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Dimorfismo sexual no modelo de infarto do mioc?rdio em ratos: aspectos neuroend?crinos e auton?micos cardiovasculares / Sexual dimorphism in the myocardial infarction model in rats: neuroendocrine and autonomic cardiovascular aspectsSouza, Natalia Soares Carvalho de 26 August 2014 (has links)
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Previous issue date: 2014-08-26 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / 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 / Sabe-se que mulheres na pr?-menopausa apresentam menor preval?ncia de doen?as
cardiovasculares do que homens e, esta diferen?a desaparece ap?s a menopausa. Sendo
assim, o presente estudo buscou avaliar o dimorfismo sexual e a influ?ncia do estr?geno
nas altera??es da fun??o card?aca, do equil?brio hidroeletrol?tico e do status tireoidiano
de ratos Wistar submetidos ao infarto do mioc?rdio (IM) experimental.
Na primeira etapa ratos wistar machos (n = 18) e f?meas (n = 21) foram submetidos ao
infarto experimental (INF.M e INF.F) ou ? falsa cirurgia (Sham.M e Sham.F). Na
primeira e quarta semana p?s-IM foram colocados em gaiolas metab?licas e submetidos
? ecodopplercardiografia (ECO) e eletrocardiografia (an?lise espectral), seguido de
eutan?sia para coleta de sangue (dosagem s?rica de horm?nios tireoidianos) e de tecidos
(cora??o, pulm?o e f?gado, para biometria). Na segunda etapa, f?meas foram
ovariectomizadas (n = 24) ou mantidas intactas (n = 21) e ap?s duas semanas
submetidas ao infarto do mioc?rdio (INFOVX e INFINT) ou ? falsa cirurgia (ShamOVX e
ShamINT). Quatro semanas ap?s p?s-IM, as mesmas avalia??es da etapa anterior foram
realizadas exceto a eletrocardiogr?fica. Na terceira etapa, foi realizada ovariectomia e
reposi??o com estr?geno (E2) ( n = 13) ou ve?culo (n = 22). Ap?s duas semanas foi
realizada a cirurgia de indu??o ao infarto (INFOVX+E2 e INFOVX+Veic) e a falsa cirurgia
(ShamOVX+E2 e ShamOVX+Veic). Decorridas quatro semanas foram feitas as mesmas
avalia??es da segunda etapa.
O grupo INFM desenvolveu disfun??o card?aca (fra??o de encurtamento, FEnc%, ~70%
de redu??o) e altera??es na regula??o hidroeletrol?tica (aumento do apetite por s?dio,
~146% e redu??o do volume urin?rio, ~55%), uma semana p?s-IM e, portanto, mais
cedo que as f?meas, que apresentaram altera??es na fun??o card?aca (FEnc%, ~28% de
redu??o) e regula??o hidroeletrol?tica (aumento do apetite por s?dio, ~143%) na quarta
semana p?s-IM. O grupo INFM apresentou redu??o na rela??o LF/HF (~70%), uma
semana p?s-IM. E, apenas os ratos machos desenvolveram hipotireoidismo ap?s o
infarto. Tamb?m foi observada redu??o da FEnc% (~55%), aumento da rela??o ?trio
esquerdo/ aorta (AE/Ao, ~75%) e altera??es na regula??o hidroeletrol?tica (redu??o do
apetite por s?dio, ~67% e do volume urin?rio, ~40%) mais pronunciadas em INFOVX do
que em INFINT. O grupo INFOVX tamb?m apresentou redu??o dos n?veis s?ricos de T3
(~35%) p?s-IM. O grupo INFOVX+Vei mostrou redu??o da FEnc% (~55%) e aumento na
rela??o AE/Ao (~75%) mais pronunciadas que o grupo INFOVX+E2. INFOVX+Vei reduziu o
apetite por s?dio (~67%) e, no volume urin?rio, foi observada redu??o significativa nos
grupos ShamOVX+Vei e INFOVX+Vei em rela??o aos grupos ShamOVX+E2 e INFOVX+E2
(P<0,05). O T3 s?rico reduziu significativamente (~35%) apenas no grupo INFOVX+Vei.
Houve diferen?a no desenvolvimento fisiopatol?gico da insufici?ncia card?aca (IC) p?s-
IM entre machos e f?meas, sendo mais brando nas f?meas. E f?meas infartadas
apresentaram uma regula??o hidroeletrol?tica mais favor?vel e compat?vel com o
desenvolvimento menos acentuado da IC. O estr?geno influenciou positivamente a
regula??o hidroeletrolitica de f?meas infartadas, o que favoreceu a fun??o card?aca e
atenuou desta forma, a disfun??o que ocorre ap?s o infarto. A manuten??o do status
eutire?ideo n?o pareceu ser determinante para o desenvolvimento menos pronunciado
da IC
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