Effects of fluoxetine on cardiac remodeling and autonomic control of blood pressure and heart rate after myocardial infarction in mice

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are used to treat mental depression after myocardial infarction (MI). It is unknown if SSRIs influence cardiac remodeling after MI. SSRIs may modulate cell proliferation and modify autonomic tone by inhibiting the reuptake of catecholamines. We examined the effects of 2 weeks fluoxetine (FLU) treatment (6 mg/kg.day) on cardiac remodeling in male Swiss mice subjected to coronary artery ligation. 11 days after MI, catheters were implanted and 2 days later blood pressure variability (BPV) and heart rate variability (BPV) were measured (by spectral analysis) in the conscious state as an index of autonomic tone. Compared to non‐treated MI mice, FLU treatment did not alter infarct size, cardiac hypertrophy and cardiac hyperplasia (assessed by BrdU labeling). Basal BP and HR were not altered by FLU treatment. In the absence of treatment low‐frequency BPV and HRV (0.1–1 Hz) were lower in MI than in sham‐MI mice. FLU treatment reduced low‐frequency BPV and HRV in sham and MI mice, reaching values comparable to those observed in non‐treated MI mice. All between group differences in BPV and HRV were eliminated after acute pharmacological blockade with atropine and metoprolol. These data indicate that, in mice, FLU treatment does not aversely modify cardiac remodeling after MI and is associated with a sympatholytic effect.