title: Inhibition of monoamine oxidase A increases recovery after experimental cardiac arrest.
abstract: OBJECTIVE
  Perioperative myocardial infarction (MI) with ischaemia-reperfusion injury (IRI) is a devastating entity occurring in 1-2% of patients after cardiac surgery. The molecular pathway leading to myocardial cellular destruction after MI may include monoamine oxidases. We experimentally investigated whether moclobemide, a monoamine oxidase inhibitor, enhances myocardial recovery after cardiac arrest and MI.
  
  
  METHODS
  Fifty-six syngeneic Fischer rats underwent heterotopic cardiac transplantation to induce reversible IRI after cardiac arrest. Twenty-eight rats also underwent permanent ligation of the left anterior descending coronary artery to induce MI after cardiac arrest. Twenty-eight rats with or without MI were treated with subcutaneous moclobemide 10 mg/kg/day. Methods used to study myocardial recovery were microdialysis for intramyocardial metabolism, histology and quantitative reverse-transcription polymerase chain reaction for high-mobility group box-1 (HMGB1), haeme oxygenase-1 (HO-1), interleukin-6, hypoxia-inducible factor 1α and macrophages (CD68).
  
  
  RESULTS
  Pyruvate increased in MI treated with moclobemide versus IRI with moclobemide (29.19 ± 7.64 vs 13.86 ± 8.49 µM, P = 0.028), reflecting metabolic activity after cardiac arrest and reperfusion. Myocardial inflammation increased in MI compared with IRI after 1 h (0.80 ± 0.56 vs 0, point score units [PSUs], P = 0.003), but decreased after 5 days in MI treated with moclobemide versus MI alone (0.80 ± 0.83 vs 2.00 ± 0.70, PSU, P = 0.033). Expressions of HMGB1, CD68 and HO-1 decreased in MI treated with moclobemide versus MI alone (1.33 ± 0.20 vs 1.75 ± 0.24, fold changes [FCs], P = 0.028; 5.15 ± 1.10 vs 9.59 ± 2.75, FC, P = 0.050; 10.41 ± 4.17 vs 21.28 ± 10.01, FC, P = 0.047), indicating myocardial recovery and increased cellularity of remote intramyocardial arteries.
  
  
  CONCLUSIONS
  Moclobemide enhances myocardial recovery after cardiac arrest and MI; inhibition of remote myocardial changes may be achieved by targeting treatment against monoamine oxidase.
authors.affiliation: Heart Hospital, Cardiac Research, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Vilma
authors.initials: V
authors.lastname: Vuohelainen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine, Tampere, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Hämäläinen
authors.affiliation: Department of Pathology, Fimlab, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Paavonen
authors.affiliation: Department of Anesthesiology, Intensive Care Unit, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Karlsson
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine, Tampere, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.affiliation: Heart Hospital, Cardiac Research, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland ari.mennander@sydansairaala.fi ari.mennander@pshp.fi.
authors.forename: Ari
authors.initials: A
authors.lastname: Mennander
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006323:Heart Arrest / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D016027:Heart Transplantation; D008026:Ligation; D020912:Moclobemide / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D020127:Recovery of Function; D016042:Transplantation, Heterotopic; D016896:Treatment Outcome
chemical_list: D008996:Monoamine Oxidase Inhibitors; D017382:Reactive Oxygen Species; D008995:Monoamine Oxidase; D020912:Moclobemide
keywords: Cardiac arrest; Monoamine oxidase A inhibition; Myocardial infarct