title: Rotigaptide protects the myocardium and arterial vasculature from ischaemia reperfusion injury.
abstract: Ischaemia-reperfusion injury (IRI) causes impaired endothelial function and is a major component of the adverse effects of reperfusion following myocardial infarction. Rotigaptide increases gap junction conductance via connexin-43. We tested the hypothesis that rotigaptide reduces experimental myocardial infarction size and ameliorates endothelial IRI in humans.
  
  
  
  Myocardial infarction study: porcine myocardial infarction was achieved by catheter-induced occlusion of the left anterior descending artery. In a randomized double-blind study, rotigaptide (n = 9) or placebo (n = 10) was administered intravenously as a 10 min bolus prior to reperfusion and continuously during 2 h of reperfusion. Myocardial infarction size (IS) was assessed as proportion of the area at risk (AAR). Human translational study: forearm IRI was induced in the presence or absence of intra-arterial rotigaptide. In a randomized double-blind study, forearm arterial blood flow was measured at rest and during intra-arterial infusion of acetylcholine (5-20 μg min(-1) ; n = 11) or sodium nitroprusside (2-8 mg min(-1) ; n = 10) before and after intra-arterial infusion of placebo or rotigaptide, and again following IRI.
  
  
  
  Myocardial infarction study: Rotigaptide treatment was associated with a reduction of infarct size (IS/AAR[%]: 18.7 ± 4.1 [rotigaptide] vs. 43.6 ± 4.2 [placebo], P = 0.006). Human translational study: Endothelium-dependent vasodilatation to acetylcholine was attenuated after ischaemia-reperfusion in the presence of placebo (P = 0.007), but not in the presence of rotigaptide (P = NS). Endothelium-independent vasodilatation evoked by sodium nitroprusside was unaffected by IRI or rotigaptide (P = NS).
  
  
  
  Rotigaptide reduces myocardial infarction size in a porcine model and protects from IRI-related endothelial dysfunction in man. Rotigaptide may have therapeutic potential in the treatment of myocardial infarction.
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.|Department of Cardiology, Aarhus University Hospital Skejby, Aarhus.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Pedersen
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Sowmya
authors.initials: S
authors.lastname: Venkatasubramanian
authors.affiliation: Department of Cardiology, Aarhus University Hospital Skejby, Aarhus.
authors.forename: Henrik
authors.initials: H
authors.lastname: Vase
authors.affiliation: Department of Anaesthesia and Intensive Care, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Janus A
authors.initials: JA
authors.lastname: Hyldebrandt
authors.affiliation: Oxford NIHR Biomedical Research Centre, The John Radcliffe Hospital, Oxford.
authors.forename: Hussain
authors.initials: H
authors.lastname: Contractor
authors.affiliation: Department of Cardiology, Aarhus University Hospital Skejby, Aarhus.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schmidt
authors.affiliation: Department of Cardiology, Aarhus University Hospital Skejby, Aarhus.
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Cruden
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: Oxford NIHR Biomedical Research Centre, The John Radcliffe Hospital, Oxford.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Kharbanda
authors.affiliation: Institute for Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK.
authors.forename: Ninian N
authors.initials: NN
authors.lastname: Lang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009599:Nitroprusside / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009842:Oligopeptides; D020011:Protective Agents; D009599:Nitroprusside; C477643:rotigaptide; D000109:Acetylcholine
keywords: blood flow; endothelium; myocardial infarction; pharmacology; reperfusion