Congenital hypothyroidism is associated with structural and functional heart alterations in male Sprague-Daeley rats during adulthood

E MARTINEZ; NAVARRO, MÓNICA PAULA; FELLET, ANDREA

MAR DEL PLATA

Congreso; REUNIÓN ANUAL CONJUNTA SAIC SAI FAIC; 2022

SOCIEDAD ARGENTINA DE INVESTIGACION CLINICA, SAIC.

The thyroid hormones are detectable in the fetal circulation from early in gestation and have important have significant impacts on development, metabolism, and maturation in the fetus. The fetus´ ability to grow and adapt to extrauterine life is compromised by thyroid hormone deficiency during intrauterine development. It is well known that in mammals many tissues are not completely developed at birth, which means that the pattern of expression of many genes is not entirely completed. So, the neonatal period is an important stage of life in which hormonal, neuronal and metabolic disturbances may influence the program of expression of some gene in the adult life. We previously showed that perinatal hypothyroidism altered myocardial contractility in young and adult rats. The goal of this study is to investigate whether congenital hypothyroidism induced by methimazole during three different stages of life (intrauterine period, lactation and perinatal) would affect the growth of animals as well as cardiac function. In this study, pregnant rats were divided in three groups: Group G (free access to water containing 0,02% (w/v) methimazole from day 9 until parturition), Group GL (free access to water containing 0,02% (w/v) methimazole from day 9 until 21 days after parturition), Group C (free access to water no containing 0,02% (w/v) methimazole during all experimental time). Methimazole treatment started on day 9 after copulation because it was just before testis differentiation period and also, because it has been shown that exposure to methimazole prior to day 9 post copulation resulted in fetal loss. All male pups had free access to pelleted rodent chow and tap water and maintained in groups of up to three/cage until 90 days. We made additional group hypo (male Sprague–Dawley rats weighing approximately 50 g received 0.02% methimazole in drinking water for 90 days). Treatment efficacy was determined by measuring thyroid-stimulating hormone (TSH), total triiodothyronine (T3) and thyroxin (T4) using radioimmunoassay at the beginning and the end of the experimental period. During all this time, systolic arterial pressure, body mass, length of tibia and tail were evaluated. After 90 days, left ventricular function was evaluated by echocardiography left ventricle internal diameter (LVID), left ventricle posterior wall thickness (PWT) and anterior wall thickness (AWT) were measured in both systole (s) and diastole (d). Ejection fraction (EF), fractional shortening (FS) and systolic volume were measured from ventricular internal diameters by the echocardiography system. All determinations were made according to the guidelines of the American Society of Echocardiography. GL group showed a decrease in FS (%, GL: 49±6* vs. C: 65±16), similar to the observed in hypo group (%, hypo: 47±3* vs. C: 65±16). There was no significant difference between group G and group C. Similarly, GL and hypo animals presented lowered EF (%, GL: 79±6*, hypo: 83±2* vs. C: 89±9). Conversely, no difference was found between GL and C groups regarding AWT in both systole and diastole. AWT was diminished in systole and diastole in groups G and hypo (AWTs, mm, G: 2,9±0,6*, hypo: 2,5±0,7* vs. C: 3,8±0,6; AWTd, mm, G: 1,5±0,5*, hypo: 1,4±0,5* vs. C: 1,9±0,3). When analyzing PWT, only hypo group presented lowered results in systole and diastole (PWTs, mm, hypo: 2,5±0,4* vs. C: 3,8±0,6; PWTd, mm, hypo: 1,5±0,2* vs. C: 2,5±0,33). Groups GL and hypo showed an increase in the LVID in systole and diastole (LVIDs, mm, GL: 3,5±0,6*, hypo: 2,87±0,1* vs. C: 1,8±0,1; LVIDd, mm, GL: 6,9±0,5*, hypo: 6,0±0,2* vs. C: 5,2±0,2).*P