LIMITING OXYGEN DELIVERY ATTENUATES INTESTINAL REPERFUSION INJURY

Since free radical-mediated injury is dependent on the reintroduction of oxygen into ischemic tissues, restriction of oxygen content in the initial reperfusate has therapeutic potential. The degree to which oxygen must be restricted is crucial since hypoxic injury would continue if reperfusion O2 delivery remained below the ischemic threshold of the tissue. We examined this treatment strategy in 20 pump-perfused intestinal preparations subjected to 30 min of flow interruption. The oxygen content of the reperfusate was varied by utilizing arterial (A) or venous (V) blood; as a further modification, we also performed experiments in which hemodiluted arterial blood (HD) was the reperfusate at normal (NHD) and high (HHD) flow rates. The flow rates and O2 contents of the reperfusates were adjusted to produce either high (∼ 12 ml O2/min/100 g) or low (∼ 8 ml O2/min/100 g) levels of O2 delivery. Histologic sections, obtained after ischemia and after 1 hr of reperfusion, were blindly evaluated for mucosal injury (1 = normal to 5 = severe injury). Immediately after 30 min of ischemia, all groups had comparable histologic grades (A 2.0 ± 0.3, V 1.8 ± 0.3, NHD 1.6 ± 0.3, HHD 2.3 ± 0.3). One hour after reperfusion, intestines reperfused with blood with high O2 content and hence high O2 delivery showed significantly more damage (P < 0.001) than those with exposed to low O2 delivery during reperfusion: A 3.9 ± 0.5 and HHD 4.4 ± 0.4 versus V 2.7 ± 0.5 and NHD 2.9 ± 0.3. While it is accepted that reintroduction of O2 during reperfusion is the crucial step in the genesis of reperfusion injury, it is remarkable that such modest reductions in total O2 delivery (approximately 30%) are effective in decreasing mucosal injury. In our model of intestinal ischemia, this degree of O2 restriction does not result in significant depression of intestinal O2 consumption or continued hypoxic injury and therefore has therapeutic potential. © 1992.