Protective effects of ischemic postconditioning compared with gradual reperfusion or preconditioning.

We examined the temporal factors of postconditioning, assessed whether gradual reperfusion reduces infarcts, and compared postconditioning's protection with that of both rapid and delayed preconditioning. Focal ischemia was generated by permanent occlusion of the left distal middle cerebral artery (dMCA) combined with 30 min of occlusion of both common carotid arteries (CCA) in rats. Postconditioning was performed by repetitive brief release and occlusion of CCA after 30 min of CCA occlusion. Gradual reperfusion was generated by controlled release of the bilateral CCA. We confirmed that postconditioning disrupted the early reperfusion but improved cerebral blood flow (CBF) thereafter. Postconditioning with three cycles, but not with 10 cycles, of 30 sec CCA release and 10 sec CCA occlusion (30s/10s) reduced infarction measured at 2 days after stroke. In addition, postconditioning with 10 cycles, but not with three cycles, of 10s/10s reduced infarction but it lost protection when initiated at 3 min after reperfusion. In addition, gradual reperfusion also reduced infarction. Moreover, both rapid and delayed preconditioning conducted 60 min and 3 days before stroke reduced infarct sizes. However, no additional protection was detected when postconditioning was combined with either rapid or delayed preconditioning. In conclusion, gradual reperfusion reduced infarction; postconditioning's protection depended on the number of cycles and duration of each cycle of reperfusion and occlusion and the onset time of postconditioning; postconditioning's protection was comparable to that of rapid preconditioning but not as robust as that of delayed preconditioning.