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Previous issue date: 2014-06-30 === O sistema circadiano possui proje??es neurais para o Sistema Nervoso
Aut?nomo (SNA), interferindo diretamente na modula??o simp?tico-vagal do sistema
cardiovascular. Perturba??es no sistema circadiano, como por exemplo as mudan?as de
fase no ciclo claro-escuro (CE), tem sido relacionadas ao risco de surgimento de doen?as
cardiovasculares, devido ao aumento do t?nus simp?tico card?aco e redu??o dos intervalos
RR (iRR). Objetivo: Investigar a intera??o entre o Sistema de Temporiza??o
Circadiano e o controle auton?mico card?aco de ratos. Materiais e m?todo: Foram
utilizados 18 ratos Wistar (?; idade=139,9 ? 32,1 dias; peso=219,5 ? 16,2 g), alocados em
tr?s grupos distintos: Controle (GC), Atraso de fase em 6h (GAT) e Avan?o de fase em 6h
(GAV). Foram exclu?dos tr?s animais durante a coleta de dados (GC/GAT/GAV - n=5
cada).Tel?metros foram implantados cirurgicamente em cada animal, para aquisi??o
cont?nua de sinais de eletrocardiograma - ECG (dura??o de 21 dias no GC e 28 dias no
GAT/GAV). Foi estabelecido um ciclo CE 12h:12h, com in?cio do claro ?s 18:00h e in?cio do
escuro ?s 06:00h. Os animais do GC permaneceram no mesmo ciclo durante todo o per?odo
experimental, enquanto que, no 14? dia de registro, o GAT e o GAV foram submetidos a um
atraso e um avan?o em 6h, respectivamente. Durante todo o per?odo experimental,
registrou-se a Atividade Locomotora (AL), a m?dia da Frequ?ncia Card?aca (mFC) e as
vari?veis relacionadas aos iRR [m?dia dos iRR (mRR), SDNN, RMSSD, BF, AF e raz?o
BF/AF]. Todos os dados foram analisados em blocos de 3 e 7 dias, quanto a presen?a de
ritmo circadiano, valores do Cosinor - mesor, amplitude e acrofase (teste t pareado), rela??o
de fase, diferen?as entre claro e escuro (teste t independente), m?dias a cada 30 minutos ao
longo de cada s?rie temporal (ANOVA two way com post hoc de Bonferroni). Os dados do
bloco B1, M1 e M2 do GC serviram como valores de refer?ncia para as compara??es entre
os blocos de an?lise do GAT/GAV. Resultados: Observou-se ritmicidade circadiana nas
vari?veis de AL, mRR e mFC(p<0,01). Verificou-se rela??o de fase entre as vari?veis
mRR/mFC e a AL nos tr?s grupos, sendo menos est?vel no GAV. No GC, n?o foram
encontradas diferen?as significativas entre os blocos, em nenhuma das an?lises(p>0,05).
Nos blocos de 7 dias dos grupos experimentais, verificou-se redu??o significativa de
mRR(p=0,04) e mFC(p=0,03) no GAT, e de AF(p=0,02) no GAV; al?m disso, entre os blocos
de 3 dias, observou-se um aumento significativo de BF/AF(p=0,04) no GAT, bem como das
vari?veis mRR(p=0,03), SDNN(p=0,04), RMSSD(p=0,04), BF(p=0,01) e AF(p=0,02) no GAV.
Constatou-se que as diferen?as entre as m?dias da mRR, mFC e AL nas fases de claro e
escuro n?o foram significativas ap?s as mudan?as de fase em alguns dos blocos analisados
nos grupos experimentais. N?o foram encontrados resultados significativos na compara??o
das vari?veis r?tmicas a cada 30 minutos ao longo de toda a s?rie experimental, exceto pela
diminui??o significativa de mRR no meio da fase do escuro em B2 e no in?cio da fase de
claro em B3 (p<0,01). Conclus?o: os avan?os e atraso de fase (6h) alteraram o controle
auton?mico card?aco nos grupos experimentais atrav?s da redu??o tempor?ria da VFC. Os
avan?os de fase, aparentemente, tiveram maior influ?ncia negativa nesse processo, em
rela??o aos atrasos de fase. === Introduction: The circadian system has neural projections for the Autonomic Nervous System
(ANS), directly interfering with sympathetic-vagal modulation of the cardiovascular system.
Disturbances in the circadian system, such as phase changes in light-dark cycle (LD), has
been related to the risk of development of cardiovascular diseases due to increased
sympathetic tone and reduction o Heart Rate Variability (HRV - RR intervals). Purpose:
Investigate the interaction between Circadian Timing System and cardiac autonomic control
in rats. Materials and methods: We used 18 Wistar rats (?, age = 139.9 ? 32.1 days, weight
= 219.5 ? 16.2 g), divided into three distinct groups: Control (CG), phase delay of 6h (GDe)
and phase advance of 6h (GAd). Three animals were excluded during data collection
(CG/GDe/GAd - n=5). Telemeters were surgically implanted in each animal for continuous
acquisition of electrocardiographic (ECG) signals (duration of 21 days in the CG and 28 days
in GDe/ GAd). A LD cycle was established 12h: 12h, beginning of light at18:00h and dark at
06:00h. The animals remained in the same CG LD cycle throughout the experimental period,
while, on the 14th day of registration, the GDe and GAd underwent a delay and an advance
in 6h, respectively. Throughout the experimental period, the locomotor activity (LA), the
mean heart rate (mHR) and variables related to iRR [mean RR (mRR), SDNN, RMSSD, LF,
HF and LF/ HF ratio ] were recorded. All data were analyzed in blocks of 3 and 7 days, for
the presence of circadian rhythm, values of Cosinor - mesor, amplitude and acrophase
(paired t test), phase relationship, differences between light and dark (t test independent),
averages every 30 minutes along each time series (two-way ANOVA with post hoc
Bonferroni). The data block B1,M1 and M2 in CG served as benchmarks for comparisons
between series of analysis of the GAT/GAV. Results: We observed circadian rhythmicity in
the variables LA, mRR and mFC(p<0.01). mRR and mFC showed phase relationship with the
LA in all three groups, being less stable in GAd. In the CG, no significant differences
between blocks were found in any of the analyzes(p>0.05). Among the 7 day blocks, there
was a significant reduction in mRR(p=0.04) and mFC(p=0.03) in GDe and significant
reduction in HF mean(p=0.02) in GAd; and between 3 day blocks, a significant increase of
LF/HF(p= 0.04) in the GDe; besides mRR(p=0.03), SDNN(p=0.04), RMSSD (p=0.04), LF
(p=0.01) and HF(p=0.02) significant increase in the GAd. It was found that the differences
between the means of the mRR, LA and mFC in light and dark phases were not significant
after phase changes in some of the blocks/moments (GDe and GAd). No significant results
were found when comparing rhythmic variables means every 30 minutes over the blocks,
except for a significant decrease in mRR at the middle of the dark phase (B2) and the start of
light phase (B3) - (p<0.01). Conclusion: phase advances and delays (6h) altered cardiac
autonomic control in the experimental groups by temporarily HRV decrease. Phase
advances apparently had greater negative interference in this process, in relation to the
phase delays.
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