Oxygen: an anti-inflammatory drug.

• Vol 9 • December 2007 874 Impaired tissue oxygenation and cellular hypoxia are major components in the pathophysiology of a large variety of clinical conditions, including acute and chronic ischemia, wounds and tissue trauma, infections, physical and chemical injuries, as well as inflammatory joint and connective tissue diseases [1]. Tissue hypoxia triggers an inflammatory response. Mechanisms of the intimate relationship between hypoxia and inflammation are gradually being elucidated and are expected to lead to the development of new treatment modalities to alleviate local destruction and also harness the systemic effects of exaggerated inflammatory response [1]. Evidently, the purpose of hypoxia-induced inflammation is to combat invasive microorganisms, clear tissue debris, and enhance tissue repair. However, too often the delicate balance between beneficial and potentially detrimental consequences of inflammation is impaired, causing local tissue damage and frequently culminating in a systemic inflammatory response that involves many organs and may lead to multiple organ dysfunction and failure [2]. In light of the key role of tissue hypoxia in the initiation and propagation of local and systemic inflammatory responses, evaluating the effects of treatment with oxygen at high ambient partial pressures in these conditions is called for. Inhalation of oxygen increases oxygen delivery. A small addition to oxygen delivery is attained by an increase in hemoglobin saturation to 100%, and a significantly higher increment is achieved by physically dissolved oxygen in the plasma. The amount of dissolved oxygen increases in direct proportion to the ambient pressure. Altogether, this accounts for a rather modest (~10%) increase in arterial blood oxygen content during inhalation of 100% oxygen at normal atmospheric pressure, and a 30% increase during hyperbaric exposure to oxygen at 3 atmospheres [3,4]. The amount of physically dissolved oxygen in the plasma during exposure to 100% oxygen at 3 atmospheres (about 6 vol%) is sufficient to meet the average requirements of the tissues by means of dissolved oxygen alone. It should be emphasized, however, that the predominant change in oxygen availability to tissues during exposure to hyperoxia is not solely dependent upon the increase in oxygen content but is determined by the much more significant increase in arterial blood oxygen partial pressure. This increases from around 90 mmHg while breathing air at normal atmospheric pressure to values five to sevenfold higher while breathing 100% oxygen at normal atmospheric pressure, and may reach values higher than 2000 mmHg during hyperbaric exposure at 3 atmospheres. This rather dramatic increase in arterial blood oxygen pressures and the manifold increase in oxygen partial pressure gradient from the blood to the tissues account for the markedly facilitated diffusion of oxygen to tissues during hyperoxic exposures and to significantly improved tissue oxygenation [3,4].