Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

SEX DIFFERENCES IN CARDIAC REMODELING INDUCED BY EARLY POSTNATAL ABDOMINAL AORTA CONSTRICTION IN RATS

J. Hrdlička 1 , V. Olejníčková 1,2 , F. Papoušek 1 , M. Pešková 1 , E. Zabrodská 2 , J. Neckář 1

1 Laboratory of Developmental Cardiology, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; 2 Institute of Anatomy, First Faculty of Medicine, Charles University, Prague, Czech Republic Pressure overload-induced cardiac remodeling leads to changes in myocardial structure and function and it can result in life-threatening arrhythmias and progression of heart failure. Early postnatal abdominal aorta constriction (AAC) is a unique experimental model of gradual pressure overload that can be used for understanding the role of neonatal cardiac plasticity in cardiac remodeling. Here we examine the impact of increased pressure load imposed briefly after the birth on the development of left ventricle (LV) function and geometry in male and female Wistar rats. Newborn pups were subjected to the surgical induction of AAC or sham operation at postnatal day 2 under light ether anesthesia. A silk ligature was tied around the aorta (in the subdiaphragmatic, suprarenal region), and a hypodermic needle of 0.25 mm in outer diameter. In sham-operated littermates that were used as age-matched controls, the aorta was exposed, but not constricted. Cardiac function and geometry were assessed at postnatal days 21 and 90 using echocardiography. Animals were sacrificed and the hearts were harvested for further analysis. At the end of the study, the relative heart weight was higher in females than in males compared to corresponding sham- operated animals (5.23 ± 0.50 vs. 3.61 ± 0.11 mg/g and 4.35 ± 0.40 vs. 2.71 ± 0.06 mg/g, respectively). In adult rats, AAC led to a gradual increase in LV diastolic diameter by 7% in females and 12% in males compared to sham-operated controls. Diastolic LV anterior and posterior wall thicknesses were increased by 12 % and 10 %, respectively in females, and by 33 % and 31 %, respectively in males. LV systolic function (expressed as fractional shortening) at day 21 was decreased in both female and male hearts with AAC compared to sham- operated animals (41.2 ± 2.6 vs. 46.1 ± 1.5 % and 41.8 ± 2.1 vs. 45.7 ± 2.9 %, respectively). Further decrease in fractional shortening was observed at day 90 in males (to 35.2 ± 2.9) but not in females (41.1 ± 3.4 %) with AAC. Our data suggested, that male Wistar rats are more susceptible to AAC-induced cardiomegaly than female rats. This can be partially explained by differences in body growth. However, further investigation should focus on potential sex differences in myocardial structure, conduction system, and metabolic changes.

Keywords: cardiac remodeling, sex differences, neonatal rats

Funding:Supported by the Ministry of Health of the Czech Republic (grant no. NU21J-02-00039).

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