Controlled low-flow reperfusion after warm brain ischemia reduces reperfusion injury in canine model

Acute occlusion of the carotid artery caused by acute type A aortic dissection (AAD) induces on-going warm brain ischemia. The purpose of this study was to elucidate the hypothesis that low-flow reperfusion could mitigate reperfusion injury after warm ischemic damage to the brain.

Experiments were performed using a canine global brain ischemia model, with 15 minutes of ischemia followed by 3 hours reperfusion, which was established by a simple brain reperfusion circuit with a roller pump. The right common carotid artery (RCCA) flow ratio was determined as the mean RCCA flow during reperfusion divided by the mean RCCA flow during pre-ischemia. Animals were divided into two groups according to the RCCA flow ratio; low RCCA flow ratio of 0.3 to 0.6 (Group L, n=5) and control RCCA flow ratio of 1.0 to 1.4 (Group C, n=5). At the 3-hour reperfusion time point, physiological and histopathological assessments were performed in both groups.

Electroencephalographic activity recovered in four of five animals (80%) animals in Group L, whereas no recovery (0%) in activity was observed in Group C. Brain water content in Group L animals was significantly less than that in Group C. Apoptosis, number of perivascular edematous regions and NFkappaB expression were apparently suppressed in Group L compared with Group C. There were significant positive correlations of RCCA flow with brain water content, apoptosis and number of perivascular edematous regions.

Controlled low-flow reperfusion mitigated reperfusion-induced brain edema and apoptosis, leading to rescue of brain function in the canine model.