title: Cardioprotective effects of the MR contrast agent MnDPDP and its metabolite MnPLED upon reperfusion of the ischemic porcine myocardium.
abstract: OBJECTIVE
  To evaluate whether manganese dipyridoxyl diphosphate (MnDPDP) or its metabolite manganese dipyridoxyl ethyldiamine (MnPLED) reduces post-ischemic myocardial injury.
  
  
  METHODS
  Left anterior descending artery (LAD) in anesthetized pigs was occluded (30 min) followed by reperfusion (120 min) during hemodynamic monitoring and infarct assessment. Three micromol/kg MnDPDP, 1 micromol/kg MnPLED (or a mixture of both) or saline was injected i.v. 10 min before reperfusion followed by infusion of either 3 micromol/kg/h MnDPDP, 1 micromol/kg/h MnPLED (or a mixture of both) or saline. The plasma concentrations of MnDPDP, MnPLED and other metabolites (e.g., ZnDPDP and ZnPLED) were analyzed.
  
  
  RESULTS
  Femoral blood flow was reduced by 60% during early reperfusion in controls, whereas only 23 and 31% reductions were seen in animals treated with MnDPDP and MnPLED. During that time, +LV/dP and -LV/dP (maximum rate of left ventricular isovolumic contraction and relaxation, respectively), systolic pressure and diastolic pressure fell significantly less in animals treated with MnDPDP or MnPLED. Three out of 5 control animals experienced ventricular fibrillation (VF) during reperfusion, whereas VF was not seen in any of the pigs treated with MnPLED or/and MnDPDP. The infarct sizes in saline- and MnPLED-treated animals were 39+/-6 and 16+/-5%, respectively, of the occluded areas. MnDPDP did not reduce the infarct size. A mixture of MnDPDP and MnPLED significantly reduced infarct size (10+/-4%). When reperfusion started and throughout reperfusion, almost all injected MnDPDP was present as Zn-metabolites.
  
  
  CONCLUSIONS
  MnPLED seems to reduce reperfusion-induced cardiac dysfunction and infarct size in pigs. MnDPDP does not reduce infarct size in the pig, probably because of the rapid exchange of Mn2+ for Zn2+ taking place in the pig.
authors.affiliation: Department of Pharmacology, Linköping University, Linköping, Sweden.
authors.forename: J O
authors.initials: JO
authors.lastname: Karlsson
authors.forename: H
authors.initials: H
authors.lastname: Brurok
authors.forename: M
authors.initials: M
authors.lastname: Eriksen
authors.forename: R
authors.initials: R
authors.lastname: Towart
authors.forename: K G
authors.initials: KG
authors.lastname: Toft
authors.forename: O
authors.initials: O
authors.lastname: Moen
authors.forename: B
authors.initials: B
authors.lastname: Engebretsen
authors.forename: P
authors.initials: P
authors.lastname: Jynge
authors.forename: H
authors.initials: H
authors.lastname: Refsum
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003287:Contrast Media / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D013552:Swine
chemical_list: D002316:Cardiotonic Agents; D003287:Contrast Media; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid