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Randomized Controlled Trial
Bradykinin does not mediate remote ischaemic preconditioning or ischaemia-reperfusion injury in vivo in man.
- Christian M Pedersen, Michael R Schmidt, Gareth Barnes, Hans Erik Bøtker, Rajesh K Kharbanda, David E Newby, and Nicholas L Cruden.
- Centre for Cardiovascular Science, University of Edinburgh, UK. christian.m.pedersen@ki.au.dk
- Heart. 2011 Nov 1; 97 (22): 1857-61.
ObjectiveTo examine whether endogenous bradykinin mediates the endothelium-dependent vasomotor dysfunction induced by ischaemia-reperfusion injury, or the protection afforded by remote ischaemic preconditioning in vivo in man.DesignRandomised double-blind, cross-over study.SettingsRoyal Infirmary of Edinburgh, Wellcome Trust Clinical Research Facility.PatientsTwenty healthy male volunteers.InterventionsSubjects were randomised to intravenous infusion of the bradykinin B(2) receptor antagonist, HOE-140 (100 μg/kg), or saline placebo in a double-blind, crossover trial. Ischaemia-reperfusion injury was induced in the non-dominant arm by inflating a cuff to 200 mm Hg for 20 min in all subjects. Ischaemia-reperfusion injury was preceded by three cycles of remote ischaemic preconditioning in the dominant arm in 10 subjects.Main Outcome MeasuresBilateral forearm blood flow was assessed using venous occlusion plethysmography during intra-arterial infusion of acetylcholine (5-20 μg/min).ResultsAcetylcholine caused vasodilatation in all studies (p<0.05) that was attenuated by ischaemia-reperfusion injury, both in the presence (p=0.0002) and absence (p=0.04) of HOE-140. Remote ischaemic preconditioning abolished the impairment of endothelium-dependent vasomotor function induced by ischaemia-reperfusion injury. HOE-140 had no effect on the protection afforded by remote ischaemic preconditioning.ConclusionsThese findings do not support a major role for endogenous bradykinin, acting via the B(2) kinin receptor, in the mechanism of ischaemia-reperfusion injury or the protective effects of remote ischaemic preconditioning in man.Clinical Trial Registration InformationNCT00965120 and NCT00965393.
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