Ischaemia-reperfusion injury impairs tissue plasminogen activator release in man

Christian M Pedersen, Gareth Barnes, Michael R Schmidt, Hans Erik Bøtker, Rajesh K Kharbanda, David E Newby, Nicholas L Cruden

Research output: Contribution to journalArticlepeer-review


AimsIschaemia-reperfusion (IR) injury causes endothelium-dependent vasomotor dysfunction that can be prevented by ischaemic preconditioning. The effects of IR injury and preconditioning on endothelium-dependent tissue plasminogen activator (t-PA) release, an important mediator of endogenous fibrinolysis, remain unknown.Methods and resultsIschaemia-reperfusion injury (limb occlusion at 200 mmHg for 20 min) was induced in 22 healthy subjects. In 12 subjects, IR injury was preceded by local or remote ischaemic preconditioning (three 5 min episodes of ipsilateral or contralateral limb occlusion, respectively) or sham in a randomized, cross-over trial. Forearm blood flow (FBF) and endothelial t-PA release were assessed using venous occlusion plethysmography and venous blood sampling during intra-arterial infusion of acetylcholine (5-20 µg/min) or substance P (2-8 pmol/min). Acetylcholine and substance P caused dose-dependent increases in FBF (P
Original languageEnglish
Pages (from-to)1920-7
JournalEuropean Heart Journal
Issue number15
Publication statusPublished - Aug 2012


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