Special article
Revisiting the essential role of oxygen in wound healing

https://doi.org/10.1016/S0002-9610(03)00211-3Get rights and content

Abstract

Hypoxemia, caused by disrupted vasculature, is a key factor that limits wound healing. Correcting hypoxemia through the administration of supplemental oxygen (O2) can have significant beneficial impact on wound healing in the perioperative and outpatient settings. Beyond its role as a nutrient and antibiotic, O2 may support vital processes such as angiogenesis, cell motility, and extracellular matrix formation. Recent discoveries highlight a novel aspect, addressing the role of O2 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 H2O2) from O2. Defect in these enzymes is associated with impaired healing. Low wound pO2 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 O2 therapy presents potential advantages, as well as risks. There is evidence to suspect that the use of pressure and systemic pure O2 may not be essential in wound care. Elimination of these factors by using sub-pure systemic O2 under normobaric conditions may significantly minimize the risk of O2 toxicity. Furthermore, opportunities to treat dermal wounds using topical O2 therapy warrant further investigation. Given that many growth factors require ROS for their function, it is reasonable to assume that approaches to correct wound pO2 will serve as an effective adjunct in treating chronic wounds.

Section snippets

Reactive derivatives of oxygen support healing: a new horizon

In the words of Thomas Hunt, a pioneer in the field of oxygen and wound healing, the search for the mechanisms by which O2 exerts its vital functions in wound healing has evolved another major step [3] making room for a new paradigm [4]. Recent discoveries have illuminated that not only phagocytes, but almost each and every cell in the wound microenvironment is fitted with a specialized enzyme to convert O2 to reactive oxygen species (ROS), including oxidizing species such as free radicals and H

Oxygen: beyond nutritional support

Angiogenesis is a critical early aspect of the wound healing response. While hypoxia can initiate neovascularization, it cannot sustain it. Supplemental O2 administration accelerates vessel growth [21]. It has been established that VEGF is a major long-term angiogenic stimulus at the wound site. O2 treatment induces VEGF mRNA levels in endothelial cells and macrophages [22], [23], [24] and increases VEGF protein expression in wounds in vivo [25]. Recently it has been shown that O2 may trigger

Oxygen as an antibiotic

Wound tissue pO2 levels are a major determinant of susceptibility to infection, and this has been shown both in experimental models and in human subjects. In a guinea pig model, the amount of skin loss seen after subcutaneous innoculation of bacteria was inversely proportional to wound oxygenation—hypoxic wounds were large, and the smallest wounds were seen in animals receiving supplemental O2. The efficacy of supplemental O2 in preventing skin loss was similar to antibiotic administration, and

Oxygen therapy: diagnostic, preventive and therapeutic

The availability of respired O2 to wound tissues depends upon vascular supply, vasomotor tone, arterial pO2, and the diffusion distance for molecular O2. Edema and necrotic debris both increase the diffusion distance for O2 to reach the wound, so debridement is an important step to diminish obstruction to wound oxygenation. Peripheral vasoconstriction can also significantly limit wound perfusion and oxygenation, so that little to no enhancement of wound pO2 levels are achieved despite breathing

Acknowledgements

Supported by GM27345 and DE013749 (seed) to CKS.

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