Chronic or non-healing wounds tend to exhibit low oxygen tensions. If the amount of wound tissue that is poorly oxygenated falls below a critical mass, the wound becomes "dormant" and the body no longer recognizes the need for healing. The tissue pO2 level below which it is generally believed that wound healing is impaired is 30 mmHg or less. The oxidative phosphorylation process in the mitochondria requires a minimum oxygen tension of 0.5 to 3 mm Hg in the mitochondria. The critical mass or percentage of wound tissue that must fall below these levels before a wound becomes "non-healing" is not known at this time.

In the past it was believed that the only way to increase tissue oxygen levels was through super oxygenation of the blood by breathing oxygen under high pressure, 2-3 atmospheres. The inherent problem with this approach is that it relies on the existing microvascular structure to carry the oxygenated blood to the site of the wound. If the wound tissue itself is poorly vascularized, the diffusion distance oxygen must travel to reach the ischemic cells reduces the effectiveness of this systemic approach.

When 100% oxygen is applied directly to an open, moist non-healing wound, at a pressure slightly above one atmosphere, oxygen is dissolved in the wound fluid and then absorbed by ischemic surface wound tissue. It has not yet been demonstrated how deep or how many cell layers the oxygen will penetrate. However, the cells that do absorb oxygen will commence metabolic activity in response to the increased oxygen tension.

When the external oxygen source is removed, the cellular oxygen tension drops rapidly because there is insufficient vascularity in the wound tissue to maintain the increased oxygen levels. As this state of "relative hypoxia" occurs, the cells respond by sending out biochemical signals that more oxygen is needed. The body's response is to produce cytokines that lead to the formation of new blood vessels since this is the only mechanism for providing the additional oxygen needed. This is the start of the healing process.

Topical oxygen therapy protocols call for repeating this "high" oxygen state followed by relative hypoxia on a regular schedule. The protocol consists of one and one-half hours per day of oxygen therapy for four consecutive days, followed by three days without the oxygen therapy. The same cycle is repeated as many weeks as necessary to reach the "critical mass" of oxygenated tissue. The three days of rest is necessary to prevent possible cell damage caused by an excess of oxygen which can lead to the formation of active oxygen species such as free radicals which are cytotoxic. Although the current protocol has been proven effective, the "ideal" protocol, i.e. one which optimizes healing while minimizing tissue damage needs to be verified through controlled studies. The optimum pressure, length of time of oxygen exposure and time between treatments for different types of wounds would be determined in such studies.