title: Mangafodipir as a cardioprotective adjunct to reperfusion therapy: a feasibility study in patients with ST-segment elevation myocardial infarction.
abstract: The aim of the present study was to examine the feasibility of applying the catalytic antioxidant mangafodipir [MnDPDP, manganese (Mn) dipyridoxyl diphosphate] as a cardioprotective adjunct to primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation (STE) myocardial infarction (STEMI). Both MnDPDP and a metabolite (Mn dipyridoxyl ethyldiamine) possess properties as mitochondrial superoxide dismutase mimetics and iron chelators, and combat oxidative stress in various tissues and conditions.
  
  
  
  The study tested MnDPDP (n = 10) vs. saline placebo (n = 10), given as a brief intravenous (i.v.) infusion prior to balloon inflation during pPCI in patients with STEMI. Mangafodipir was well tolerated and did not affect heart rate or blood pressure. Despite longer ischaemic time (205 vs. 144 min, P = 0.019) in the MnDPDP group, plasma biomarker releases were identical for the two groups. With placebo vs. MnDPDP, mean STE resolutions were 69.8 vs. 81.9% (P = 0.224) at 6 h and 73.1 vs. 84.3% (P = 0.077) at 48 h. Cardiac magnetic resonance revealed mean infarct sizes of 32.5 vs. 26.2% (P = 0.406) and mean left ventricular (LV) ejection fractions of 41.8 vs. 47.7% (P = 0.617) with placebo vs. MnDPDP. More LV thrombi were detected in placebo hearts (5 of 8) than MnDPDP-treated hearts (1 of 10; P = 0.011).
  
  
  
  Mangafodipir is a safe drug for use as an adjunct to reperfusion therapy. A tendency to benefit of MnDPDP needs confirmation in a larger population. The study revealed important information for the design of a Phase II trial.
authors.affiliation: Department of Internal Medicine, County Council of Jönköping, Ryhov County Hospital, Jönköping SE-551 85, Sweden Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden jan-erik.karlsson@lj.se.
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Karlsson
authors.affiliation: Department of Internal Medicine, County Council of Jönköping, Ryhov County Hospital, Jönköping SE-551 85, Sweden.
authors.forename: Walid
authors.initials: W
authors.lastname: El-Saadi
authors.affiliation: Department of Internal Medicine, County Council of Jönköping, Ryhov County Hospital, Jönköping SE-551 85, Sweden Department of Radiology, County Council of Jönköping, Jönköping, Sweden.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Radiology, County Council of Jönköping, Jönköping, Sweden.
authors.forename: Werner
authors.initials: W
authors.lastname: Puskar
authors.affiliation: Department of Internal Medicine, County Council of Jönköping, Ryhov County Hospital, Jönköping SE-551 85, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Skogvard
authors.affiliation: Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden Department of Clinical Physiology, County Council of Östergötland, Östergötland, Sweden.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Engvall
authors.affiliation: Division of Drug Research, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Andersson
authors.affiliation: Department of Radiology, County Council of Jönköping, Jönköping, Sweden Department of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Maret
authors.affiliation: Division of Drug Research, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden PledPharma AB, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Jynge
mesh_terms: D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012189:Retrospective Studies; D000072657:ST Elevation Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid
keywords: Cardiac reperfusion injury; Mitochondrial superoxide dismutase; Oxidative stress; Primary PCI; STEMI; Small molecular catalytic antioxidants