Impact of neonatal sertraline exposure on the post-myocardial infarction outcomes of adult male mice

Abstract

Neonatal exposure to a selective serotonin reuptake inhibitor (SSRI) leads to decreased left ventricular volumes and sympathetic activation in adult mice. We hypothesized this neonatal SSRI exposure-induced small left heart syndrome would increase post-myocardial infarction (MI) morbidity and mortality. C57BL/6 mice received saline or sertraline (5 mg/kg intraperitoneally) on postnatal days 1-14. At 5 months, male mice underwent coronary artery ligation and were monitored by radiotelemetry until death or 4 weeks after ligation. After ligation, SSRI-exposed mice had increased heart rates (SSRI, 516 ± 13 bpm; control, 470 ± 15 bpm; P < 0.05). SSRI-exposed mice had significant reductions in left ventricular systolic volumes both before and after coronary ligation (SSRI: baseline = 20 ± 3 μL, post-MI = 37 ± 10 μL; control: baseline = 30 ± 3 μL, post-MI = 65 ± 23 μL). Post-MI echocardiography showed significantly decreased ejection fraction in control mice (baseline = 60% ± 4%, post-MI = 41% ± 2%, P < 0.01) but not the SSRI-exposed mice (baseline = 65% ± 3%, post-MI = 53% ± 7%). Neonatal SSRI exposure did not significantly alter post-MI survival. We conclude that the preexisting SSRI-induced small left heart syndrome may provide protection from post-MI ventricular dilation.

Figure 1

Hematoxylin-eosin (A & C) and Masson’s Trichrome (B & D) Staining in neonatal (top row) and adult hearts (bottom row). Stains from control mice are shown in panel A and B and SSRI-exposed mice are shown in panel C and D. Bar = 100 µm.

Figure 2

A–C. Heart rate (A), temperature (B), and activity level (C) recordings over a 30 day period in sertraline exposed mice (black line) and control mice (red line).

Figure 3

Myocardial infarctions following coronary artery ligations in sertraline exposed (top) and control mice (bottom).