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Microcirculation: Exploring and understanding the unknown

cancer

Everything is in the microcirculation. According to Dr. Ricardo Quintos II, most medical problems, particularly serious ones like stroke, kidney failure or heart attack, can trace its roots to circulation.

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Medical practitioners need to focus on, and have a better understanding of, the blood flow through the smallest vessels in the circulatory system, or microcirculation, he said. Just like vascular surgery, of which Dr Quintos is a pioneer of in the Philippines, he is now setting his sights on looking at the unseen.

“One of the reasons that made me go into vascular is the realization that all these organs are served by the vascular tree,” Quintos told MIMS in an interview.

The vascular tree is made up of arteries, arterioles, capillaries, venules and veins. All together, these constitute the complex system that is at the heart of circulation – capillary exchange.

To illustrate the importance of microcirculation, Quintos used cancer as an example.

One reason there is cancer is because of a disordered growth in the vascular tree supplying cancer cells with too much blood and nutrients, he explained.

Using chemotherapy agents is not the answer to treat the cancer because not only will it kill the cancerous cells, but also the normal ones. The better treatment course is to address the vascular problem. – Dr. Ricardo Quintos

“What you do is just starve the cancer cells. You give antiandrogenic substances so that vascular tree will just shrink. And once that happens, they will have no more blood and will just die.”

A second example is how to treat vascular problems when a patient has a heart attack. Instead of doing a bypass to allow more blood to go to the heart, Quintos recommended making the heart “grow its own arteries.” More specifically, to give androgenic factors to make the arteries grow its own bypasses, which is not only less risky but also more natural.

“And that is what we mean by looking into the microcirculation,” Quintos stressed.

The vascular surgeon said they have put up their own microcirculatory laboratory and undertaken research on microcirculation.

“All of these vascular procedures will not work if your microcirculation is not working,” he explained.

He said a heart attack is not the result of blockage in the arteries of the heart, but rather the microcirculation of the heart is not working very well, because the cells there are poor. The brain, Quintos pointed out, stops working not due to poor circulation but because microcirculation to the brain breaks down.

Having made great inroads in the field of vascular surgery, Quintos now sees microcirculation as the future in medical treatment.

“We have to look into what we cannot see before. And the thing we cannot see in the vascular world is microcirculation,” he said, adding, “Ultimately, it’s all for the patient.”

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Why Use D'OXYVA?

The link between oxygen and cancer is clear. In fact, an underlying cause of cancer is usually low cellular oxygenation levels.

In 1931 Dr. Warburg won his first Nobel Prize for proving cancer is caused by a lack of oxygen respiration in cells. He stated in an article titled “The Prime Cause and Prevention of Cancer… the cause of cancer is no longer a mystery, we know it occurs whenever any cell is denied 60% of its oxygen requirements…”

D’OXYVA® (deoxyhemoglobin vasodilator) is an over-the-counter (OTC) device, which is the first biotech solution of its kind backed by widely-established groundbreaking Nobel Prize-winning science validated to significantly improve macro-, and micro-circulation of blood flow and certain nerve activities in the body such as the autonomic nervous system, which together are widely reported to form an effective solution option for many of the most severe and widespread health conditions.

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Yusuf Myers; a regular on the Dr. Oz Show on working out from home

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In the middle of a global pandemic, prioritizing your health and wellness is one of the smartest moves you can make. That’s true for everyone, but for Black Americans, it’s critical as this group faces a disproportionate rate of COVID-19 hospitalizations and death, according to the Centers for Disease Control and Prevention. 

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Yusuf Myers, the founder, creator, and owner of PRX Workouts, emphasized the importance of self-care, like fitness, at a critical time like this. After all, some research suggests exercise may help reduce the risk of a severe respiratory complication called acute respiratory distress syndrome.

“I do not believe the problem is a lack of understanding of the importance of exercise, [because] Black people are very physical in their everyday lives and work,” he said. “However, there is a lack of viable, affordable resources and options for the Black community.” 

Staying fit at home

Fortunately, you don’t need professional workout equipment to give your immune system a lift. Myers recommends starting small with simple exercises like burpees, jumping jacks, high knees, and standing up and sitting down on the couch or a chair. 

“All these movements you can do from anywhere,” he said. “You do not need to be in a gym to practice them.”  

He added that the goal is to get your heart rate up. “Other great examples include HITT training, walking outside with a mask on, taking the stairs, changing your rituals, and adding movement to your rituals.”

If you’re looking for a specific routine to get started, Myers recommended the following:

“Try doing 30 seconds of jumping jacks, then 30 seconds of an active rest, and then 30 seconds of jumping jacks again,” Myers said. “As you start to build your cardiovascular endurance and increase blood flow, you can continue to increase the time to 45 seconds, then to a minute.”

Nutrition-wise, he suggested cutting back on saturated fats and watching your caloric intake.

Finding support

Finally, he recommended building — and then leaning on — your support system, whoever that may be. 

“I have created a platform and community filled with unity, trust, integrity, and a positive outlet to learn and grow for oneself and for others,” Myers said. “Not only during a trying time like COVID-19, but always.”

To stay motivated, Myers said you should seek out a virtual workout buddy or join an online program you think you’d enjoy. If you’re new to working out, trust the process. 

“My job as a fitness leader in my community and virtually, touching people around the country and the world on social media, is to get people to realize nothing is impossible with hard work and consistency,” Myers said.

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Why Use D'OXYVA?

Experts say D’OXYVA can help COVID-19 patients find relief. Preliminary medical data shows people with pre-existing conditions including diabetes may experience serious complications from COVID-19.

D’OXYVA helps by delivering transdermal ultra-purified medical gas directly to the blood stream delivering major outcomes for well over 90% of users.

Experts call D’OXYVA a gamechanger.

“Studies with D’OXYVA have shown unmatched results in noninvasive woundcare,” Dr. Michael McGlamry.

Anyone with an underlying condition should know this option is available.

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New CDC data shows danger of coronavirus for those with diabetes, heart or lung disease, other chronic conditions

D'OXYVA | Cardiovascular, Diabetes Care, Pain Reliever in CA.

People who have chronic medical conditions, such as diabetes, lung disease and heart disease, face an increased chance of being hospitalized with covid-19 and put into intensive care, according to data released Tuesday by the Centers for Disease Control and Prevention that is consistent with reports from China and Italy.

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The new data gives the most sweeping look at the way covid-19 is causing serious illnesses among people in the United States who already face medical challenges.

The report reinforces a critically important lesson: Although the disease is typically more severe among older people, people of any age with underlying medical conditions are at increased risk if they contract the virus, for which there is no vaccine or approved drug treatment. 

The CDC data is an initial description of how the disease appears to be affecting people who are already dealing with health challenges. The study did not break down the disease demographically, for example by age, sex, race or income. The agency also notes that this is essentially a snapshot and can’t capture the ultimate outcome for people who have been infected with the virus and haven’t yet recovered.

The report shows covid-19 is thrusting vulnerable people in the United States into intensive care units and disproportionately taking the lives of people who already face medical challenges.

The CDC analyzed more than 7,000 confirmed covid-19 cases across the country in which health officials had a written record about the presence or absence of any underlying medical condition. The preexisting conditions covered in the records include heart and lung diseases, diabetes, chronic renal disease, chronic liver disease, immunocompromised conditions, neurological disorders, neurodevelopmental or intellectual disability, pregnancy, current or former smoker status, and “other chronic disease.”

The CDC found that, of people requiring admission to an intensive care unit, 78 percent had at least one underlying health condition. Of people hospitalized but not requiring ICU admission, 71 percent had at least one such condition, compared with just 27 percent of people who didn’t need to be hospitalized.

Among all the cases analyzed, 10.9 percent of patients had diabetes mellitus, 9.2 had chronic lung disease and 9 percent had cardiovascular disease.

The report did not reach any conclusion about whether the severity of an underlying condition correlated to a more severe covid-19 illness.

Of the 7,160 patients whose chronic illness status was known through health records, 184 died, and 173 of them had an underlying condition, the CDC said. None of the deaths were among people under age 19.

Covid-19 is a respiratory disease. The virus typically infects the upper respiratory tract, but it can also venture deeper into the lungs and in some patients results in pneumonia-like symptoms, requiring hospitalization and sometimes intubation on a ventilator. People who smoke or have chronic lung conditions are especially vulnerable.

Diabetes and heart disease are similarly worrisome. Someone already suffering from heart problems — whether they had previous heart attack or required a stent installed because of plaque buildup in their vascular system — may have a heart that cannot take as much strain as the average person, said Amesh Adalja, an infectious disease physician at Johns Hopkins Center for Health Security.

When a patient gets infected with something like this coronavirus, the fever causes a spike in the heart rate. Shortness of breath means the patient gets less oxygen. People with limited cardiac capacity can go into arrest.

Diabetes is a metabolic syndrome that involves blood glucose levels and affects how the immune system works, and makes it less effective, Adalja said.

“This is why patients with diabetes are at risk for many infections not just coronavirus,” Adalja said. “They often struggle with infections on their skin and soft tissues, with pneumonia and even more serious conditions.”

Those in the high risk group need to be extremely careful.

“If they do become infected, the threshold for them seeking medical attention needs to be much lower. They and their clinicians have to keep this in mind,” Adalja said. “These numbers show us just how crucial that is.”

Wilbur Chen, an infectious-disease physician at the University of Maryland, added that while the virus seems to prey on the elderly and sick, “it does not mean it does not cause severe illness in younger adults or in children — in other words, the risk is not zero among the young.”

He said, “We are now documenting a large number of covid-19 infections across the U.S. and we are now observing more and more of these ‘rare’ events of severe illness and even deaths among the young.”

HOW D’OXYVA CAN HELP?

D’OXYVA works to prevent sepsis, and resulting septic shock, using life-restoring molecule carbon dioxide (CO₂) and gentle vapor dissolved across the skin in a fast, painless, handheld  5-minute application — performed either in a clinical setting or in the comfort and privacy of your own home.

D’OXYVA is the only fully noninvasive, completely painless over-the-skin microcirculatory and nerve stimulant solution that has been validated 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.

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‘It literally came out of nowhere’: Mom, 39, warns others after suffering heart attack

D'OXYVA | Cardiovascular, Diabetes Care, Pain Reliever in CA.

Jennifer Andrews was driving on a New Jersey highway last month when she suddenly suffered a massive heart attack. As she fell unconscious behind the wheel, her car careened down an embankment and stopped in heavy brush and trees. A Good Samaritan who saw what happened and followed had to resuscitate her three times to get her heart beating normally again.

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At 39, Andrews had never experienced any heart issues or symptoms before and was “completely blindsided,” she said.

“It literally came out of nowhere,” Andrews, an executive assistant who lives in borough of Washington, New Jersey, told TODAY. “It’s extremely scary. I feel like this is something that happens to 80-year-old men.”

Andrews was even more stunned since she had just gone to her primary care doctor for her annual checkup just two weeks before the episode. All the bloodwork came back fine, as did checks of her heart rate and blood pressure, she noted. She exercised regularly and led a low-stress life.

The mother of two did have risk factors, including smoking a few cigarettes a day, being overweight and having a family history of heart disease — her father died of heart problems in his mid-50s — but said it never crossed her mind to worry about her heart at her age.

After waking up in the hospital four days after the January 9 accident, Andrews was incredulous when doctors told her she had a 100% blockage in one of her coronary arteries, requiring a stent.

“I didn’t believe them. If it wasn’t for me waking up in the hospital with the tubes in my arm and the oxygen in my nose — and I could tell I had been intubated because my throat was hurting — I would have never believed it,” she said.

Know the risk factors and symptoms

It’s possible for people to do everything right and still have heart problems sneak up on them, said Dr. Sharonne Hayes, a cardiologist and founder of the Women’s Heart Clinic at the Mayo Clinic in Rochester, Minnesota. 

February is American Heart Month, an annual campaign to raise awareness of heart disease — the leading cause of death for both men and women in the U.S., yet many people still think of it as a “man’s illness.”

The risk goes up as people age, so heart attacks in premenopausal women are not common, but they do happen, Hayes noted. A recent study found heart attacks are on the rise in women between the ages of 35 and 54.

It leads expert to wonder: Are doctors are not paying enough attention to those women’s risk factors, or is the type of heart disease younger women develop fundamentally different than heart disease in the elderly or in men? The answer is probably a combination of both those factors, Hayes said.

Her research interest is spontaneous coronary artery dissection — a tear in a coronary artery wall — which often affects women who are otherwise healthy, with few or no risk factors for heart disease, according to the American Heart Association.

Hayes advised women under 50 who have suffered a heart attack with no risk factors to talk to their doctor about whether they had a SCAD or another heart attack cause not related to plaque buildup.

Hayes didn’t treat Andrews, but said it’s understandable why she would feel blindsided. A typical 39-year-old woman may be more focused on reproductive issues or the risk of breast cancer than her heart health because she probably doesn’t have any friends and family her age who have heart disease, Hayes noted.

The key for everyone is to pay attention to risk factors — including high blood pressure, unhealthy cholesterol levels, diabetes, excess weight, smoking and a family history of heart disease — and address the ones you can control.

For example, even light smoking — like the three or four cigarettes a day Andrews smoked before her accident — is a compelling risk factor for heart disease, Hayes said.

“But even people who optimally control all the risk factors still could have a heart attack,” Hayes said.

“Recognize it could happen and know what to do if you get the symptoms or somebody around you gets the symptoms.”

Chest pain is still the No. 1 warning sign for both sexes, but women can also experience different symptoms than men, including pain in the neck, jaw, throat, abdomen or in the upper back between the shoulder blades.

Andrews did have some upper back pain in the weeks leading up to her heart attack, but said that was typical for her and the condition was being treated by a chiropractor.

Since the heart attack, Andrews has quit smoking, is watching her salt, fat and cholesterol intake and feels fine, she said. There are new medications to take and doctors to visit during her follow-up care. The accident left her with bruising from the seat belt, but she’s recovering well.

“It was very eye-opening,” Andrews said about the ordeal, noting she was indebted to everyone who saved her life.

“I feel like ‘thank you’ isn’t enough. I don’t know what to say for them to understand how grateful I am.”

HOW D’OXYVA CAN HELP?

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

Taking D’OXYVA® daily promotes benefits related to significantly improved blood circulation, including significantly increased cardiac activity, physical fitness, metabolism, endurance, energy balance and a healthy weight.

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Treating Microcirculation Defects in Cardiovascular Diseases

D'OXYVA | Cardiovascular, Diabetes Care, Pain Reliever in CA.

Defects in microcirculation have been documented as major factors in the development of cardiovascular diseases, especially type 1 diabetes.[1] By treating microcirculation defects, thus increasing blood and oxygen flow to the heart, the risk of recurrent significant cardiovascular events can be reduced significantly, and strength and endurance can improve. 

An example of microcirculation compromise in a patient with severe cardiovascular disease can be seen in the clinical case of Leo B.

Leo was a 64-year-old male with a medical history of diabetes mellitus for 15 years, cigarette smoking, elevated cholesterol, and high LDL (harmful blood fat) levels. 

Leo had a heart attack (myocardial infarction) several years ago.

He had suffered a myocardial infarction 6 weeks earlier and also suffered from exertional angina (chest pain with exertion).

He was taking lisinopril (20 mg per day) for high blood pressure, insulin for his diabetes, and one baby aspirin a day as a blood thinner to prevent another heart attack.

Leo was put on a cardiac rehabilitation regimen[2] consisting of a low-fat diet, moderate exercise, and stress control. 

He used D’OXYVA[3]as an adjunct application, which helped increase his strength and endurance while decreasing his episodes of exertional chest pain.

What is Microcirculation? 

In general, microcirculation[4] refers to the smallest blood vessels in the body, consisting of the arterioles, venules, and capillaries. 

These tiny blood vessels supply oxygen to the organs of the body and remove waste products produced by the body’s metabolism. 

Smooth muscle cells, which are the lining cells of the arterioles and of some venules, are under the control of the sympathetic and parasympathetic nervous systems and other chemical factors. 

These influences help control the ability of the microcirculatory system to dilate and contract to increase or decrease circulation and oxygenation.

What is Coronary Microcirculation? 

Coronary microcirculation (microvascular network) refers to the smallest arterioles and venules that supply the heart. 

These tiny branching blood vessels play crucial roles in supplying oxygen and removing waste products from the heart muscle. 

When the heart requires more oxygen, the arterioles dilate, increasing blood flow to the heart. 

This is especially important if a patient suffers from cardiovascular conditions such as angina or heart failure. 

What Causes Cardiac Microcirculation Dysfunction? 

Dysfunction of cardiac microcirculation can be caused by many factors, including:

  • Dysfunction of the endothelial (lining) cells of the arterioles, which affects the ability of arterioles to dilate and allow for increased blood flow
  • Increased alpha 2 adrenergic activity, which leads to vasoconstriction and resultant decreased cardiac perfusion
  • Sclerosing of the arterioles, causing reduced blood flow and oxygenation 
Conclusion 

Microcirculation consists of the smallest blood vessels in the body and includes cardiac microcirculation, which plays a crucial role in supplying oxygen and removing waste products from the heart. The transdermal deoxyhemoglobin vasodilator D’OXYVA plays an important role in increasing blood flow (perfusion) and resultant oxygenation to the cardiovascular system. This increase in oxygenation has been found to help increase endurance and strength and is an important adjunct solution to consider as part of cardiac rehabilitation.

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless over-the-skin microcirculatory solution that has been validated 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.

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Diabetes, cardiovascular disease and the microcirculation

D'OXYVA | Cardiovascular, Diabetes Care, Pain Reliever in CA.

Abstract

Cardiovascular disease (CVD) is the leading cause of mortality in people with type 2 diabetes mellitus (T2DM), yet a significant proportion of the disease burden cannot be accounted for by conventional cardiovascular risk factors. Hypertension occurs in majority of people with T2DM, which is substantially more frequent than would be anticipated based on general population samples. The impact of hypertension is considerably higher in people with diabetes than it is in the general population, suggesting either an increased sensitivity to its effect or a confounding underlying aetiopathogenic mechanism of hypertension associated with CVD within diabetes. In this contribution, we aim to review the changes observed in the vascular tree in people with T2DM compared to the general population, the effects of established anti-diabetes drugs on microvascular outcomes, and explore the hypotheses to account for common causalities of the increased prevalence of CVD and hypertension in people with T2DM.

Background

Type 2 diabetes mellitus (T2DM) and hypertension are established risk factors for cardiovascular disease (CVD), and people with T2DM and hypertension have an increased risk of cardiovascular (CV) mortality compared with those with either condition alone. This excess risk is suggested to be due to the synergistic effect on large and small blood vessels simultaneously, thereby reducing the potential for compensatory collateralization protecting organs from the adverse consequences of damage to either vascular bed. The principle role of the vasculature is to deliver oxygen and nutrients to the tissues—whether that is the heart, the brain, or the kidney. The functional changes occurring in T2DM and hypertensive conditions significantly alter the hemodynamic stress on the heart and other organs. However, the different physiology, mechanisms and changes at the microvascular level differ from those at the macrovascular level in T2DM and hypertension, which in turn have significant implications with respect to future CV risk.

Conclusions

Over the past few decades, epidemiological studies have elucidated the role of impaired microcirculation in people with diabetes and aetiopathogenesis of CVD. This has led to the recognition of the prevalence of microvascular disease. Furthermore, the prognostic value of incidence of microvascular disease in predicting CVD is now acknowledged. The focus of present-day epidemiological studies is to understand the association between pathological mechanisms and the risk factors to ascertain whether they are targets of therapeutic value or risk markers of CVD. These studies have contributed to the evidentiary framework in favor of clinical monitoring of microvascular function, and spurred the initiation of mechanistic studies by redefining our knowledge of vascular disease, particularly in people with diabetes.

HOW D’OXYVA CAN HELP?

Over the past few decades, epidemiological studies have elucidated the role of impaired microcirculation in people with diabetes and aetiopathogenesis of CVD. 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.

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Under Armour developing ‘smart’ sneaker that reads blood pressure

D'OXYVA | Cardiovascular, Diabetes Care, Pain Reliever in CA.

Under ArmourOpens a New Window. is developing a “smart” sneaker that would track the blood pressure of its wearer, according to a patent filing this week.

The sports apparel brand’s filing with the U.S. Patent and Trademark Office details two versions of a sneaker currently in development. The first version of the sneaker would link to a wearable device and transmit blood pressure that would then be used to adjust the sneaker’s fit for optimal blood flow. The second version of the sneaker contains a “blood pressure detector.”

In the patent filing, Under Armour said the sneaker is meant to help its wearer recover after a “strenuous workout.”

“There exists a need for a device and method to effectively pump blood through the plantar venous plexus and support recovery after engaging in athletic activity,” the company wrote in its filing, dated June 25.

Under Armour representatives did not immediately respond to a request for comment. Baltimore Business Journal was first to report on the filing.

The filing comes as Under Armour and other sports apparel companies seek to integrate technology into their products.

The Baltimore-based company unveiled its first smart shoe, the “HOVR Connected Series,” in 2018. The footwear line measures a runner’s gait and other workout data.

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. 

D’OXYVA promotes benefits related to significantly improved blood circulation, including significantly increased cardiac activity, physical fitness, metabolism, endurance, energy balance and a healthy weight by significantly improving Microcirculation that is detectable real-time with high quality diagnostics.

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.

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The Alzheimer’s-blood pressure connection

D'OXYVA | Cardiovascular, Diabetes Care, Pain Reliever in CA.

Rock legends David Bowie and Freddie Mercury must have known something that science discovered only recently. In their rock anthem “Under Pressure,” they crooned: “Pressure pushing down on me … Chipping around, kick my brains around the floor.”

Researchers wouldn’t put it quite that way, but there is a correlation between a person’s elevated blood pressure later in life and brain health, particularly Alzheimer’s disease risk. A study in Neurology recorded the blood pressure of 1,300 people ages 59 to 102 annually for a mean of eight years. Brain autopsies of deceased subjects then revealed a link between high blood pressure and the presence of neurofibrillary tangles, characteristic of Alzheimer’s disease.

An elevated systolic, or top number, above 134 mmHG increased the odds of developing brain lesions by nearly 50%. But according to Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Weill Cornell Medicine and New York-Presbyterian, anything above 120 puts you in the “new risk zone.” The study didn’t find a correlation with an elevation of the diastolic (the bottom number) and Alzheimer’s.

The good news: Lifestyle changes can help you achieve a healthy blood pressure of around 120/75. The DASH, Mediterranean and “What to Eat When” diets are a smart starting point. Check out Sharecare.com for info on these nutritional approaches and to download a free phone app to keep track of your numbers. Plus, ask your doc about medications and at-home, self-measured blood pressure monitors; the cuff ones are usually reliable, but should be checked against one at your doc’s office.

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.

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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?

D'OXYVA | Cardiovascular, Diabetes Care, Pain Reliever in CA.

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

D'OXYVA | Cardiovascular, Diabetes Care, Pain Reliever in CA.

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 occurring 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.
 

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.

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Impaired Tissue Perfusion

D'OXYVA | Cardiovascular, Diabetes Care, Pain Reliever in CA.

What is Impaired Tissue Perfusion?

Ineffective tissue perfusion is a state in which an individual has a decrease in oxygen resulting in failure to nourish the tissues at the capillary level.

Tissue perfusion is a critical parameter for tissue survival and function, and both relative and absolute perfusion assessments are highly relevant for both diagnosis and evaluation of the therapy response.

Sometimes situations occur where this exchange of gases between the blood and the cells is disrupted, meaning the cells (and ultimately the tissues and organs) stop getting adequate oxygen supply. The body can’t function without oxygen, so obviously this is a problem. When tissues don’t receive enough oxygen through the capillaries, this is called ineffective tissue perfusion.

Many conditions can disrupt the exchange of oxygen and carbon dioxide, but diabetes, obesity, anemia, high blood pressure, and coronary artery disease are some of the more common risk factors that can cause ineffective tissue perfusion. We can further classify the type of ineffective tissue perfusion based on the part of the body affected. For example, there’s renal (meaning kidney), cerebral (meaning brain), cardiopulmonary (meaning heart and lungs), gastrointestinal (meaning digestive tract), and peripheral (meaning affecting the extremities) ineffective tissue perfusion.

Common Risk Factors

Small arteries in diabetic subjects, whether hypertensive or normotensive, exhibit severe hypertrophic remodeling, and histological analysis of skeletal muscle biopsy samples reveals capillary rarefaction in subjects with type 2 diabetes. Histological capillary density is inversely related to fasting plasma glucose and fasting insulin levels and positively related to insulin sensitivity in nondiabetic individuals. Microvascular permeability to large molecules such as albumin is increased in diabetes, a process that is linked to hyperglycemia and ROS

In humans, coronary flow reserve is significantly lower in obese than in nonobese subjects, and capillary recruitment is reduced in nondiabetic obese individuals compared with lean control subjects. Even in a sample of healthy children (11 to 14 years of age), microvascular function was negatively correlated with adiposity. Thus, obesity appears to have an independent effect on microvascular function.

Coronary flow reserve decreases progressively with age in subjects without coronary artery disease, from approximately 4 at 30 years to 3 at 65 years of age, largely due to increased basal myocardial blood flow.

Tobacco smoking acutely impairs capillary recruitment, and thus hyperemic blood flow increases in skin and coronary flow reserve is reduced in established smokers. Coronary flow reserve in smokers can be improved by administration of antioxidant vitamin C, which suggests that smoking-related oxidative stress is an important mechanism.

Individuals with hypercholesterolemia without coronary artery disease have reduced coronary flow reserve, and coronary flow reserve is inversely correlated with LDL cholesterol. A reduction in coronary flow reserve can be detected in healthy young men (mean age 31 years) with familial hypercholesterolemia, which suggests that microvascular abnormality is detectable early in the atherosclerotic process.

Given the relationships between individual cardiovascular risk factors with measures of microvascular status, it is not surprising that the overall Framingham risk score is inversely correlated with skin capillary recruitment, maximal skin capillary density, and coronary flow reserve.

Defining Characteristics

Ineffective Tissue Perfusion is characterized by the following signs and symptoms:

  • Abnormal arterial blood gases
  • Altered respiratory rate outside of acceptable parameters
  • Bronchospasms
  • Capillary refill >3 seconds
  • Chest pain
  • Chest retraction
  • Dyspnea
  • Dysrhythmias
  • Nasal flaring
  • Sense of “impending doom”
  • Use of accessory muscles
  • Altered mental status
  • Behavioral changes
  • Changes in motor response
  • Changes in pupillary reactions
  • Difficult in swallowing
  • Extremity weakness or paralysis
  • Speech abnormalities
  • Abdominal distention
  • Abdominal pain or tenderness
  • Hypoactive or absent bowel sounds
  • Nausea
  • Altered sensations
  • Altered skin characteristics (hair, nails, moisture)
  • Cold extremities
  • Dependent, blue, or purple skin color
  • Diminished arterial pulsations
  • Edema
  • Positive Homan’s sign
  • Skin discolorations
  • Skin temperature changes
  • Skin color pale on elevation, color does not return on lowering the leg
  • Slow healing of lesions
  • Weak or absent pulses
  • Altered blood pressure outside of acceptable parameters
  • Elevation in BUN/creatinine ratio
  • Hematuria
  • Oliguria or anuria

Damage, Complications, and Prognosis

Microvascular abnormalities that lead to impaired tissue perfusion appear to represent a generalized condition that affects multiple tissues and organs. For example, in hypertension, coronary flow reserve is correlated with the media:lumen ratios of small arteries in biopsies of subcutaneous fat. Dilatation of venules in the retina independently predicts progression of cerebral small-vessel disease, and in diabetes, reduced coronary flow reserve predicts the occurrence of retinopathy.

Impaired tissue perfusion may be involved in target-organ damage and complications that involve several vascular beds. For the coronary microcirculation, an obvious example associated with both hypertension and diabetes is the occurrence of myocardial ischemia and angina in the presence of angioscopically normal epicardial coronary arteries, also known as cardiac syndrome X. Impaired myocardial perfusion may also be an important factor in the development of hypertensive heart failure and may lead to localized ischemia and disturbed patterns of electrical activity that constitute a substrate for serious arrhythmias. In the case of renal disease, glomerular and peritubular capillary rarefaction has been noted in different animal models and in human progressive renal disease, and it precedes the development of impaired perfusion and chronic hypoxia. It has been suggested that hypoxia may be the common factor linking many forms of progressive renal disease.

Microvascular abnormality is also a predictor of prognosis. In hypertensive patients, the media:lumen ratio of peripheral small arteries is a strong independent predictor of cardiovascular events. Among individuals with normal or minimally diseased coronary arteries, reduced coronary flow reserve is an independent predictor of cardiovascular events within the next decade. Finally, in patients with chest pain and angiographically normal arteries, coronary flow reserve <3 is associated with a 6-fold increase in all-cause mortality risk compared with coronary flow reserve >3 during 8.5 years of follow-up.