become rigid and immovable, greatly restricting blood flow. This compression cycle can also kill skin patches, which could lead to ulcers.
As a rule, infections can be quite traumatic to the host. Perhaps the biggest effect–one that might surprise some people–is that infections can all but halt the wound healing process. According to St. Luke’s Clinic, an average infection has a number of methods for preventing healthy tissue regeneration. For instance, some infections can extend the length of the inflammatory phase, and that can halt the subsequent stages of wound healing. Additionally, there are strains that can interfere with clotting mechanisms, which in turn causes wounds to continue bleeding. According to a 2010 study from the Journal of Dental Research, the two most damaging strains of bacteria are pseudomonas aeruginosa and staphylococcus.

When it comes to handling chronic wounds, patients need advanced wound care products to prevent infection and create a sustainable healing environment; that’s why so many patients turn to Advanced Tissue when they experience most chronic wounds. As the nation’s leader in the delivery of specialized wound care supplies, Advanced Tissue ships supplies to individuals at home and in long-term care facilities.

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Anesthesia, Microcirculation, and Wound Repair in Aging


Age-related changes in skin contribute to poor wound healing after surgical procedures. Changes in skin with age include a decline in thickness and composition, a decrease in the number of most cell types, and diminished microcirculation, the process that provides tissue perfusion, fluid homeostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause further disruption of the microvasculature of aged skin; however, perioperative management can be modified to minimize damage to aged tissues. Judicious use of fluids, maintenance of normal body temperature, pain control, and increased tissue oxygen tension are examples of adjustable variables that support microcirculation. Anesthetic agents influence microcirculation in a number of ways, including cardiac output, arterial pressure, and local microvascular changes. The authors examined the role of anesthetic management in optimizing microcirculation and potentially improving postoperative wound repair in older persons.

Aged skin is at increased risk of poor postoperative wound healing. Changes in the cutaneous microcirculation with aging contribute to this risk. This review examines the role of anesthesia management in microcirculatory function.

SURGICAL wound repair is a major problem in the older population, who are at increased risk of wound dehiscence and infection. As a specific example, surgical site infections (SSIs) are common (approximately 500,000 cases annually in the United States), lead to worse patient outcome (patients who develop SSI are twice as likely to die), and are an enormous economic burden (1–10 billion dollars annually). Many factors contribute to age-related changes in skin5 and subsequent vulnerability to impaired wound healing and infection. Changes in skin with age (fig. 1) include a decline in epidermal and dermal thickness and composition, as well as a decrease in the number of most resident cell types. The dermal–epidermal junction is flattened and the microcirculation is diminished. The latter is defined as blood flow through arterioles, capillaries, and venules and is the key system that affects the entire skin surface. In the aging patient, the microcirculation in the skin is reduced by 40% between the ages of 20 and 70 yr. The microcirculation provides tissue perfusion, fluid hemostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause disruption of the microcirculation in the skin as manifested by local edema resulting from vasodilation and increased vascular permeability.

Fig. 1.
Numerous changes in skin with age contribute to impaired wound healing.


Perioperative management can be modified to optimize the microcirculation. Measures that support the microcirculation include careful use of fluids, normothermia, pain control, and smoking cessation. Factors that can be influenced by intraoperative management (judicious use of fluids, maintenance of normal body temperature, pain control, and increased tissue oxygen tension) have been suggested to be beneficial as well. Most anesthetic agents also influence the microcirculation: a reduction in cardiac output and arterial pressure decreases flow in the microcirculation, whereas anesthetic-induced local microvascular changes and vasodilatation can increase perfusion. Optimization of these variables plays an important role in enhancing the microcirculation in all patients, but is especially relevant if modifications could improve postoperative wound healing in the older population.

In this review, we will use skin as a representative organ to describe age-related changes that negatively affect the microcirculation and have subsequent impacts on wound healing and the incidence of postoperative infection. We will then examine the role of anesthesia management in minimizing detrimental effects on the microcirculation. A greater understanding of these variables could promote improvements that lead to better outcomes with respect to wound repair in older patients.

Summary of Wound Repair and Aging

It has been nearly a century since it was noted that the rate of cutaneous scar formation after a wound is inversely related to the age of the patient. Four decades ago, it was observed that older age was associated with an increased risk of postoperative disruption of the surgical wound, leading to higher mortality. Recent data suggest that in patients older than 65 yr, development of SSI is associated with a two-fold increase in cost and a staggering four-fold increase in mortality.

Wound healing ensues via a sequential chain of events (with variable overlap) that includes inflammation, tissue formation, and remodeling (fig. 2). Circulating factors have a pivotal role in each of these phases. Accordingly, as we will discuss below, immediate changes in the microcirculation influence each stages of the wound-healing response in aging. As human data is lacking, we have taken data from established animal models of aging. Although animal models are not uniformly predictive of responses in human tissues, several animal models of wound healing are generally accepted.

Fig. 2.

The stages of wound healing are a sequential chain of events that include: (A) inflammation, (B) proliferation and granulation tissue formation, and (C) extracellular matrix (ECM) deposition and tissue remodeling. PDGF = platelet-derived growth factor; TGF-β1 = transforming growth factor-β1; TNF-α = tumor necrosis factor-α; VEGF = vascular endothelial growth factor.



Nearly every anesthesiologist who provides care to adults will participate in the care of geriatric patients. A growing older population is undergoing surgical procedures that are increasing in number and complexity. Poor healing of surgical wounds is a major cause of morbidity, mortality, and substantial economic burden. Wound healing is dependent on the microcirculation that supplies the incision area. Measures that support the microcirculation during the perioperative period have a profound effect on wound healing. Some measures such as maintenance of normal body temperature and control of postoperative pain are supported by ample evidence and have been implemented in routine clinical care. Other measures, for example, the choice of anesthesia technique and use of opioids are supported by basic research but need further clinical studies. A better understanding of the effect of aging and anesthesia on the microcirculation can potentially assist in improving postoperative wound repair, thereby benefiting a growing older population.


The Surgical Context of Wound Repair and Aging

Measures that support the microcirculation improve wound repair, thereby reducing the risk of postoperative dehiscence and infection.52General preoperative measures such as smoking cessation and optimal management of comorbid medical conditions have been reviewed in other contexts.53,54 For the purpose of this review, we will focus on interventions in the perioperative setting.

Oxygen Administration

Wound healing is dependent upon adequate levels of oxygen.55 Oxygen interacts with growth factor signaling and regulates numerous transduction pathways necessary for cell proliferation and migration.56 It is also an indispensable factor for oxidative killing of microbes.57 Consequently, the effects of oxygen tension on the outcome of surgical wounds have been best studied in the context of postoperative infection. Resistance to surgical wound infection is presumed to be oxygen dependent—with low oxygen tension viewed as a predictor of the development of infection,56 particularly when subcutaneous tissue oxygenation (measured by a polarographic electrode) decreases to less than 40 mmHg.58

In two recent meta-analyses, one found that perioperative supplemental oxygen therapy exerts a significant beneficial effect on the prevention of SSIs,59 whereas the other suggested a benefit only for specific subpopulations.60 Although most authors suggest that supplemental oxygen during surgery is associated with a reduction in infection risk,61,62 others propose it may be associated with an increased incidence of postoperative wound infection.63Notably, in the latter report, the sample size was small and there was a difference in the baseline characteristics of the groups. A prospective trial randomizing patients to either 30 or 80% supplemental oxygen during and 2 h after surgery did not find any difference in several outcome measures including death, pulmonary complications, and wound healing.64 Of note, the administration of oxygen to aged subjects may be limited by the finding that although arterial oxygen tension did not decrease with age, there was reduced steady-state transfer of carbon monoxide in the lungs.65 This indicates that oxygen transport could be diffusion-limited in older subjects, especially when oxygen consumption is increased. Furthermore, longitudinal studies of five healthy men over 3 decades showed impaired efficiency of maximal peripheral oxygen extraction,66 suggesting that tissue oxygen uptake is reduced in the aged subjects.67 This likely reflects a decrease in the number of capillaries as well as a reduction in mitochondrial enzyme activity.68 Animal models (rabbit69 and mouse69,70 ) have suggested that aging and ischemia have an additive effect on disruption of wound healing. Consequently, the potential benefit of increasing tissue oxygen tension during surgical wound repair in older patients should be further evaluated.




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D’OXYVA as endorsed by Dr. Stephen Pfeifer

I was introduced several years ago to the transdermal COD’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 COdelivery 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 COdelivered 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 CO(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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Peripheral Edema and D’OXYVA Transdermal Application as a Potential Treatment Option

Peripheral edema is the result/manifestation of many diseases, inflammation processes, and loss of body compensatory mechanism of chronic conditions, but the first pathophysiology disturbance is at the capillary level (microcirculation). D’OXYVA® transdermal COapplication has demonstrated to be beneficial to improve blood flow by decreasing microcirculation blood resistance and improving venous insufficiency. COis one of the few local humoral mediators with the potential to modulate blood flow in capillary beds. COenhances the following capillary bed functions:

– Arteriole elastic retractions and vasomotion that allows constant blood flow through the capillary bed.

– Reconstruct the role of adjacent closed capillaries.

– Promote vasodilation of the arterio-venous anastomosis without increased venous return.

Also, COis a natural anti-inflammatory agent that helps one’s circulatory system to perform better. CO2  especially helps one’s circulatory system by increasing venous blood return to the heart and systolic output by passive peripheral vasodilation, without increasing mean arterial blood pressure.
It is important that any patient who has edema needs to be followed/supervised by a physician because there is the need to assess critical organ functions and etiology of the disease, like BP, venous obstruction, low plasma protein concentration, or lymphatic obstruction among others.

Cellulite and carbon dioxide bath. (2009, May 9).

Dogaru gabriela, r. A. (2015). Therapeutic effects of carbonated mineral waters in cardiovascular rehabilitation . Balneo research journal, 36-39.

Maria vitória carmo penhaveli, v. H. (2013). Effects of carbon dioxide therapy on the healing of acute skin wounds induced on the back of rats1. Acta cirúrgica brasileira , 334-339.

Nouvong, j. S. (n.d.). Assessment of microcirculation and the prediction of healing in diabetic foot ulcers. Western University of Health Sciences, College of Podiatric Medicine United States of America:

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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 Oand 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 Oand 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 COdirectly 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 Oconcentration 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 COwill continue to prove its capacity to help the body improve its microcirculation and its capacity to self-heal and achieve homeostasis.



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.

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How does Poor Blood Circulation Affect your Skin?

We all know how a poor blood circulation can affect our state of health but do you also know that a poor blood circulation can adversely affect our state of skin too? Well, I sort of know but I didn’t really think too much of it until I was introduced to donkey skin gelatin for beauty as I learnt from my bestie that not only did her relative’s skin tone improved after taking the herbal mixture, but her pigmentation spots actually faded because the herbal mixture promote blood circulation and increase the reproduction of cells. Now, that got me thinking that perhaps some of my skin problems might be due to a poorer blood circulation.

What skin problems can a poor blood circulation cause?
I’m not going to cite any medical studies here but if you think about it, a better blood circulation will definitely increase the reproduction of cells, and this will benefit the skin too. So while a poor skin condition could be due to many reasons, a poor blood circulation is definitely going to show up as poor skin condition. Here, I’ll cover briefly on six skin problems that can result due to poor blood circulation.

1. Unflattering skin tone

When someone is anemic and has a poor blood circulation, chances are, that person has a pallid complexion. In some cases, the skin tone is also dull and may even look ashy.

2. Skin discoloration

Poor blood circulation often results in a lack of oxygen in the blood and hence, this can also cause skin pigmentation, dark spots or blotchy complexion.

3. Acne and problematic skin

Obviously, a poor blood circulation is going to affect how some of your major organs function and over time, these organs can become stressed and are unable to eliminate toxins properly. This can put more pressure on your lymphatic system and your lymph nodes can become sluggish with toxins building up and then excreted through the skin, causing acne or other problematic conditions such as dry skin, itchy skin or even skin rashes.

4. Slower scar healing

Those with acne and have poor blood circulation may find that their acne wounds take a longer time to heal because there is less efficient transport of good nutrients into the skin cells.

5. Wrinkle formation

As mentioned, if your blood cannot circulation well, there is less efficient transport of good nutrients into the skin cells, and this can adversely affect collagen production – thereby causing wrinkle formation.

6. Dark eye circle

While not all dark eye circles are a result of poor blood circulation but because the skin in the area around our eyes is quite thin, poor circulation results in less oxygenated blood, manifesting in a bluish/purplish appearance under the eyes called dark eye circles.

How to improve your blood circulation

Actually, I noticed that my skin has improved gradually over these few months. Yes, the products I’ve used would have helped but one of the improvements I noticed was that my undereye area is no longer so dark. I don’t need to use thick concealer and can make do with normal foundation. At first, I thought the eye cream I am using has helped but I doubted because external products don’t help my undereye area very much except for reducing the fine lines. Then I remembered that I’ve been taking Fit Solution for over six months now and that health supplement has definitely been improving my blood circulation. In addition, I noticed that my acne healing is much faster these days too.

1. Diet and health supplements

A balanced diet rich in vitamin B, C, D and E will be helpful. However, if you find that you are not getting sufficient sources from your food, try taking a vitamin supplement if that is a comfortable idea to you.

2. Exercise

I don’t exercise but it is a sure way to increase blood circulation. In fact, as soon as you start exercising, you’ll notice that your complexion might start looking rosier because of the increased blood circulation that shows up on the surface.

3. Massage

Due to the physical manipulation of soft tissue and also the chemicals released in our bodies as part of the relaxation response, massage increases the circulation of blood. Such an improved circulation can enhance the delivery of oxygen and nutrients to skin cells. So both body and facial massages are good to indulge in for a better blood flow.

I think someone who is healthy is likely going to have a better blood circulation than one who is not. So if you suspect that your blood circulation is causing your skin problems, perhaps it’s time to improve your diet or take time to exercise for the blood flow to circulate better.

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What is D’OXYVA?

The D’OXYVA® device is a simple, commercially- available device to deliver transdermal carbon dioxide (CO2). It consists of a patented and patent-pending ergonomic polymer shell that is propelled by a patented single-use mini steel pressurized cartridge (45 psi) filled with pharmaceutical-grade (99.5%) liquid, purified CO2. The mini-steel cylinder is GMP-compliant, and recyclable.

D’OXYVA was identified by the IRB in a human clinical trial as a non-significant risk (NSR) device.

The D’OXYVA device is manufactured in the United States and other countries. D’OXYVA is an ISO-complaint device, which means that Circularity Healthcare, LLC has received a certification to certify that D’OXYVA fulfills all of the international requirements for medical device regulations, like risk assessment and maintaining effective processes for safe design, manufacture and distribution.manufacture and distribution.


CO2 is the protagonist in D’OXYVA’s revolutionary approach to improving healthcare and patients’ quality of life. The medical device causes controlled ischemia-like stress in a local area of the body to promote central nervous system activity and circulate humoral agents that favor micro-circulation, especially at the organ capillary beds.

Adequate blood flow in the capillary bed is essential for tissue survival and optimal organ function. If blood passes too fast or does not pass at all, the tissue cannot extract O2 efficiently and will generate what is known as capillary dysfunction, which is related to chronic pain, poor wound healing, diabetic neuropathy and Alzheimer’s disease, among other conditions.


· It is a key player in regulating extracellular hydrogen concentrations and pH through various systems, like the respiratory system, kidneys and various buffers.

· Biochemistry: An increase or decrease in 1 mmHg pCO2 will cause a decrease or increase in pH of 0.08 units in acute patients. In chronic patients, a pCO2 change of 1 mmHg will cause a pH change of 0.03 units.

· The Bohr and Haldane effects determine the interaction of O2 and CO2. At the cellular level, pCO2 concentration causes Hb-O2 dissociation.
· It is attained by our body through inhalation.


· Increased pCO2 promotes arteriolar dilatation in various tissues, while a modest effect has been shown in skeletal muscle tissues.

· CO2 can be delivered into our body through the skin (transdermal).

It is used in the medical industry to:

· Rapidly increase the depth of anesthesia when volatile agents are being administered—it increases the depth of respiration and helps to overcome breath holding and bronchial spasm

· Facilitate blind intubation in anesthetic practice

· Facilitate vasodilation and thus lessen the degree of metabolic acidosis during the induction of hypothermia

· Increase cerebral blood flow in arteriosclerotic patients undergoing surgery

· Stimulate respiration after a period of apnea

· Prevent hypocapnia during hyperventilation

It is also used in:

· Clinical and physiological investigations

· Gynecological investigations for insufflation into the fallopian tubes and abdominal cavities

· Tissue-freezing techniques (as dry ice) and to destroy warts by freezing.

· The CO2 concentration increment potentiates the S-shaped hemoglobin (Hb) to O2 dissociation curve. It helps Hb to unload O2 from 40% O2 dissociation under normal conditions to 70% O2 dissociation under increase CO2 concentration.


Transdermal delivery of CO2 has proved to improve local microcirculation (capillary beds) blood flow and tissue perfusion, but it also positively improves systemic blood pressure and TcpO2 (most likely due to the Bohr effect). As mentioned before, therapeutic medical-grade CO2 is used for vasodilatation in the medical field for several conditions and procedures.

Local, CO2 therapy has shown great success rates to improve the healthcare of patients through:

· Treatment for diabetic foot

· Increased microcirculation blood flow and dissociated O2 in healthy and diabetic individuals

·Treatment for arterial stenosis obliterans

· Chronic wound healing

· Adipose tissue treatment

Systemically, CO2 therapy has shown great success to improve:

· The healthcare of patients with high blood pressure

· General vital organ function, like that of the: – Pancreas – Liver – Brain – Kidneys

We are currently finding clinical researchers who are interested in participating in clinical trials with our medical device. Our goal is to produce scientific evidence of D’OXYVA’s potential to improve healthcare.

More than two dozen research projects have been performed to test D’OXYVA potential and its capability to help patients obtain wellness. We have tested the efficiency, tolerability and safety of the D’OXYVA medical device in delivering a gentle, highly concentrated CO2 mist to the body through the skin and prove the reproducibility of its effects beyond doubt. To do so, we measured body CO2 concentration before and after treatment as well as the expected physiological response to CO2 treatment. In addition, we have partnered with healthcare leaders and clinicians to perform independent research studies.

Research end points:

1) Safety and tolerability  Up to date, no adverse side effects or negative healthcare responses have been recorded from our clients using D’OXYVA. Also, no participants in our research projects had any documented side effects from treatment. We encourage you to discuss with your healthcare professional if D’OXYVA medical device is right for you.

· Up to date, no adverse side effects or negative healthcare responses have been recorded from our clients using D’OXYVA. Also, no participants in our research projects had any documented side effects from treatment. We encourage you to discuss with your healthcare professional if D’OXYVA medical device is right for you.

· Measured transcutaneous carbon dioxide (TcPCO2)

· Within the first 5 minutes of D’OXYVA treatment, TcPCO2 increases in the body, followed by a decline slope that lasts approximately 240 minutes until returning to baseline values.

· In healthy individuals, D’OXYVA does not increase pCO2 beyond the body buffer’s manageable range, making it completely safe.

2) Efficiency CO2 delivery

a. Measured blood perfusion index (PI)
· The results of each research project consistently showed a significant increment on PI in 100% of participants within the first 5 minutes of treatment, peaking at 60 minutes after treatment. From 60 minutes after treatment until 240 minutes (our largest time period evaluated after treatment), PI decreased slowly to baseline levels. PI studies on diabetic patients has demonstrated a greater response to CO2 that in non-diabetic healthy individuals. Our studies have recorded that the PI change (from baseline) in diabetic patients was double the PI change recorded in healthy patients (Graph 1).
Graph 1: Skin perfusion index (SPP) in healthy and diabetic participants vs. time after using the D’OXYVA medical device

b. O2 concentration
 D’OXYVA has consistently reported increased free O2 molecules in our patients’ blood streams. The effective transdermal CO2 delivery allows the body to increment O2 availability through the Bohr effect, which helps hemoglobin cells to unload O2 more easily by decreasing its affinity.

c. Blood pressure
All of the research projects performed up to date have consistently recorded a significant decrease in systolic blood pressure (from the heart) and diastolic (return to the heart) blood pressure. These results have been consistent throughout all study time periods up to 240 minutes (our longest time period evaluated after treatment).

d. Diabetic ulcer
A research project focusing on D’OXYVA’s impact on diabetic ulcers recorded significant changes in wound healing, like significant granulation of tissue and improved ulcer borders, as soon as 1 week into the D’OXYVA treatment plan (Image 1).

e. Sports
Amateur and professional athletes are always searching for ways to improve cardiovascular function and increase the vascular transport capacity of skeletal muscle. Better vascular transport capacity translates to more O2 and nutrients delivered to our muscles, which means better performance in the field.
D’OXYVA research focusing on the perfusion index (PI) of superficial skeletal muscles has recorded excellent results. The most important findings demonstrate that participants who use D’OXYVA doubled their PI in comparison to the control group.

f. Blood alkalinity
Use of D’OXYVA has consistently been shown to improve local cellular homeostasis. It has the potential to improve body pH values by promoting an alkaline ambiance. A slightly alkaline microenvironment After 7 days of treatment with D’OXYVA (1x per day) – same wound dressing as before within the body promotes good health and optimal body organ performance.


The SENTEC digital monitor system has confirmed successful and constant CO2 transdermal delivery to the skin capillary bed after a 5-minute period of exposure to highly concentrated CO2 vapor produced by D’OXYVA.
The perceived healthcare benefits occur almost instantly, with local microcirculation improvements followed by an increment of SPO2 that last up to 240 minutes.

Nonetheless, adherence to a D’OXYVA regiment has demonstrated benefits to individuals suffering from difficult-to-heal skin wounds like diabetic ulcers, who demonstrated significant clinical improvements after two weeks of D’OXYVA.
Patients who achieved D’OXYVA device adherence for more than a month have shown wellness that persists in clinical trials.

Why can the D’OXYVA medical device and its capacity to produce highly concentrated CO2 vapor improve general health care? Judy M. Delp, Ph.D. in physiology and professor at the Florida State University, described D’OXYVA as a simple commercially available device used to deliver transdermal CO2 that has shown remote vasodilation, which may be mediated through the release of a circulating humoral agent.**

CO2 improves general healthcare in several ways:

· It has natural anti-inflammatory characteristics.

· It increases blood flow through microcirculation, by arteriolar/venous dilatation.

· It produces a rightward shift in the O2 dissociation curve.

· It enhances oxygen delivery at the cellular level in the muscles, organs, brain, skin and other parts of the body.

· It is a fat-dissolving compound.

· It naturally sedates and calms the central nervous system.

· It can be used to reconstruct functionally closed capillaries.

· It can improve venous response.

· It improves blood-flow properties.  It can be used to sedate the central nervous system.


Circularity Healthcare operates a state-of-the-art supply chain and quality management system (QMS) for manufacturing. Circularity has certificates of registration for IS EN ISO13485:2012 (European Union) and ISO13485:2003 under CMDCAS (Canada), which it has been implementing since 2013.

D’OXYVA is a CE-marked medical device (Class I, low risk) for delivery of medications via the skin. Circularity is seeking approval from the U.S. FDA and other countries for delivery of medical gases such as medical carbon dioxide (USP UN1013) via a novel, patented, non-invasive transdermal route with D’OXYVA to treat various widespread conditions.

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 through inhalation for humans but not yet through transdermal delivery with D’OXYVA. Transportation of medical carbon dioxide via any postal or courier service requires a certification for handling dangerous goods (HAZMAT) by the U.S. Department of Transportation (DOT).


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Blood Circulation Problems

Blood is the carrier of the all-important oxygen molecule. Through a series of reactions in which oxygen is involved, energy is produced, which is necessary for driving our cells’ metabolic reactions. So when blood does not reach a part of the body, the conditions that result from it are the consequences of oxygen deprivation. The heart, through its pumping action, maintains the pressure required for the blood to reach all parts of the body. Under normal circumstances, arteries, veins and capillaries, through which blood travels, are quite flexible. When they harden or get blocked, blood cannot flow through them to reach the organs. Hardening or blocking of blood vessels occur due to many reasons. Deposition of cholesterol and fat, clumping of platelets to form clots, and inflammation, all of these can lead to the narrowing of the diameter of blood vessels.

Problems in circulation also occur if the heart cannot pump blood efficiently. This can occur due to a number of reasons, but mostly is due to the same factors that are involved in blood vessel narrowing. Here are some conditions in which the blood circulation of an individual may get compromised.

It is the leading cause of narrowed blood vessels that ultimately lead to all kinds of problems in the body. Atherosclerosis is a gradual process of hardening and loss of flexibility of the arteries as a result of deposition of cholesterol and fats inside their lumen. These deposits are called plaques. When this deposition reaches a significant level, the arteries become partially or fully blocked. Blood cannot flow with the same efficiency through them, and the organ to which they supply suffers ischemia, a condition of oxygen deprivation. Atherosclerosis is the cause of many diseases like myocardial infarction, brain strokes, renal stenosis, and pain and cramps in the hands or legs. The disease which a person gets, depends on which arteries have significant blockage in them. Cholesterol is needed and manufactured naturally by the body, and it also comes into the body by the consumption of food, and excess amounts are stored. The same goes for fat – especially trans fat. A high fat diet is therefore one of the main culprits in causing atherosclerosis, although other factors like genetics are also important.

There is no easy way to get rid of atherosclerotic plaques, because they are quite tenacious. Lifestyle modification is an absolute necessity in preventing further damage to the arteries. In fact, nothing works as well as lifestyle modification in dealing with atherosclerosis. Other than this, the options available are for increasing the diameter of the narrowed arteries to restore normal blood flow.
  • Angioplasty – This procedure involves inserting a flexible tube in the artery and inflating it to increase its diameter.
  • Bypass Surgery – When the arteries supplying the heart (coronary arteries) are completely blocked, they are ‘bypassed” by using a blood vessel from some other part (e.g. leg). By surgically attaching this blood vessel to the heart, the blood supply is redirected via this, to the heart.
  • Preventive Measures – Changes in lifestyle, such as following a low-fat diet, exercising, reducing alcohol consumption, and cessation of smoking are necessary to avoid buildup of plaque in the arteries. Some drugs like statins can be used to lower cholesterol levels in the body, but they have many side-effects too.

This disease has two forms, a primary one, and a secondary form (called Raynaud’s phenomenon). The primary form does not occur in association with some other disease, but the secondary form does. In people suffering from this condition, some parts of the body such as the fingers, toes, nose, lips and ears feel very cold under conditions of low temperature or stress. This happens because some small arteries in these body parts constrict, reducing blood flow, causing the feeling of numbness and cold experienced by people suffering from this disorder. During an attack, the affected body parts blanch, and then turn blue. When blood flow is slowly restored, they turn red along with a burning, throbbing sensation. Many people with Raynaud’s disease experience all this only in their extremities. Its prevalence is greater among women as compared to men.

People with Raynaud’s disease are advised to wear warm clothes and not expose themselves to cold. They are also advised to stay away from drugs that cause blood vessel constriction. Most treatment options aim at dilating the constricted blood vessels which lead to the symptoms of Raynaud’s disease. If a patient has secondary Raynaud’s disease, the treatment for the underlying condition encompasses the treatment for Raynaud’s disease. If the patient does not get relief from these, or if the symptoms are very severe, surgical intervention or some other options may be resorted to.


  • Calcium Channel Blockers – These dilate blood vessels so that proper circulation to the extremities is restored. Some drugs in this category that are used are nifedipine, nicardipine and diltiazem.
  • Alpha-receptor Blockers – These drugs bind to alpha-1 receptors because of which norepinephrine is unable to bind to them. This prevents the constrictive effect of norepinephrine on the blood vessels. Some drugs in this class that are used are prazosin and doxazosin.

Other Options

  • Nerve Excision – Nerves that supply the blood vessels of the affected body part are cut so that they cannot cause them to constrict.
  • Amputation – Sometimes, gangrene develops in the part where the blood supply has been blocked. It needs to be surgically removed to prevent further spread.
  • Nerve Blockage – The nerves supplying the affected body part can be temporarily blocked to prevent blood vessel constriction.

Diabetes, as is well-known, is a complex metabolic disorder. The inability of the body to utilize glucose has system-wide effects, leading to all kinds of problems, from impaired wound-healing to neuropathies. One among the many problems stemming from diabetes is poor circulation. A high level of cholesterol and glucose in the blood, as well as high blood pressure, causes the blood vessels to thicken and lose their flexibility. This leads to insufficient blood supply to various organs, especially the hands and feet. The consequences of this reduced blood supply are many, like infections, delayed and impaired wound healing, numbness and coldness, tingling and difficulty in walking. If care is not taken, sores develop on the feet, which may advance to gangrene. Adding to the problem is the fact that diabetics often are overweight and have high blood pressure. All of these put them at an increased risk of heart problems as well. Diabetics often experience pain and cramping in the legs after a long walk or exercise. This is known as claudication.

Mostly, preventive measures undertaken to deal with atherosclerosis are recommended to patients with diabetes, for improving circulation. Without these, no amount of medication is enough to prevent circulation problems.

  • Quitting Smoking – Smoking has been strongly associated in a number of studies with the development of atherosclerosis. Quitting smoking is one of the most important steps that people with diabetes need to take to stop atherosclerosis.
  • Exercise – Physical activity, such as a daily walk, and exercise under supervision, greatly helps with improving circulation.
  • Other preventive measures include a healthy diet, not exposing the extremities to cold, and checking the feet for injuries, regularly.

Also known as Thromboangiitis obliterans, it is a disease of unknown cause, that has a strong association with smoking or chewing tobacco. This disease is characterized by inflammation of the veins and arteries of the extremities. They become inflamed and swell up, restricting blood flow to the hands and feet. Blood clots also form and further block the blood vessels. It is believed that some factors trigger the immune system to attack the blood vessels and cause inflammation. Insufficient blood supply to the limbs has the same effect on the hands and feet, as in other diseases, resulting from such a deficit – greater risk of infections, gangrene and tissue damage.

Most patients of Buerger’s disease are habitual tobacco users. Since tobacco use plays an important part in the genesis and progression of the disease, stopping smoking is the most important step in slowing the progression of the disease. Cessation of smoking improves the outcome of treatment, and slows the condition from aggravating further. Other than this, a treatment plan for Buerger’s disease involves therapies that increase blood flow to the limbs.

  • Streptokinase – This is an enzyme that is used to dissolve blood clots. It has been shown to be beneficial to a certain extent in patients of Buerger’s disease.
  • Synthetic Prostacyclin Analogues – Drugs belonging to this class, like iloprost, treprostinil and cicaprost, have been used with some success in dilating blood vessels in patients.
  • Surgery – Surgical options include sympathectomy (cutting off the nerve supply to the blood vessels), and in case of gangrene, amputation of the gangrenous part(s).
  • Some experimental therapies like the use of drugs to stimulate new blood vessels to grow are also being tried out.

There are a number of diseases that are caused due to formation of clots in the blood vessels, especially the veins. Valve defects, being on birth control pills for a long time, certain genetic conditions, injury, inflammation, certain congenital defects, some cancers, and many other factors predispose a person’s arteries or veins toward blood clot formation. These can be dangerous if not dealt with immediately.

It depends upon whether the clots are in the arteries or the veins.

  • Arterial Clots – Aspirin and clopidogrel, both prevent the blood platelets from sticking to each other. This helps in preventing clot formation. Heparin and some thrombolytic agents are also used to prevent clot formation.
  • Venous Clots – Heparin and warfarin, both are used to prevent clot formation in the veins.

Although some conditions in which there is a problem with blood flow are genetic in nature, most are preventable by bringing about lifestyle changes, such as following a healthy high-fiber diet, giving up smoking, and reducing consumption of alcohol.