Limiting oxygen delivery attenuates intestinal reperfusion injury

Abstract

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 (approximately 12 ml O2/min/100 g) or low (approximately 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.(ABSTRACT TRUNCATED AT 250 WORDS)