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Bradykinin does not mediate remote ischaemic preconditioning or ischaemia-reperfusion injury in vivo in man.

Research paper by Christian M CM Pedersen, Michael R MR Schmidt, Gareth G Barnes, Hans Erik HE Bøtker, Rajesh K RK Kharbanda, David E DE Newby, Nicholas L NL Cruden

Indexed on: 30 Aug '11Published on: 30 Aug '11Published in: Heart (British Cardiac Society)



Abstract

To 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.Randomised double-blind, cross-over study.Royal Infirmary of Edinburgh, Wellcome Trust Clinical Research Facility.Twenty healthy male volunteers.Subjects 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.Bilateral forearm blood flow was assessed using venous occlusion plethysmography during intra-arterial infusion of acetylcholine (5-20 μg/min).Acetylcholine 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.These 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.NCT00965120 and NCT00965393.