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

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

ABOUT THE AUTHOR

Judy Delp Ph.D.

Job Description

Professor of Biomedical Sciences

 

Education

B.S. Rockhurst University, Kansas City, Missouri

Ph.D. University of Missouri

 

Memberships

American Physiological Society

American Microcirculatory Society

American Heart Association

Toriyama et al.17 studied the effect of CO2 bathing in 83 limbs with critical ischemia and achieved limb salvage in 83% without surgery. They concluded that peripheral vasodilation from CO2 bathing resulted from an increased parasympathetic and decreased sympathetic activity. In the current study, treatment with transdermal CO2 in a localized area produced a sustained, remote vasodilation, and a lowering of systemic blood pressure.
 
These findings share some similarity with the hemodynamic changes that occur following an acute bout of exercise, in which both neural and vascular components contribute to a sustained decrease in vascular resistance and blood pressure that persists after cessation of exercise18. In the current study, the period of sustained vasodilation seen in response to transdermal CO2 was heightened in diabetic patients.
 
Interestingly, in hypertensive individuals, the period of post-exercise hypotension is of greater magnitude and duration as compared to that of normotensive individuals 18, 19. Paradoxically, the current findings in diabetic patients exposed to transdermal CO2 as well as previous findings in hypertensive patients post-exercise, imply that sensitivity to signals that mediate these cardiovascular responses increases in patients with pre-existing cardiovascular dysfunction19.
 
A sustained decrease in systolic blood pressure occurs post-exercise and here, following application of transdermal CO2, suggesting that neural mechanisms contribute to the observed reduction in systemic vascular resistance. The roles of efferent sympathetic nerve activity18-20, afferent nerve activity from muscle 21-24, and the baroreceptor reflex20, 23 in mediating post-exercise hypotension remain controversial.
 
Neural mechanism(s) could contribute to changes in skin SPP and systolic blood pressure induced by exposure to transdermal CO2. Future studies will need to monitor heart rate, heart rate variability, and sympathetic nerve activity during and after transdermal CO2 in order to more fully assess the role of the autonomic nervous system in mediating the sustained increases in SPP and systolic blood pressure reported in this initial study.
 
Vascular conductance increases in both active muscle and inactive vascular beds following a bout of dynamic exercise 25, 26, suggesting that circulating factors contribute to this period of sustained systemic vasodilation. Vasodilation occuring independently of neural regulation constitutes more than 50% of the increase in systemic vascular conductance that occurs post-exercise; however, the mechanisms that underlie the post-exercise vasodilation have remained elusive.
 
Studies that have employed blockade of nitric oxide or evaluation of circulating nitric oxide metabolites have shown that the post-exercise vasodilatory response does not rely on circulating nitric oxide availability27, 28. A recent study by New and colleagues28 indicates that the nadir of post-exercise hypotension coincides with the peak of appearance of lipid hydroperoxides in venous blood, suggesting that reactive oxygen species with known vasodilatory properties29-32 contribute to the exercise-induced decrease in systemic vascular resistance. In the current study, transdermal CO2 was applied to the thumb, and a significant increase in SPP was measured at the toe.
 
Thus, a similar circulating vasodilatory stimulus may contribute to the remote, sustained vasodilation created by local transdermal application of CO2. Further investigations will need to focus on the identification of the mechanisms involved in both the local and remote factors that contribute to the sustained hemodynamic changes produced by exposure of the skin to CO2.
 
Recently, studies have documented that episodes of brief, non-damaging ischemia occurring in a tissue can induce systemic protection against ischemia-reperfusion injury in a remote organ. This phenomenon, termed remote ischemic conditioning, has been demonstrated to confer protection against ischemic events in the myocardium33-35, brain36, and kidney37, 38.
 
Although shown to be effective in various clinical and pre-clinical models 34, 35, 38-40, the mechanism(s) of remote protection have not been clearly identified. Both neural and humoral mechanisms have been proposed to contribute to the protection against ischemic damage afforded by remote ischemic conditioning38, 39, 41-43.
 
Basalay et al.41 have shown that when remote ischemic conditioning is applied before induction of myocardial ischemia, sensory nerves and recruitment of a parasympathetic neural pathway are involved in reduction of infarct size. In contrast, application of remote ischemic conditioning after myocardial ischemia also afforded protection against infarction, but was not altered by vagotomy or peripheral denervation41.
 
Remote ischemic conditioning has also been demonstrated to improve perfusion of transplanted kidneys, suggesting that remote conditioning confers protection that does not rely on intact neural circuitry38. Recently, Michelsen and colleagues42 have demonstrated that dialysate of human plasma from subjects who underwent either ischemic preconditioning or exercise preconditioning reduced infarct size in rabbit hearts, indicating that release of a humoral factor, possibly acting on opioid receptors, contributes to the cardioprotective effects of ischemic and exercise preconditioning.
 
Other reports in the literature have also shown evidence of a humoral substances that mediate protection against ischemia when remote ischemic conditioning is applied; however, these substance(s) remain to be identified. Application of transdermal CO2 produces a remote vasodilation that may be mediated through release of a circulating humoral agent.
 
Future investigations will need to focus on assessment of plasma samples during and following transdermal CO2 application.
This pilot study demonstrated an increase in measures of remote skin microvascular function with D’OXYVA, a simple commercially-available device to deliver transdermal CO2. The effects of the treatment were evident at all periods up to and including the last test period, 240 minutes post-exposure.
 
Although the sample size was small in this study, a clear increase in SPP and SPP/SBP ratio and a decrease in SBP and DBP continued for 4 hours post-treatment. The differences in skin perfusion and blood pressure responses detected between diabetic and non-diabetic subjects will require further examination in larger studies.
 
Click below to access Prof. Judy Delp’s Presentation on Transdermal Delivery of Carbon Dioxide Boosts Microcirculation.
 

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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“People are dying”: Diabetics rationing insulin amid rising drug prices

Drug manufacturers were grilled Wednesday about the skyrocketing price of insulin, which has doubled in the last five years and led some patients to ration the life-saving drug. One study finds the underuse of insulin could affect nearly 40 million people with diabetes by 2030.

“Nobody cared or nobody understood that without this next vial of insulin, I wouldn’t live to see another week,” said 28-year-old Kristen Whitney Daniels.

She started rationing her insulin after she was kicked off her parents’ insurance plan two years ago.

“I can’t really explain how isolating and how terrifying it is,” she said.

She’s now a patient at the Yale Diabetes Center, where a recent Journal of American Medical Association study found one in four patients reported “cost-related underuse.” Dr. Kasia Lipska treats patients at the clinic, and was the study’s lead author. She testified on Capitol Hill last week.

  • Woman says her son couldn’t afford his insulin – now he’s dead
  • Eli Lilly rolling out half-price insulin. Diabetics say it’s not enough

“This vial of insulin cost just $21 when it first came on the market in 1996. It now costs $275,” she said.

Some drug makers are already reacting to the outrage. On Wednesday, Sanofi announced it will cut the price of insulin for uninsured patients and those who pay cash to $99 per month. But that doesn’t eliminate advocate concerns.

“People are dying from lack of access to a drug that has been around for almost a century. I think it’s unconscionable,” Lipska said.

Insulin manufacturers told CBS News they’ve taken steps to address prices, including offering free medication to people who quality.

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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Circularity Healthcare Presenting D’OXYVA Diabetic Wound Healing Microcirculation Therapy Clinical Evidence and Sponsoring the 3rd International Microcirculation Conference – ESM-EVBO 2019

It is with our great pleasure to announce that we were invited by the organizers to participate in the 3rd joint ESM-EVBO 2019 and become a sponsor.

The 2019 ESM-EVBO (European Society for Microcirculation – European Vascular Biology Organization) Conference will be held on April 15-18 and hosted at the MECC in Maastricht, The Netherlands.

The conference focuses on advancing scientific research and medicine in all areas of vascular biology/medicine. Biennially, the ESM-EVBO hosts a four-day conference, where vascular enthusiasts from biology, preclinical and clinical research groups, and opinion leaders gather to share new fundamental scientific insights and current pre-clinical advances. Its network now has over 500 members worldwide, including representation in over 30 countries.

Besides being accepted into the poster sessions, Circularity is sponsoring the international symposium on Microcirculation.

Prof. Ito Puruhito, a distinguished thoracic vascular surgeon at Airlangga University, in Surabaya, Indonesia has been conducting several successful human clinical studies with D’OXYVA at the university over the past few years, and he is presenting some of his latest clinical evidence on diabetic foot ulcer treatment with D’OXYVA on April 17, 2019: http://esm-evbo2019.org/program/lunch-symposium/.

Want to stay updated on this event and what will happen next? Register your email for free now and follow the news about groundbreaking health discoveries!

About ESM (European Society for Microcirculation)

The European Society for Microcirculation was founded in Hamburg in 1960 following a first meeting of interested scientists in Lund, Sweden in 1959, and now has 500-600 regular members. The aims of the Society are to advance understanding of the microcirculation by bringing together clinicians and scientists from a wide range of specialists, but including physiology, vascular biology, genetics and biophysics.

Since 1980, the Society has its own journal, the Journal of Vascular Research, an international publication of growing impact, through which the world wide scientific community is informed of the Society’s endeavors.

About EVBO (European Vascular Biology Organization)

EVBO was launched in 2006, after discussion between European vascular biologists who recognized that there is a need for a democratic society to provide a united focus and forum for vascular biologists in Europe, primarily by organizing conferences but also by maintaining and enhancing an interactive network of researchers; evolving from the experience of the previous European Vascular Biology Association and building on the achievements of the FP6 European Vascular Genomics Network (EVGN).

 

About Circularity Healthcare

Circularity Healthcare, LLC, headquartered in Los Angeles, California in the U.S., is an emerging world leader in proprietary circulatory health and noninvasive delivery technologies, committed to helping significantly improve lives by developing, manufacturing, and marketing medical, pharmaceutical, and consumer health products. Circularity specializes in groundbreaking noninvasive technologies for affordable and portable transdermal delivery systems, and is pursuing regulatory approvals worldwide for device usage as a treatment of disease states related to cardiovascular and microcirculatory blood flow, immunological and autonomic nervous system disorders.

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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Have you heard of Tere’s inspiring diabetic story?

“My Doctor told me I have less than a year to live if I won’t let them amputate my leg, but I didn’t let them . . . here’s how I am still alive now!”

When doctors initially told 60-year-old Theresa “Tere” Schaufer that she had diabetes, she went into denial for 20 years.

“I was diagnosed with diabetes 20 years ago, and only when my doctor told me that they needed to cut my leg, did I realize that my diabetes was serious,” she says.

 

A major contributing factor

“Doctors told me the only way to survive this fight was to amputate my leg,” Schaufer says.  

She acknowledges that she had lived an unhealthy lifestyle for many years. Working in a restaurant as a cashier, she did very little exercise, ate fast food and drank sodas on a regular basis.

“If the doctor tells you you’re a diabetic, don’t ignore it. Don’t get to where I am. The sooner you accept things, the better it is for your health.”

Only after her doctor advised amputation did she realize the seriousness of her situation. Schaufer’s lifestyle had a hugely negative impact on controlling her diabetes. 

 

It was very painful!

Schaufer had puss from underneath her foot and necrotic toe. “After the doctor examined my foot, it was like decaying,” she says. “I couldn’t handle the pain. It was excruciating!” She was given less than a year to live because of her poor lifestyle.

 

I started to accept the situation.

Schaufer finally accepted her fate as a diabetic after the doctor told her that her leg would have to be amputated.

“I saw it coming. The pain was terrible. I could no longer handle it. At this point I was prepared; whatever came had to be.”

 

Unexpected turn of events

“I was browsing a support page I found on the web and read about a colleague’s experience with the microcirculation therapy she had tried. She noted that it had an amazing effect on her diabetic foot ulcer,” Schaufer says.

Right there on the support page, the woman raved, “There is this new technology you can buy online, D’OXYVA, which was voted one of the Top 10 Diabetes Care Solution Providers 2018! I didn’t have to amputate my leg because of this amazing product. In just four weeks, I can see my diabetic foot ulcer improving!”

“I read these words, and it gave me the hope I’d been praying for,” noted Schaufer.

She only had a month before her scheduled amputation, and without hesitation, she used the remaining days to try out D’OXYVA. She ordered the product online and closely collaborated with their in-house support.

“I was under D’OXYVA therapy for one month, taking it twice a day, once in the morning and once before bed as advised. It was very easy to use and non-invasive. In the first few days, I was skeptical as I wasn’t seeing any improvements, but I continued anyway and followed their suggested therapy guide,” Schaufer explains.

 

Thankful for D’OXYVA

When it was time for her to go back to her doctor and give her consent to amputate, her doctor was shocked to see her leg.

“What happened?” Those were the exact words my doctor asked upon seeing my leg after only a month. “Your wounds seemed to be healing from the inside,” my doctor said.

After a thorough check-up and the usual diagnostic check of my foot’s PI (perfusion index), he said the words that I never expected to hear. “We don’t need to amputate your leg anymore, but you need to continue whatever you’ve been doing for the past month.”

I then introduced him to D’OXYVA, and he was amazed by how this product had saved me.

 

Helping others

“I’m on my third month of D’OXYVA therapy, and it does amazing things for my health! I don’t think I have thanked D’OXYVA enough for this chance to live longer. I wouldn’t have the outlook on life that I have now,” Schaufer continues cheerfully.    

She is now also leading a healthy life. “This changed how I live my life, and I will continue sharing my experience as much as I can to help others.”

Schaufer often spends time with other “to-be-amputees” struggling to deal with their situation. “God gave me my situation to help others,” she maintains.

One of the ladies she counselled remarked how Schaufer had helped her tremendously. “She told me that I gave her her life back,” Schaufer says, breaking into tears.

“I’m in a way thankful for what I have been through with my diabetes because, without it, I wouldn’t have stumbled across my strength and my ability to help others.”

HOW CAN D’OXYVA 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

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.

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

doxyva benefits

OPTIMIZE BLOOD CIRCULATION FOR A WIDE VARIETY OF SIGNIFICANT OUTCOMES

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

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

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

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

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

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

HOW D’OXYVA CAN HELP?

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

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

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Anesthesia, Microcirculation, and Wound Repair in Aging

Abstract

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.

 

Summary

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.

 

 

Reference: http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1917910

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Blood, Oxygen & Wound Healing: How It Works

Most of us take our natural wound-healing abilities for granted. You scrape your knee, clean it and wait for it to heal on its own. It seems pretty simple, right? Not exactly. The truth is, what goes on underneath that Band-Aid is a complex process that requires healthy blood flow to deliver the oxygen and nutrients necessary to heal, and if this process is interrupted, it can slow or prevent healing entirely.

 

Wound-Healing Process

Every wound goes through a continuous repair and healing process, which typically takes a few weeks to complete. For a wound to heal properly, the four wound-healing stages must be completed:

Stage 1: Hemostasis

Hemostasis happens immediately after an injury to skin causes bleeding. Your blood vessels constrict and reduce the flow of the blood to the injury site. Blood clots form within the injured blood vessels to prevent further blood loss.

Stage 2: Inflammation

Once a blood clot has closed the wound, the surrounding blood vessels are able to open up to deliver fresh nutrients and oxygen into the wound for healing. This process triggers macrophage, a white blood cell, to enter the wound, fight infection, oversee the repair process and send messengers, called growth factors, needed to heal the wound. Macrophage is the clear fluid you may see in or around the wound.

Stage 3: Proliferation

Proliferation is the growth and rebuilding phase, where blood cells arrive to help build new tissue to replace the tissue and cellular elements that were damaged during the process of wounding the skin. At this point, your body’s cells will produce a protein called collagen, which acts like scaffolding, to support the repair process.

Stage 4: Remodeling

The last wound-healing stage is remodeling, whereby the inflammation is gradually resolved and the collagen is deposited. New tissue takes the form of the original tissue and fills the area of the wound. We call this scar tissue, and while the wound may appear to have healed, it does not have the same strength as the normal tissue previously had. It may take several months to a year for the healed wound to gain full strength.

 

When Wound Healing Is Interrupted

For healthy adults, the four wound-healing stages progress naturally. For others, however, certain factors – especially poor circulation – can interrupt the body’s natural healing process, causing a wound to heal much more slowly, if at all. These wounds are called chronic wounds (wounds that do not heal in six to eight weeks despite normal treatment) and are most common in people with diabetes, high blood pressure, obesity and other vascular diseases. If not cared for or treated by a doctor, chronic wounds can lead to pain, infection, disability and possibly amputation of the affected limb.

 

Tips for Improving Circulation

The oxygen and nutrients that new blood carries to the wound are crucial to the healing process. By improving circulation and blood flow, more healing nutrients and oxygen reach the cells.

 

Eat a healthy diet.

A healthy diet promotes proper blood flow and can even speed up the wound-healing process. Eat the following power foods to make sure you are getting the right nutrients for optimal circulation and wound healing:

Protein: Lean meats, low-sodium beans, low-fat milk and yogurt, tofu, soy nuts and soy products

Vitamin C: Citrus fruits and juices, strawberries, tomatoes, spinach, potatoes, peppers and cruciferous vegetables

Vitamin A: Dark green, leafy vegetables; orange or yellow vegetables; cantaloupe and fortified cereals or dairy products

Zinc: Red meats, seafood and fortified cereals

 

Quit smoking.

There are a number of reasons to quit smoking and better your health. Beyond increasing risk for cancer and heart disease, tobacco can cause poor circulation and delayed wound healing. If you smoke, consult your doctor to devise a smoking cessation plan.

 

Stay hydrated.

Dehydration and poor hydration can greatly reduce circulation of blood and body fluids. Dehydration can also lead to poor oxygen perfusion, a failure to deliver essential nutrients to the wound surface and draining inefficiency. Drink eight 8-ounce glasses of water each day to improve blood flow and wound-healing abilities.

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Being mindful of symptoms

LEWISTOWN–Dr. Maya Lichtenstein, neurologist at Geisinger-Lewistown Hospital, said that there are a myriad of potential symptoms that could be signs of a stroke. “Any sudden changes,” said Lichtenstein, “go the E.R.”

A stroke, according to Liechtenstein, is either the result of not enough blood flow to the brain, plaque in the blood vessels or heart, each resulting in a clot, or a hemorragic bleed, resulting in a bursted blood vessel in the brain. Classic symptoms of a stroke include numbness, tingling, weakness on one side of the body and changes in speech, but other sudden changes in in understanding language, vision, vertigo or clumsiness can also be symptomatic.

“It depends on what part of the brain is damaged,” said Lichtenstein.

Treatment options for a stroke vary, depending on the type of stroke.

“If you get seen fast enough,” said Lichtenstein, for a clot, a “clot-busting medication, a form of blood thinner” can be administered via I.V. A thrombectomy, a procedure, not an operation, said Lichtenstein, is another treatment option, similar to a cardiac catheterization. A bleeding stroke often leads to lowering the patient’s blood pressure and surgically relieving pressure on the brain. Taking aspirin can also treat a stroke.

Post-stroke, Liechtenstein said that rehabilitation is important, including physical, occupational, speech, and cognitive therapies. “Aggressive therapy can continue to improve people’s symptoms,” said Lichtenstein. “Everyone thinks they’re better if they can move their arms and legs.” Lichtenstein also encourages stroke patients to be aware of their mood and possible depression, encouraging them to accept all the help available.

To avoid a stroke, Liechtenstein said patients should see their doctors regularly for preventive care and that leading a healthy lifestyle is the key, including regular exercise to keep up the heart rate and eating a diet rich in fresh fruit and vegetables, lean proteins and whole grains. Lichtenstein also encourages patients to keep control of their vascular issues, such as high blood pressure and diabetes, as well as to quit smoking, if they smoke.

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Do You Know the Importance of Early Detection of Microcirculatory Impairment in Diabetic Patients?

diabetes

OBJECTIVE:

To assess microcirculatory impairment and alterations of the skin oxygen supply in diabetic patients with foot at risk.

RESEARCH DESIGN AND METHODS:

This study evaluated skin blood flow in 21 type 2 diabetic patients with a foot at risk (defined as a foot with neuropathy but without ulceration or previous ulcerations), 20 type 2 diabetic patients without foot lesions or neuropathy, and 21 normal subjects as a control group. The skin blood flow was determined by measuring the transcutaneous oxygen pressure (TcPO(2)) at the dorsum of the foot in supine and sitting position. The clinical assessment included standard measures of peripheral and autonomic neuropathy, but peripheral vascular disease was excluded by Doppler ultrasound.

RESULTS:

In supine position, TcPO(2) was significantly reduced (means +/- SE) in diabetic patients with foot at risk (6.04 +/- 0.52 kPa) compared with diabetic (7.14 +/- 0.43 kPa, P = 0.035) and nondiabetic (8.10 +/- 0.44 kPa, P = 0.01) control subjects. The sitting/supine TcPO(2) difference was higher in diabetic subjects with foot at risk (3.13 +/- 0.27 kPa) compared with both diabetic (2.00 +/- 0.18, P = 0.004) and nondiabetic (1.77 +/- 0.15 kPa, P = 0.0003) control subjects. The mean sitting/supine ratio was 1.70 +/- 0.12 in diabetic patients with foot at risk, 1.32 +/- 0.04 in diabetic control subjects, and 1.25 +/- 0.03 in nondiabetic control subjects (P = 0.007). The sitting/supine TcPO(2) ratio was negatively correlated with the heart rate variation coefficient at rest (r = -0.32, P = 0.044) and at deep respiration (r = -0.31, P = 0.046).

CONCLUSIONS:

Our data indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot at risk. This is probably due to an impaired neurogenic blood flow regulation and may contribute to capillary hypertension, followed by disturbed endothelial function leading to edema and skin damage of the foot. The determination of TcPO(2) appears to be a useful tool in screening type 2 diabetic patients for foot at risk.

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.