title: Early citalopram treatment increases mortality due to left ventricular rupture in mice after myocardial infarction.
abstract: Both anxiety and depression are common and independent outcome predictors in patients after myocardial infarction (MI). However, it is unclear whether and how anti-depressants influence remodeling after MI. Thus, we studied cardiac remodeling in mice after experimental MI under treatment with citalopram, a selective serotonin reuptake inhibitor widely used as antidepressant.
  
  
  
  Treatment with citalopram versus saline was applied via osmotic pump after coronary artery ligation. Two different groups were studied: early treatment during the healing phase (starting immediately after surgery), or late treatment in the remodeling phase (starting 7days after surgery). Late treatment did not change mortality or left ventricular remodeling after MI over the period of 6weeks. However, in the early treatment group mortality was increased in citalopram-treated mice predominantly due to left ventricle rupture without differences in infarct size. Remodeling 4weeks after MI was not altered by the treatment. Neither infiltration of inflammatory cells, as determined by FACS analysis of myocardial tissue, nor mRNA-expression of inflammatory cytokines changed 3days after MI in the early treatment group. However, extracellular matrix functioning was altered: There was a significant increase of MMP13 in citalopram treated animals after MI. Pretreatment with the MMP inhibitor PD 166793 prevented left ventricular ruptures and demonstrated a tendency to improved survival after citalopram treatment.
  
  
  
  Treatment with antidepressant citalopram in the acute but not in the late phase after MI significantly increased mortality in mice by disturbing early healing. Pharmacological MMP inhibition partially reversed the deleterious effects of citalopram.
authors.affiliation: University Hospital of Würzburg, Medical Clinic and Policlinic I, Würzburg, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany. Electronic address: frey_a@ukw.de.
authors.forename: Anna
authors.initials: A
authors.lastname: Frey
authors.affiliation: University Hospital of Würzburg, Medical Clinic and Policlinic I, Würzburg, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany.
authors.forename: Veronica-Maria
authors.initials: VM
authors.lastname: Saxon
authors.affiliation: University Hospital of Würzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Würzburg, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany.
authors.forename: Sandy
authors.initials: S
authors.lastname: Popp
authors.affiliation: University Hospital of Würzburg, Medical Clinic and Policlinic I, Würzburg, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Lehmann
authors.affiliation: Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Mathes
authors.affiliation: Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Pachel
authors.affiliation: Medical Clinic and Policlinic III, University Hospital of Halle (Saale), Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hofmann
authors.affiliation: University Hospital of Würzburg, Medical Clinic and Policlinic I, Würzburg, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.affiliation: University Hospital of Würzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Würzburg, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.affiliation: Medical Clinic and Policlinic III, University Hospital of Halle (Saale), Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
mesh_terms: D000818:Animals; D001706:Biopsy; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D006342:Heart Rupture, Post-Infarction / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D009026:Mortality; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D061665:Time-to-Treatment; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D015283:Citalopram; D003094:Collagen; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antidepressant; Citalopram; Early healing; Mice; Myocardial infarction; Remodeling