Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo

Background-Endothelial dysfunction leading to neutrophil infiltration of ti ssues has been implicated in tissue injury caused by ischemia-reperfusion ( IR). Tissue injury during IR can be reduced by prior ischemic preconditioni ng (IPC). In humans, it is unclear whether endothelial dysfunction occurs d uring IR or whether IPC offers protection against endothelial dysfunction a nd inflammatory cell activation. We studied the effects of experimental IR on endothelial and neutrophil function in the human forearm in vivo and exa mined the protection afforded by IPC. Method and Results-The forearm was made ischemic for 20 minutes by inflatin g a blood pressure cuff to 200 mm Hg. We assessed endothelial function of c onduit (radial artery flow-mediated dilation) and resistance vessels (blood flow responses to intra-arterial infusion of the endothelium-dependent dil ator acetylcholine) in healthy volunteers before and after IR, IR reduced f low-mediated dilation of the radial artery at 15 minutes of reperfusion (7. 7 +/-1.5% to 3.5 +/-0.9%) and the dilator response of resistance vessels to acetylcholine at 15, 30, and 60 minutes of reperfusion, IR did not reduce the dilator response of the radial artery to glyceryltrinitrate and only ca used a small reduction of glyceryltrinitrate-induced dilation of resistance vessels at 60 minutes of reperfusion, IR caused an increase in neutrophil CD11b expression and platelet-neutrophil complexes in the circulating blood . IPC (three 5-minute episodes of ischemia) before IR prevented endothelial dysfunction and neutrophil activation. Conclusions-A clinically relevant period of ischemia-reperfusion causes pro found and sustained endothelial dysfunction and systemic neutrophil activat ion. IPC attenuates both of these effects in humans.