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OBJECTIVE: 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. DESIGN: Randomised double-blind, cross-over study. SETTINGS: Royal Infirmary of Edinburgh, Wellcome Trust Clinical Research Facility. PATIENTS: Twenty healthy male volunteers. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: Bilateral forearm blood flow was assessed using venous occlusion plethysmography during intra-arterial infusion of acetylcholine (5-20 μg/min). RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION INFORMATION: NCT00965120 and NCT00965393.

Original publication

DOI

10.1136/heartjnl-2011-300323

Type

Journal article

Journal

Heart

Publication Date

11/2011

Volume

97

Pages

1857 - 1861

Keywords

Acetylcholine, Adrenergic beta-Antagonists, Adult, Bradykinin, Bradykinin Receptor Antagonists, Cross-Over Studies, Double-Blind Method, Endothelium, Vascular, Forearm, Hemodynamics, Humans, Infusions, Intravenous, Injections, Intra-Arterial, Ischemic Preconditioning, Male, Myocardial Ischemia, Myocardial Reperfusion Injury, Plethysmography, Prognosis, Reperfusion Injury, Sodium Chloride, Vasodilator Agents