Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training

Abstract

Background: Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation.

Methods: Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated.

Results: Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway.

Conclusions: Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation.

Fig 1. Resistance training responses in the maximum load test and the CSA of the Plantaris muscle fiber.

(A) Evolution of maximum load (g) of the C (n = 5) and RT (n = 6) groups during 8 weeks of the RT protocol. Repeated measure ANOVA followed by Duncan’s post hoc. (B) Representative images (40x magnification) of Plantaris muscle fibers stained with HE from the C (n = 5) and RT (n = 6) groups. (C) CSA of Plantaris muscle fiber calculated from the HE-stained posterior sections using Student’s t tests for independent samples. The data are presented as the mean ± standard deviation, significance accepted: p ≤ 0.05. *—Different than the previous maximum load in the same group; ^†—Different than the maximum load in the C group at the same time; ‡—Different from the C group.

Fig 2. Body weight variation throughout 4 days of paradoxical sleep deprivation.

Body weight change (g) of the C (n = 10), RT (n = 10), PSD96 (n = 10), RT/PSD96 (n = 10) groups during 4 days of PSD. The variation was calculated by the equation: current weight—previous weight. Repeated measure ANOVA followed by Duncan’s post hoc. The data are presented as the mean ± standard deviation, significance accepted: p ≤ 0.05. *—Different from the previous body weight in the same group; ^†—Different from the C group at the same time; ^‡—Different from the RT group at the same time; ^x—Different from the PSD96 group at the same time.

Fig 3. Ventricular remodeling, fibrosis and expression of proteins involved in the pathologic cardiac hypertrophy pathway.

Representative images (40x magnification) of HE-stained cross sections (A) of the LV of rats without manipulation (C; n = 6) or submitted to RT (RT; n = 6) or PSD (PSD96; n = 6) or RT followed by PSD (RT/PSD96; n = 6). (B) The images (40x magnification) are the LV tissue sections stained with picrosirius red. Red color stretches are collagen depositions. (C) Images (1.25x magnification) of HE-stained the LV cavity diameter of the heart. (D) Myocyte CSA calculated from the HE-stained sections as shown in A. (E) Histogram showing collagen volume fraction in the LV tissues. (F) Results of the analysis of the LV cavity diameter as shown in C. (G) Quantification of NFATc3 expression. (H) Representative blots of NFATc3, GATA-4 and GAPDH. (I) Quantification of GATA-4 expression. For analysis, we utilized one way ANOVA followed by Duncan’s post hoc. The data are shown as the mean ± standard deviation, significance accepted: p ≤ 0.05. *—Different from the C group; ^†—Different from the RT group; ^‡—Different from the PSD96 group.

Fig 4. Expression of Proteins Involved the Maintenance of Normal Cardiac Ca²⁺ Homeostasis.

(A) Representative blot of RyR and their normalization for total protein and the demonstrative graph of statistical analysis. (B) Representative blot of SERCA2a and their normalization for GAPDH and the demonstrative graph of statistical analysis. (C) Representative blot of phospho-Ser¹⁶-Thr¹⁷-PLN (p.PLN) and their normalization for total PLN and the demonstrative graph of statistical analysis. (D) Representative blot of NCX and their normalization for GAPDH and the demonstrative graph of statistical analysis. For analysis, we utilized one way ANOVA followed by Duncan’s post hoc. The data are shown as the mean ± standard deviation, significance accepted: p ≤ 0.05. *—Different from the C group; ^†—Different from the RT group.

Fig 5. Main echocardiographic variables.

Results of (A) E wave: maximum protodiastolic mitral flow velocity; (B) A wave: maximum telediastolic mitral flow velocity; (C) EDT: E-wave deceleration time; (D) LA: left atrium diameter; (E) LVAWd: diastolic left ventricle anterior wall thickness; (F) LVPWd: diastolic left ventricle posterior wall thickness. Repeated Measure ANOVA with post hoc Duncan Test. The data are presented as the mean ± standard deviation, significance accepted: p ≤ 0.05. N = 10. *—Different from the baseline of the same group; ^†—Different from the C group at the same time; ^‡—Different from the RT at the same time; ^x—Different from the PSD96 group at same time.

Fig 6. Main hemodynamic variables.

Results of (A) LVSP: left ventricular systolic pressure; (B) +dP/dt: maximum positive time derivative of developed pressure; (C) HR: heart rate. One way ANOVA followed by Duncan’s post hoc. The data are presented as the mean ± standard deviation, significance accepted: p ≤ 0.05. N = 10. *—Different from the C group; ^†—Different from the RT group; ^‡—Different from the PSD96 group.