Chronic fluoxetine reduces autonomic control of cardiac rhythms in rats with congestive heart failure

Abstract

Up to 40% of patients with heart failure develop depression, and depression is an independent risk factor for cardiovascular mortality in this patient population. Consequently, increasing numbers of patients with heart failure are treated with antidepressants. Selective serotonin reuptake inhibitors are typically the antidepressant of choice since this drug class has limited cardiovascular toxicity. However, little is known about the effects of selective serotonin reuptake inhibitors on autonomic cardiac regulation in congestive heart failure (CHF). Here, indexes of cardiac autonomic control were evaluated before and during chronic fluoxetine (FLX) treatment (20 mg·kg(-1)·day(-1), 5 wk) in rats that developed CHF after coronary artery ligation. FLX reduced the low-frequency (LF) component of heart rate variability (HRV; P < 0.01) as well as the sympathetic contribution to LF HRV (P < 0.01) in both CHF and sham-operated rats. Both FLX and CHF reduced high-frequency HRV (P < 0.01). Spontaneous baroreflex gain was decreased in CHF rats 8 wk after ligation (P < 0.01). Cross-spectral coherence between the interbeat interval and mean arterial pressure was reduced in the LF domain 3 wk after ligation in CHF rats (P < 0.01) and was further reduced after chronic FLX treatment (P < 0.01). Plasma catecholamines and LF blood pressure variability were not affected by FLX. Chronotropic responses to both efferent vagal nerve stimulation and isoproterenol administration were reduced in CHF rats and by FLX (P < 0.01), whereas inotropic responses to isoproterenol were reduced only in CHF rats (P < 0.01). These data indicate that chronic FLX reduces the responsiveness to autonomic output controlling cardiac rhythm and may further compromise autonomic regulation of cardiac function in CHF.