Dimorfismo sexual no modelo de infarto do miocárdio em ratos: aspectos neuroendócrinos e autonômicos cardiovasculares

Abstract

Premenopausal women are less prone to develop cardiovascular diseases than men and this advantage do not persist in postmenopausal women. Thus herein we aimed to investigate the gender difference and the estrogen influence in cardiac function, fluid balance and thyroid status, in Wistar rats subjected to experimental model of myocardial infarction (MI). In the first step, adult male (n = 18) and female (n = 21) rats underwent experimental MI (MIm and MIf,) or sham-operation (ShamM and ShamF) respectively. One and four weeks post-MI rats were placed in metabolic cages, subjected to echocardiography (ECHO), electrocardiography and then euthanized for blood sample collection and tissue collection (heart, lung and liver). In the second step female rats were ovariectomized (n = 24) or continued intact (n = 21), two weeks later they were subjected to MI (MIOVX and MIINT, respectively) or sham operation (ShamOVX and ShamINT). Four weeks post-MI, they were subjected to the same evaluations of the first step, not only the electrocardiography. In the third step, female rats were subjected to ovariectomy and treated with estrogen (E2) (n = 13) or vehicle (n = 22). Two weeks later they underwent experimental MI (MIOVX+E2 and MIOVX+Veh). Four weeks post-MI they were subjected to the same evaluations of the second step. Male infarcted rats developed cardiac dysfunction (shortening fraction, SF, reduction, ~ 70%) and fluid homeostasis changes (sodium intake increasing, ~ 146% and urinary volume reduction, ~55%) earlier than female, in the first week post-MI while female presented these changes (SF reduction, ~28% and sodium intake increasing, ~143%) only in the fourth week and attenuated compared to male. MIM showed reduction in LF/HF ratio (~70%), one week post-MI. And only male rats presented hypothyroidism after MI (T4 ~52% and T3 ~38%, reduction). We also verified reduction in SF (~55%), increasing in LA/Ao ratio (~75%) and changes in fluid balance (sodium intake reduction, ~67% and urinary volume reduction, ~40%) more pronounced in MIOVX than in MIINT. MIOVX group reduced thyroid hormone levels after MI (T3 ~35%). MIOVX+Veh showed more pronounced reduction in SF (~55%) and increasing in LA/Ao ratio (~75%) than the MIOVX+E2 group. The sodium intake reduced in MIOVX+Veh (~67%) and in the urinary volume we verified significant reduction in ShamOVX+Veh and MIOVX+Veh groups compared to ShamOVX+E2 and MIOVX+E2 groups (P < 0.05). Serum T3 reduced significantly (~35%) only in MIOVX+Veh group. The pathophysiological development of heart failure post-MI was attenuated in female compared to male. And female rats subjected to MI presented fluid balance more favorable and related to the less pronounced development of heart failure. Estrogen seems to influence positively the cardiac function and attenuate the dysfunction that occur post-MI. The euthyroid status in female intact do not seems to be determinant to the less pronounced development of heart failure.