Intermittent ischemia potentiates intestinal reperfusion injury

Abstract

We hypothesized that even brief periods of reperfusion interjected between ischemic episodes would increase tissue injury. Studies were performed in a rat small intestine preparation in which metabolic, hemodynamic, and histologic responses to ischemia have been well characterized. Animals were subjected to a total of 30 or 45 minutes of complete intestinal ischemia. Flow interruption was continuous (C, single episode) or intermittent (I, two or three episodes of 15-minute ischemia separated by 5 minutes of reperfusion). In some experiments 5-minute reperfusions were performed with arterial blood depleted of leukocytes (IL). This additional perturbation was included to determine the role of neutrophils that have been strongly implicated in reperfusion injury. In all three protocols histologic sections were obtained after each ischemic insult and after 1 hour of reperfusion with arterial blood. Villous histology was graded in a blinded fashion with 1 = normal and 5 = severe injury. No significant differences were found between groups in immediate postischemic histologies before reperfusion. After 1 hour of reperfusion, intermittent episodes of ischemia were associated with significantly worse histologic injury than that seen with comparable durations of continuous ischemia (30 min: I, 4.4 ± 0.5 vs C, 2.7 ± 0.4; 45 min: I, 4.9 ± 0.2 vs C, 2.8 ± 0.3). However, if 5-minute reperfusions were with leukopenic blood, this effect was markedly reduced (30 min IL, 3.4 ± 0.3; 45 min IL, 3.6 ± 0.2). Even short periods of reperfusion during an ischemic insult greatly increased mucosal injury. This likely resulted from increased access of leukocytes to ischemic tissues during the brief reperfusion periods, since decreasing leukocyte availability by transiently reperfusing with leukopenic blood attenuated the damage. Maneuvers designed to limit leukocyte adherence to endothelial cells should be considered in the treatment of intestinal ischemia, particularly in patients at risk for repeated episodes of flow interruption.