Journal article
Sertraline exposure leads to small left heart syndrome in adult mice
Pediatric research, Vol.73(3), pp.286-293
03/2013
DOI: 10.1038/pr.2012.183
PMCID: PMC3607080
PMID: 23232669
Abstract
Background: Sertraline, a selective serotonin reuptake inhibitor (SSRI), is the most commonly prescribed therapy for maternal depression. Epidemiologic studies have linked SSRI exposure with decreased fetal growth, altered autonomic regulation, and cardiac malformations. We hypothesized that SSRI exposure decreases left-ventricular (LV) volumes and increases adult sympathetic nervous system activation, resulting in increased adult heart rates.
Methods: C57BL/6 mice received saline or sertraline (5 or 15 mg/kg/day i.p.) on postnatal days 1-14. Adult phenotypes were assessed at 5 mo.
Results: Sertraline-exposed mice had smaller LV internal diameters in diastole (control 4.0 ± 0.1 mm, SSRI 3.7 ± 0.1 mm, P < 0.05), decreased stroke volumes (control 46 ± 2.6 µl, SSRI 37 ± 2.3 µl, P < 0.05), higher heart rates (control 530 ± 13 beats per minute (bpm), SSRI 567 ± 6 bpm, P <0.05), and increased urinary excretion of noradrenaline (control 174 ± 29.4 ng/ml, SSRI 276 ± 35.1 ng/ml, P < 0.05). These changes were associated with increased cerebral serotonin transporter (5-HTT) expression.
Conclusion: Neonatal sertraline exposure causes long-term changes in cardiac morphology and physiology. We speculate that early-life SSRI exposure impairs cardiomyocyte growth and central serotonin signaling, leading to a small left heart syndrome in adult mice.
Details
- Title: Subtitle
- Sertraline exposure leads to small left heart syndrome in adult mice
- Creators
- Sarah E Haskell - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242Gregory M Hermann - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242Benjamin E Reinking - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242Kenneth A Volk - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242Veronica A Peotta - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242Vivian Zhu - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242Robert D Roghair - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Pediatric research, Vol.73(3), pp.286-293
- DOI
- 10.1038/pr.2012.183
- PMID
- 23232669
- PMCID
- PMC3607080
- ISSN
- 0031-3998
- eISSN
- 1530-0447
- Language
- English
- Date published
- 03/2013
- Academic Unit
- Critical Care; Cardiology; Stead Family Department of Pediatrics; Neonatology; Internal Medicine
- Record Identifier
- 9984093231602771
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