Effect of Depression and Sertraline Treatment on Cardiac Function in Female Nonhuman Primates

Abstract

Objective Depression is a proposed risk factor for heart failure based largely on epidemiological data; little experimental data is available addressing this hypothesis. Methods Depression was evaluated in relation to cardiac structural and functional phenotypes assessed by transthoracic echocardiography in 42 adult female cynomolgus monkeys that consumed a Western-like diet for 3 years. Half of the monkeys were treated with the SSRI sertraline HCl for 18 months and depressive behavior was assessed for 12 months prior to echocardiography. Results Depressed monkeys (the 19/42 with depressive behavior rates above the mean rate) had higher HRs (171±4.1 vs 152±6.1), and smaller BSA (0.13±0.003 vs 0.15±0.004). Cardiac measures showed lower LV end systolic dimension (0.75±0.05 vs 0.89±0.04), LV systolic (0.76±0.08 vs 1.2±0.11) and diastolic (2.4±0.23 vs 3.4±0.26) volumes, and left atrial volumes (1.15±0.14 vs 1.75±0.12) in depressed versus nondepressed monkeys (p’s <0.05). Doppler profiles of depressed monkeys indicated greater myocardial relaxation (higher e′ and higher e′/a′ ratio) and lower filling pressures (lower E/e′) compared to nondepressed monkeys (p’s<0.05). Although treatment with sertraline reduced HR (150±5.8 vs 171±4.8) and modestly increased chamber dimensions (left ventricular end systolic dimension: 0.91±0.05 vs 0.74±0.03; left ventricular end diastolic dimension, BSA adjusted 1.69±0.05 vs 1.47±0.06) (p’s<0.05), it did not overtly affect systolic or diastolic function (p’s >0.10). Conclusions These data suggest that behavioral depression in female primates is accompanied by differences in cardiac function, although not in ways classically associated with subclinical heart failure. SSRIs show promise in supporting heart function by reducing HR and perhaps improving LV filling, however further investigation is needed to confirm this hypothesis.

Long-term sertraline treatment and depression effects on carotid artery atherosclerosis in premenopausal female primates

“…Sertraline HCl (Zoloft ® ) was chosen due to the need to dose monkeys according to body weight and its lack of effect on body weight in macaques 38 . We have previously published that there were no differences between treatment groups in cardiac function 36 cardiovascular risk factors 34, 37 , or illiac artery atherosclerosis 34 prior to randomization. Monkeys were treated daily for 18 months.…”

“…Details about the animals; diets and methods used to evaluate circulating sertraline and desmethylsertraline concentrations, 35 , cardiac function 36 cardiovascular risk factors 34,37 , and coronary artery atherosclerosis 34 have been published previously. Briefly, forty-five reproductively-aged female cynomolgus were imported from Indonesia (Institut, Pertanian Bogor, Bogor, Indonesia) and quarantined in single cages for a one-month.…”

“…Anthropometrics and body composition, lipid metabolism, ovarian function, heart rate, 34 cardiac structure/function 36 , carbohydrate metabolism, adiponectin, and physical activity 37 were assessed using previously described methods. Briefly, body weight (BW), body mass index (BMI), body composition, fasting insulin and glucose, and adipocytokines were measured prior to and at the end of the treatment phase.…”

“…37 Transthoracic echocardiography was performed 14 months after the onset of the treatment phase, following ketamine (15mg/kg) sedation. 36 Fasting total plasma cholesterol (TPC), high-density lipoprotein cholesterol (HDLC), triglycerides concentrations were measured after 0, 3, 10, and 17 months of treatment, the ratio of TPC/HDLC was determined at each timepoint, and averaged across the treatment phase. Ovarian function was determined over the course of one-year during the pretreatment and treatment phases by vaginal swabbing to detect menses.…”

“…41–43 Aortic velocity time integral (AO-VTI) and eft ventricular end internal diastolic dimension (LV-IDD) was measured by Doppler echocardiography at the end of the treatment phase. 36 Indirect blood pressure (BP) was measured at the end of the treatment phase using High Definition Oscillometry (Vetline LLC, Saint Kitts and Nevis). Average BP (systolic and diastolic) were averaged from three measurements, taken 40-seconds apart an average of 12.5 minutes post- ketamine sedation.…”