Hypoxia and Oxygen Free Radical Damage

Hypoxia and Oxygen Free Radical Damage

Hyperbaric oxygen therapy does not cause free radical damage but this is a frequently raised objection. Fridovich

(1) was the first to publish that it is LACK of oxygen that creates the conditions for free radical damage. He discussed three possible scenarios.

1. The formation of free radicals increases when the level of oxygen in the tissue actually reduces.

2. The accumulation of substances when there is an insufficient level of oxygen causes free radical formation when normal levels of oxygen are restored.

3. White cells are programmed and congregate in the brain during hypoxia and activate the 'respiratory burst' normally responsible for microbial killing.

All three are probably valid and are interlinked, but the white cell effects can be seen. Fridovitch predicted the effects link free radical injury to inflammation. In infection white cells stick to the lining of blood vessels at the infection site (2) by detecting changes due to lack of oxygen. In both inflammation and reperfusion injury white cells stick to the lining of blood vessels and then pass through into the tissues to generate a burst of oxygen free radicals to kill the invaders. (3) This defense mechanism is wrongly activated when blood flow is restored in an organ after a period of arrest. Zamboni et al (4) stopped the blood flow in muscle for four hours and on restoring flow found white cells sticking to the wall of veins and then passing through, leading to the death of the muscle tissue. A high level of oxygen stopped the cells sticking and death of the muscle tissue was prevented.

The relevance to the practice of Medicine? The use of high dosage oxygen to treat ANY condition where blood flow is significantly reduced or stopped, especially organ transplantation and to protect the brain when the circulation is restored after cardiac arrest.

1. Fridovich I. Hypoxia and oxygen toxicity. Adv Neurol 1979;26:255-59.

2. Clark ER, Clark EL. Amer J Anat 1936;59;123

3. Babior BM Oxygen dependent microbial killing of phagocytes N Engl J Med 1978;298:721-725.

4. Zamboni WA et al.Morphologic analysis of the microcirculation during reperfusion of ischemic skeletal muscle and the effect of hyperbaric oxygen.

Plast Reconstr Surg 1993;91:1110-1123

Best wishes to all

Philip James

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