Abstract

Preeclampsia (PE) is a disorder prevalent in 3-8% of pregnancies, characterized by maternal hypertension and endothelial dysfunction. More recently, it has been shown that preeclamptic women exhibit cardiac dysfunction, impaired global longitudinal strain (GLS), which is indicator of contractility and tissue injury, and increased circulating cardiac troponin I (cTnI), however the underlying mechanisms have not been well studied. The Reduced Uterine Perfusion Pressure (RUPP) model of placental ischemia mimics a PE-like phenotype, including hypertension, endothelial dysfunction and adverse cardiac remodeling. However, whether adverse remodeling translates to impaired cardiac function is not known. The aim of this study was to assess cardiac function in RUPP rats during pregnancy. We tested the hypothesis that placental ischemia in the RUPP rat leads to impaired left ventricular (LV) systolic function and GLS. To address this, all animals underwent comprehensive echocardiography assessment on gestational day (GD) 14. RUPP rats underwent surgery to place silver clips on the abdominal aorta and branches of the ovarian artery to induce placental ischemia. Both the Sham ( n =10) and RUPP ( n =10) rats had indwelling carotid catheters placed on GD 18, and blood pressure and echocardiography measurements were made on GD 19. The RUPP group showed significantly increased mean arterial pressure compared to the Sham group on GD 19 (123 ± 3 vs. 97 ± 2 mmHg, P<0.01). RUPP hearts also showed reductions in LV ejection fraction (60 ± 2 vs. 78 ± 2 %, P<0.01) and fractional shortening (46 ± 3 vs. 56 ± 1 %, P=0.05), in addition to cardiac hypertrophy (0.97 ± 0.04 vs.0.91 ± 0.02 g, P=0.02). GLS was decreased in the RUPP group compared to the Sham (-17.89 ± 0.5 vs. -26.31 ± 2.7 %, P=0.02), suggesting impaired contractility and injury, and these data were accompanied by increased circulating cTnI. In conclusion, cardiac dysfunction and impaired cardiac strain is present in the RUPP rat in response to placental ischemia. The implication of these findings is the use of an appropriate animal model to understand the mechanisms of cardiac dysfunction in PE and potentially develop therapeutic options that improve cardiac abnormalities in these patients.

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