http://columbiamedicine.org/education/r/Cardiology/Outpatient-Prevention/PAD/LANCET%20review.pdf?origin=publication_detail

Peripheral arterial disease

The state of wound oxygenation is a key determinant of healing outcomes. From a diagnostic standpoint, measurements of wound oxygenation are commonly used to guide treatment planning such as amputation decision. In preventive applications, optimizing wound perfusion and providing supplemental O2 in the perioperative period reduces the incidence of postoperative infections. Correction of wound pO2 may, by itself, trigger some healing responses. Importantly, approaches to correct wound pO2 favorably influence outcomes of other therapies such as responsiveness to growth factors and acceptance of grafts. Chronic ischemic wounds are essentially hypoxic. Primarily based on the tumor literature, hypoxia is generally viewed as being angiogenic. This is true with the condition that hypoxia be acute and mild to modest in magnitude. Extreme near-anoxic hypoxia, as commonly noted in problem wounds, is not compatible with tissue repair. Adequate wound tissue oxygenation is required but may not be sufficient to favorably influence healing outcomes. Success in wound care may be improved by a personalized health care approach. The key lies in our ability to specifically identify the key limitations of a given wound and in developing a multifaceted strategy to specifically address those limitations. In considering approaches to oxygenate the wound tissue it is important to recognize that both too little as well as too much may impede the healing process. Oxygen dosing based on the specific need of a wound therefore seems prudent. Therapeutic approaches targeting the oxygen sensing and redox signaling pathways are promising.

/pdf/wound-healing-essentials-let-there-be-oxygen-4df1k4xtqz.pdf

Wound healing essentials: Let there be oxygen

Hypoxemia, caused by disrupted vasculature, is a key factor that limits wound healing. Correcting hypoxemia through the administration of supplemental oxygen (O(2)) can have significant beneficial impact on wound healing in the perioperative and outpatient settings. Beyond its role as a nutrient and antibiotic, O(2) may support vital processes such as angiogenesis, cell motility, and extracellular matrix formation. Recent discoveries highlight a novel aspect, addressing the role of O(2) in wound healing via the production of reactive oxygen species (ROS). Almost all wound-related cells possess specialized enzymes that generate ROS (including free radicals and H(2)O(2)) from O(2). Defect in these enzymes is associated with impaired healing. Low wound pO(2) is expected to compromise the function of these enzymes. At low concentrations, ROS serve as cellular messengers to support wound healing. The use of systemic hyperbaric O(2) therapy presents potential advantages, as well as risks. There is evidence to suspect that the use of pressure and systemic pure O(2) may not be essential in wound care. Elimination of these factors by using sub-pure systemic O(2) under normobaric conditions may significantly minimize the risk of O(2) toxicity. Furthermore, opportunities to treat dermal wounds using topical O(2) therapy warrant further investigation. Given that many growth factors require ROS for their function, it is reasonable to assume that approaches to correct wound pO(2) will serve as an effective adjunct in treating chronic wounds.

Revisiting the essential role of oxygen in wound healing.

A BSTRACT : Disrupted vasculature and high energy-demand by regenerating tissue results in wound hypoxia. Wound repair may be facilitated by oxygen therapy. Evidence supporting the mode of action of hyperbaric oxygen in promoting wound healing is sketchy, however. Topical oxygen therapy involves local administration of pure oxygen. The advantages of topical oxygen therapy include low cost, the lack of systemic oxygen toxicity, and possibility of home treatment. While this modality of wound care is of outstanding interest, it clearly lacks the support of mechanism-oriented studies. The search for mechanisms by which oxygen supports wound healing has now taken another step. Respiratory burst‐derived oxidants support healing. Oxidants serve as cellular messengers to promote healing. Although this information is of outstanding significance to the practice of oxygen therapy, it remains largely unexplored. The search for “natural remedies” has drawn attention to herbals. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Proanthocyanidins and other tannins facilitate wound healing. A combination of grape seed proanthocyanidin extract and resveratrol facilitates inducible VEGF expression, a key element supporting wound angiogenesis. Strategies to manipulate the redox environment in the wound are likely to be of outstanding significance in wound healing.

Oxygen, Oxidants, and Antioxidants in Wound Healing

Background— The Study to Assess the Safety of Intramuscular Injection of Hepatocyte Growth Factor Plasmid to Improve Limb Perfusion in Patients With Critical Limb Ischemia (HGF-STAT trial) determined the effect of hepatocyte growth factor (HGF) plasmid on safety and limb tissue perfusion as measured by transcutaneous oxygen tension (TcPo2) in patients with critical limb ischemia (CLI). Methods and Results— Randomized patients with rest pain or ischemic ulcers and TcPo2 <40 mm Hg and/or toe pressure <50 mm Hg received placebo or HGF-plasmid intramuscular injection as follows: 0.4 mg at days 0, 14, and 28 (low dose); 4.0 mg at days 0 and 28 (middle dose); or 4.0 mg at days 0, 14, and 28 (high dose). Patients were evaluated for safety, changes in TcPo2 and ankle and toe pressure, amputation, and wound healing. Ninety-three of 104 treated patients were evaluated for safety (mean age 70 years, 63% male, 53% diabetic, 64% with tissue loss, mean ankle-brachial index 0.41, and mean toe pressure 26 mm Hg). Adverse...

Results of a Double-Blind, Placebo-Controlled Study to Assess the Safety of Intramuscular Injection of Hepatocyte Growth Factor Plasmid to Improve Limb Perfusion in Patients With Critical Limb Ischemia

Transcutaneous Oxygen (TcPO2) Estimates Probability of Healing in the Ischemic Extremity

Role of leukocyte activation in patients with venous stasis ulcers

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Transcutaneous Oxygen (TcPO2) Estimates Probability of Healing in the Ischemic Extremity

Role of leukocyte activation in patients with venous stasis ulcers