Remote Ischemic Per-Conditioning

Abstract

Background and Purpose— Remote ischemic preconditioning is a phenomenon by which a short period of sublethal ischemia to an organ protects against subsequent ischemia in another organ. We have recently demonstrated that remote ischemic conditioning by transient hind limb ischemia delivered during ischemia and before reperfusion can provide potent cardioprotection, a phenomenon we termed per-conditioning. This study evaluated whether remote ischemic per-conditioning may provide neuroprotection in a clinically relevant rat model of acute ischemic stroke. Methods— Remote ischemic conditioning by transient limb ischemia was used in a rat transient middle cerebral artery occlusion model of acute stroke. A total of 39 P60 rats were randomly allocated to receive preconditioning, per-conditioning, or sham conditioning. Cerebral ischemia was maintained for 120 minutes followed by reperfusion. The resulting infarct size at 24 hours was quantified using computerized image analysis of 2–3-5-triphenyl tetrazolium chloride-stained brain sections. Results— Compared with control, both pre- and per-conditioning significantly reduced brain infarct size with the more clinically relevant per-conditioning stimulus being superior to preconditioning. Conclusions— Remote per-conditioning by transient limb ischemia is a facile, clinically relevant stimulus that provides potent neuroprotection in a model of regional brain ischemia–reperfusion injury. Further studies are required to better understand the mechanisms and biology of this response before translation to randomized controlled trials of remote per-conditioning for acute ischemic stroke.