Ischemia-reperfusion syndromes are well defined clinical entities although the mechanism explaining the entire process still needs to be elucidated. The re-oxygenation phase is characterized by an arterial vasoconstriction, activation of platelets and leukocytes, a release of inflammation related mediators and increased free radical production. The therapeutic approaches aim to reduce the negative effects related to re-oxygenation. Both experimental models and clinical studies demonstrate a favorable effect by the administration of hyperbaric oxygen, even when it seems paradoxical. Given the variety of models used to study the individual components involved in ischemia-reperfusion, it is difficult to determine which factor is affected predominantly by hyperbaric oxygen and which generates the observed beneficial outcome. In the mean time, several questions remain unanswered. Significant differences on the effect of hyperbaric oxygen are observed between in vivo and in vitro models. Extrapolation from animal models to human clinical practice is inappropriate because of the interspecies94 and inter-strain differences in expression and distribution of enzymes and adhesion molecule, and immunologic reactions.

The favorable effect of hyperbaric oxygen is determined by the duration and the degree of ischemic hypoxia, the duration of secondary ischemia and the time and dose of administration of hyperbaric oxygen.

Defining research protocols remains difficult because of the lack of effective classification of the degrees or grades of ischemia. An interesting point, however, is the differential effect of hyperbaric oxygenation on normoxic tissues compared to hypoxic tissues.

In the future, clinical evidence should assist in identifying the window of opportunity for HBO administration during ischemia-reperfusion. It seems quite obvious as far as the inflammatory cascade is concerned, probably neither HBO nor any other drug alone will be sufficient to completely reverse all aspects of the inflammatory cascade during ischemia-reperfusion.

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