title: Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice.
abstract: BACKGROUND
  We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI). In comparison with such a chronic effect, however, the acute effect of donepezil during an acute phase of MI remains unclear. Noticing recent findings of a cholinergic mechanism for anti-inflammatory actions, we tested the hypothesis that donepezil attenuates an acute inflammatory tissue injury following MI.
  
  
  RESULTS
  In isolated and activated macrophages, donepezil significantly reduced intra- and extracellular matrix metalloproteinase-9 (MMP-9). In mice with MI, despite the comparable values of heart rate and blood pressure, the donepezil-treated group showed a significantly lower incidence of cardiac rupture than the untreated group during the acute phase of MI. Immunohistochemistry revealed that MMP-9 was localized at the infarct area where a large number of inflammatory cells including macrophages infiltrated, and the expression and the enzymatic activity of MMP-9 at the left ventricular infarct area was significantly reduced in the donepezil-treated group.
  
  
  CONCLUSIONS
  The present study suggests that donepezil inhibits the MMP-9-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduces the risk of left ventricular free wall rupture during the acute phase of MI.
authors.affiliation: Department of Cardiovascular Control, Kochi Medical School, Nankoku, Kochi, Japan. marikawa@kochi-u.ac.jp
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Arikawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kakinuma
authors.forename: Takemi
authors.initials: T
authors.lastname: Handa
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Yamasaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sato
mesh_terms: D000544:Alzheimer Disease / Q000517:prevention & control; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D000077265:Donepezil; D004591:Electrophoresis, Polyacrylamide Gel; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006342:Heart Rupture, Post-Infarction / Q000517:prevention & control*; D006801:Humans; D007150:Immunohistochemistry; D007189:Indans / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D020780:Matrix Metalloproteinase 9