Anna Frey1, Veronica-Maria Saxon2, Sandy Popp3, Marc Lehmann2, Denise Mathes4, Christina Pachel4, Ulrich Hofmann5, Georg Ertl2, Klaus-Peter Lesch3, Stefan Frantz5. 1. 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. 2. University Hospital of Würzburg, Medical Clinic and Policlinic I, Würzburg, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany. 3. University Hospital of Würzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Würzburg, Germany; Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany. 4. Comprehensive Heart Failure Center, University Hospital of Würzburg, Germany. 5. Medical Clinic and Policlinic III, University Hospital of Halle (Saale), Germany.
Abstract
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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: Merry L Lindsey; Roberto Bolli; John M Canty; Xiao-Jun Du; Nikolaos G Frangogiannis; Stefan Frantz; Robert G Gourdie; Jeffrey W Holmes; Steven P Jones; Robert A Kloner; David J Lefer; Ronglih Liao; Elizabeth Murphy; Peipei Ping; Karin Przyklenk; Fabio A Recchia; Lisa Schwartz Longacre; Crystal M Ripplinger; Jennifer E Van Eyk; Gerd Heusch Journal: Am J Physiol Heart Circ Physiol Date: 2018-01-12 Impact factor: 4.733