Pregnancy restores altered sympathetic vasomotor modulation and parasympathetic cardiac modulation in hypertensive rats.

Hypertension is associated to impaired baroreflex sensitivity (BRS). In spontaneously hypertensive rats (SHR), pregnancy reduces blood pressure, and this effect has been associated to increase nitric oxide (NO) bioavailability. Increased NO bioavailability has been linked to improve BRS in hypertensive animals. Therefore, we hypothesize that pregnancy improves the BRS in SHR. We performed experiments to evaluate the vasomotor and cardiac autonomic modulation, also to evaluate the BRS at baseline conditions (spontaneous) and after phenylephrine (PE) and sodium nitroprusside (SNP) administrations in non-pregnant (NP) and pregnant (P) Wistar rats and SHR. Beat-to-beat time series with systolic arterial pressure values were generated and processed by Fast Fourier Transform (spectral analysis). Next, spectra were integrated into low-frequency (LF) band and had their power taken as an index of sympathetic modulation on arterial pressure. Reduced mean arterial pressure was observed in P-groups when compared to NP matched rats, although we did not observe alterations in heart rate (HR). In SHR-NP, spectral analysis revealed altered cardiovascular autonomic modulation when compared to the other groups. However, in SHR-P the autonomic parameters were similar to those observed in Wistar-NP, suggesting that pregnancy changed autonomic modulation. BRS assessed by means of the sequence method was found similar in P-groups. Pregnancy reduced the BRS during hypotension in Wistar. BRS assessed with PE and SNP administration was found lower in SHR-NP as compared to Wistar-NP, and it was not altered by pregnancy. In conclusion, pregnancy did not improve the BRS in SHR, but normalized altered sympathetic vasomotor modulation in SHR.

Physiological Sympathetic Activation Reduces Systemic Inflammation: Role of Baroreflex and Chemoreflex.

Baroreflex and chemoreflex act through the autonomic nervous system, which is involved with the neural regulation of inflammation. The present study reports the effects of reflex physiological sympathetic activation in endotoxemic rats using bilateral carotid occlusion (BCO), a physiological approach involving the baroreflex and chemoreflex mechanisms and the influence of the baroreceptors and peripheral chemoreceptors in the cardiovascular and systemic inflammatory responses. After lipopolysaccharide (LPS) administration, the arterial pressure was recorded during 360 min in unanesthetized rats, and serial blood samples were collected to analyze the plasma cytokine levels. BCO elicited the reflex activation of the sympathetic nervous system, providing the following outcomes: (I) increased the power of the low-frequency band in the spectrum of the systolic arterial pressure during the BCO period; (II) reduced the levels of pro-inflammatory cytokines in plasma, including the tumor necrosis factor (TNF) and the interleukin (IL)-1ß; (III) increased the plasma levels of anti-inflammatory cytokine IL-10, 90 min after LPS administration. Moreover, selective baroreceptor or chemoreceptor denervation deactivated mechanosensitive and chemical sensors, respectively, and decreased the release of the LPS-induced cytokine but did not alter the BCO modulatory effects. These results show, for the first time, that physiological reflex activation of the sympathetic circuit decreases the inflammatory response in endotoxemic rats and suggest a novel function for the baroreceptors as immunosensors during the systemic inflammation.

Electrical stimulation of the carotid sinus lowers arterial pressure and improves heart rate variability in L-NAME hypertensive conscious rats.

We evaluated the effects of long-term (48 h) electrical stimulation of the carotid sinus (CS) in hypertensive rats. L-NAME-treated (10 days) Wistar rats were implanted with a catheter in the femoral artery and a miniaturized electrical stimulator attached to electrodes positioned around the left CS, encompassing the CS nerve. One day after implantation, arterial pressure (AP) was directly recorded in conscious animals for 60 min. Square pulses (1 ms, 3 V, 30 Hz) were applied intermittently (20/20 s ON/OFF) to the CS for 48 h. After the end of stimulation, AP was recorded again. Nonstimulated rats (control group) and rats without electrodes around the CS (sham-operated) were also studied. Next, the animals were decapitated, and segments of mesenteric resistance arteries were removed to study vascular function. After the stimulation period, AP was 16 ± 5 mmHg lower in the stimulated group, whereas sham-operated and control rats showed similar AP between the first and second recording periods. Heart rate variability (HRV) evaluated using time and frequency domain tools and a nonlinear approach (symbolic analysis) suggested that hypertensive rats with electrodes around the CS, stimulated or not, exhibited a shift in cardiac sympathovagal balance towards parasympathetic tone. The relaxation response to acetylcholine in endothelium-intact mesenteric arteries was enhanced in rats that underwent CS stimulation for 48 h. In conclusion, long-term CS stimulation is effective in reducing AP levels, improving HRV and increasing mesenteric vascular relaxation in L-NAME hypertensive rats. Moreover, only the presence of electrodes around the CS is effective in eliciting changes in HRV similar to those observed in stimulated rats.

Effect of chronic stress on cardiovascular and ventilatory responses activated by both chemoreflex and baroreflex in rats.

Chronic stress results in physiological and somatic changes. It has been recognized as a risk factor for several types of cardiovascular dysfunction and changes in autonomic mechanisms, such as baroreflex and chemoreflex activity. However, the effects of different types of chronic stress on these mechanisms are still poorly understood. Therefore, in the present study, we investigated, in adult male rats, the effect of repeated restraint stress (RRS) or chronic variable stress (CVS) on baroreflex, chemoreflex and heart rate variability in a protocol of 14 days of stress sessions. Exposure to RRS and CVS indicated no changes in the basal level of either arterial pressure or heart rate. However, RRS and CVS were able to attenuate sympathovagal modulation and spontaneous baroreflex gain. Additionally, only RRS was able to increase the power of the low-frequency band of the systolic blood pressure spectrum, as well as the slope of linear regression of baroreflex bradycardic and tachycardic responses induced by vasoactive compounds. Additionally, our study is one of the first to show that exposure to RRS and CVS decreases the magnitude of the pressor response and potentiates respiratory responses to chemoreflex activation, which can trigger cardiovascular and respiratory pathologies. Furthermore, the basal respiratory parameters, such as minute ventilation and tidal volume, were significantly decreased by both protocols of chronic stress. However, only CVS increased the basal respiratory frequency. In this way, the findings of the present study demonstrate the impact of chronic stress in terms of not only depressive-like behavior but also alterations of the autonomic baroreflex responses and cardiocirculatory variability (systolic blood pressure and pulse interval).Our results provide evidence that chronic stress promotes autonomic dysregulation, and impairment of baroreflex, chemoreflex and heart rate variability.

Time Course of Hemodynamic Responses to Different Doses of Lipopolysaccharide in Unanesthetized Male Rats.

Lipopolysaccharide (LPS) administration is a well-known method to induce systemic inflammation widely used for investigating new therapeutic strategies for sepsis treatment, which is characterized by clinical manifestations such as tachycardia and hypotension. However, there are different doses of LPS used in several studies, and the hemodynamic responses were not always well characterized. Thus, the present study aimed to evaluate the arterial pressure, heart rate, heart rate variability, and baroreflex function from rats, over time, to different doses of LPS. Femoral artery and vein catheters were inserted into anesthetized Wistar-Hannover male rats for arterial pressure recording and LPS administration, respectively. On the next day, the arterial pressure was recorded before and after (90, 180, and 360 min) LPS injection (0.06, 20, 30, and 40 mg/kg). All doses of LPS tested increased the heart rate and decreased baroreflex sensitivity over time. In addition, while LPS administration of 20, 30, and 40 mg/kg increased the mean arterial pressure over time, 0.06 mg/kg decreased the mean arterial pressure at 360 min, as compared to baseline values. Furthermore, high doses of LPS decreased the power of the HF band of the cardiac interval spectrum over time, and the higher dose increased the power of the LF band. Our data indicate that high doses of LPS promote hypertensive response over time, while a low dose decreases arterial pressure. Moreover, the changes in heart rate variability and baroreflex function elicited by LPS may be not associated with arterial pressure response produced by the endotoxemia.

Revisiting the Sequence Method for Baroreflex Analysis.

The sequence method is an important approach to assess the baroreflex function, mainly because it is based on the spontaneous fluctuations of beat-by-beat arterial pressure (for example, systolic arterial pressure or SAP) and pulse interval (PI). However, some studies revealed that the baroreflex effectiveness index (BEI), calculated through the sequence method, shows an intriguing oscillatory pattern as function of the delay between SAP and PI. It has been hypothesized that this pattern is related to the respiratory influence on SAP and/or PI variability, limiting the SAP ramps to 3 or 4 beats of length. In this study, this hypothesis was tested by assessing the sequence method using raw (original) and filtered series. Results were contrasted to the well-established transfer function, estimated between SAP and PI. Continuous arterial pressure recordings were obtained from healthy rats (N = 61) and beat-by-beat series of SAP and PI were generated. Low-pass (LP) and high-pass (HP) filtered series of SAP and PI were created by filtering the original series with a cutoff frequency of 0.8 Hz. Original series were analyzed by either the sequence method or cross-spectral analysis (transfer function) at low- (LF) and high- (HF) frequency bands, while filtered series were evaluated only by the sequence method. Baroreflex sensitivity (BRS) and BEI of original series, calculated by sequence method, was highly (85-90%) determined by HP series, with no significant association between original and LP series. A high correlation (>0.7) was found between the BRS estimated from original series (sequence method) and HF band (transfer function), as well as for LP series (sequence method) and LF band (transfer function). These findings confirmed the hypothesis that the sequence method quantifies only the high-frequency components of the baroreflex, neglecting the low-frequency influences, such as the Mayer waves. Therefore, we propose using both the original and LP filtered time series for a broader assessment of the baroreflex function using the sequence method.

Use of behavioural and physiological responses for scoring sound sensitivity in dogs.

Sound sensitive dogs have exaggerated responses to sound stimuli that can negatively impact the welfare of the dog. Behavioural reactions combined with the response to sound involve a marked autonomic imbalance towards sympathetic predominance and release of cortisol. The purpose of the present study was to evaluate, in the laboratory, the cardiac autonomic modulation using heart rate variability (HRV) analysis, serum cortisol levels and behavioural parameters in response to sounds of fireworks in dogs with a history of sensitivity to fireworks. Based on these data, and combining qualitative measures and categorical measures, we propose one short and one full index of sound sensitivity in dogs. Six privately owned dogs with no history and another twelve dogs with a history of sound sensitivity to fireworks were used. The sound stimulus consisted of a standardised recording of fireworks (180-seconds long) with a peak intensity of 103-104 dB. The cardiac intervals were recorded using a frequency meter (Polar® RS800CX model) to evaluate the HRV, and the acquired data were processed using CardioSeries 2.4.1 software. Twenty-one behavioural parameters were analysed quantitatively by time, frequency or categorically by scores and were grouped in behavioural categories of arousal, fear, relaxation and "other". Sound sensitive dogs had exacerbated autonomic responses to the sound stimulus in the laboratory compared to non-sensitive dogs, with higher LF/HF ratios suggesting autonomic imbalance towards sympathetic predominance, but the cortisol levels were similar between the sensitive and non-sensitive dogs. Sound sensitive dogs showed pronounced responses for the parameters: alert and attention, search sound, startle, trembling, hiding, run away and less intense responses for the parameters rest and wink/sleep. Furthermore, the behavioural categories of arousal, fear, relaxation (lack of) and LF/HF were correlated to the caregiver's perception of the sound sensitivity of the dogs. Not only the short index for sound sensitivity (behavioural categories arousal, fear and relaxation, and LF/HF ratio) but also the full index for sound sensitivity (all behavioural categories, LF/HF and cortisol levels) was highly correlated to sound fear response at home. These indexes can contribute to the development of strategies to treat sound sensitive dogs.

Effects of acupuncture on the heart rate variability, cortisol levels and behavioural response induced by thunder sound in beagles.

Sound stimuli such as fireworks, firearms, and claps of thunder have been used as a stress reactivity model for dogs. Acupuncture has been widely used to treat and prevent physiological and behavioural disorders induced by stress. Our study aims to evaluate the effects of acupuncture on cardiac autonomic modulation (heart rate variability - HRV), behavioural (reactivity) and endocrine (cortisol levels) responses in dogs exposed to sounds of thunder. Twenty-four laboratory beagles (12 males and 12 females, 1-6years old) with no history of phobia to thunder were subjected to a sound stimulus that consisted of a standardized recording of thunder over a 150s period with a maximum intensity of 103-104dB. Before the sound, the dogs underwent a 20-minute session of needle insertion at acupuncture points Yintang, GV20, HT7, PC6 and ST36 (ACUP), in non-points (NP) or left undisturbed (CTL). Cardiac intervals were recorded using a frequency meter (RS 800cx, Polar, Kempele, Finland) to evaluate the HRV, and the data were later analysed using CardioSeries v2.4.1 software. Acupuncture (ACUP) changed the sympathovagal balance with a shift towards parasympathetic modulation, reducing the prompt sound-induced increase in LF/HF (low frequency/high frequency) ratio and in the power of the LF band of the cardiac interval spectrum, and decreased the power of the HF band of the cardiac interval spectrum (p<0.05); however there was no change in the heart rate. Acupuncture reduced the behavioural response induced by sounds of thunder (when all behavioural parameters were considered together) and the behaviours hiding, restlessness, bolting and running around (when the parameters were analysed separately (p<0.05). There were no changes in cortisol levels due to the sound stimulus or acupuncture. Our results demonstrate that a session of acupuncture prior to sound stimulus can reduce cardiac autonomic and behavioural responses, without changing cortisol levels in beagles.

Modulation of experimental arthritis by vagal sensory and central brain stimulation.

Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera. Here, we report that vagal stimulation modulates arthritic joint inflammation through a novel "afferent" pathway mediated by the locus coeruleus (LC) of the central nervous system. Afferent vagal stimulation activates two sympatho-excitatory brain areas: the paraventricular hypothalamic nucleus (PVN) and the LC. The integrity of the LC, but not that of the PVN, is critical for vagal control of arthritic joint inflammation. Afferent vagal stimulation suppresses articular inflammation in the ipsilateral, but not in the contralateral knee to the hemispheric LC lesion. Central stimulation is followed by subsequent activation of joint sympathetic nerve terminals inducing articular norepinephrine release. Selective adrenergic beta-blockers prevent the effects of articular norepinephrine and thereby abrogate vagal control of arthritic joint inflammation. These results reveals a novel neuro-immune brain map with afferent vagal signals controlling side-specific articular inflammation through specific inflammatory-processing brain centers and joint sympathetic innervations.

Increased Expression of Macrophage Migration Inhibitory Factor in the Nucleus of the Solitary Tract Attenuates Renovascular Hypertension in Rats.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is an intracellular inhibitory regulator of the actions of angiotensin II in the central nervous system. Renovascular hypertensive 2-kidney, 1-clip (2K1C) rats have an increased activity of the renin-angiotensin system and a decrease in baroreflex function compared to normotensive (NT) rats. In the present study, we tested the effects of MIF overexpression within the nucleus of the solitary tract (NTS), a key brainstem region for cardiovascular regulation, on the development of hypertension, on baroreflex function, and on water and food intake in 2K1C rats. METHODS: Holtzman NT rats received a silver clip around the left renal artery to induce 2K1C hypertension. Three weeks later, rats were microinjected in the NTS with AAV2-CBA-MIF, to increase the expression of MIF, or with the control vector AAV2-CBA-enhanced green fluorescent protein. Mean arterial pressure (MAP) and heart rate were recorded by telemetry. Baroreflex function was tested, and water and food intake were also measured. RESULTS: Increasing MIF expression in the NTS of 2K1C rats attenuated the development of hypertension, reversed the impairment of baroreflex function, and reduced the increase in water intake. In contrast to 2K1C rats, similar increases in MIF expression in the NTS of NT rats produced no changes in baseline MAP, baroreflex function, or water intake. CONCLUSIONS: These results indicate that an increased expression of MIF within the NTS attenuates the development of hypertension and restores the baroreflex function in 2K1C rats.

Autonomic, endocrine and behavioural responses to thunder in laboratory and companion dogs.

Dogs are highly sensitive to sound stimuli, especially fireworks, firearms, and thunder, and therefore these sounds are used as models of stress reactivity in dogs. Companion and laboratory dogs may respond differently to stressful stimuli, due to differences in management and their relationship with humans. Therefore, the reactivity of beagle dogs (laboratory) and companion dogs to an acute acoustic stress model was studied by analysing the heart rate variability (HRV; cardiac interval values), serum cortisol levels and various behavioural parameters. Eight beagles and six privately owned dogs with no history of phobia to thunder were used. The sound stimulus consisted of a standardized recording of thunder for 2.5min with a maximum intensity of 103-104dB. To evaluate the HRV, cardiac intervals were recorded using a frequency meter (Polar RS800CX model), and later the data were analysed using CardioSeries 2.4.1 software. In both laboratory and companion dogs, thunder promoted an increase in the power of the LF band of the cardiac interval spectrum, in the LF/HF ratio and in the HR, and a decrease in the power of the HF band of the cardiac interval spectrum. Companion dogs showed higher cortisol levels, than beagles, independently of the time point studied and a significant increase in the cortisol levels 15min after acoustic stress, while beagles did not show any alterations in their cortisol levels in response to the sound. On the other hand, beagles showed higher scores in the trembling, hiding, vigilance, running, salivation, bolting and startle parameters than companion dogs. Our results showed that independently of the sound stimulus, companion dogs had higher cortisol levels than laboratory dogs. Furthermore, the sound stimulus induced a marked autonomic imbalance towards sympathetic predominance in both laboratory and companion dogs. However a significant increase in the cortisol was observed only in companion dogs. On the other hand, in general the behavioural response was more pronounced in laboratory dogs than in companion dogs.

Effects of transcutaneous electrical diaphragmatic stimulation on the cardiac autonomic balance in healthy individuals: a randomized clinical trial / Efeitos da estimulação diafragmática elétrica transcutânea sobre o balanço autonômico cardíaco de indivíduos hígidos: ensaio clínico randomizado / Los efectos de la estimulación eléctrica transcutánea del diafragma en el balance autónomo cardiaco en individuos sanos: estudio clínico aleatorio

ABSTRACT The transcutaneous electrical diaphragmatic stimulation (TEDS) is a technique of respiratory muscle activation that affects breathing pattern and rhythm. In an attempt to evaluate changes in cardiac autonomic balance in response to TEDS in healthy individuals, we used a well-established TEDS model. Twenty-two volunteers aged between 22 and 35 years old, with no cardiac pathology history, were randomized into two groups (control, n = 8; TEDS, n = 14). The individuals were allowed to rest in supine position and were then subjected to the electrical stimulation protocol. The control group was subjected to electrical stimulation at perceptive level, whereas for the TEDS group the electric stimulus generated diaphragm contraction. Cardiac intervals (CI) were sampled by a Polar RS800CX monitor. Cardiac interval variability was studied in the time and frequency domains. In the control group, electrical stimulation did not change cardiac interval length and variability (CI: 761±44 vs. 807±39 ms; RMSSD: 37±9 vs. 42±13 ms ; LF: 69±6 vs. 67±5 nu; HF: 31±6 vs. 33±5 nu; all comparisons versus baseline). Nevertheless, as compared to baseline, TEDS group showed decreased sympathetic cardiac modulation (LF: 43±3 vs. 63±4 nu) and increased parasympathetic cardiac modulation (RMSSD: 109±10 vs. 41±6 ms; HF: 57±3 vs. 37±4 nu) during diaphragmatic stimulation. However, cardiac interval length was not changed by electrical stimulation (CI: 686±59 vs. 780±31 ms). It can be suggested that the use of TEDS stimulus leads to pronounced changes in the cardiac sympathovagal balance, with higher parasympathetic cardiac modulation, possibly induced by increased diaphragmatic excursion.

RESUMO A estimulação diafragmática elétrica transcutânea (EDET) é uma técnica de mobilização da musculatura respiratória que interfere no padrão e no ritmo respiratório. Na tentativa de avaliar as alterações no balanço autonômico cardíaco à EDET em indivíduos saudáveis, foi utilizado um modelo já estabelecido de eletroestimulação diafragmática. 22 voluntários com idades entre 22 e 35 anos, sem histórico cardíaco, foram randomizados em dois grupos (controle, n=8; EDET, n=14). O protocolo de eletroestimulação foi aplicado nos indivíduos em repouso (posição supina). O grupo controle foi submetido a estimulação elétrica em nível perceptivo, enquanto no grupo EDET o estímulo gerava contração diafragmática. Os intervalos cardíacos (CI) foram registrados por cardiofrequencímetro Polar (RS800CX). A variabilidade do intervalo cardíaco foi estudada nos domínios de tempo e frequência. No grupo controle, a estimulação elétrica não alterou a duração do intervalo cardíaco e sua variabilidade (CI: 761±44 vs. 807±39ms; RMSSD: 37±9 vs. 42±13ms; LF: 69±6 vs. 67±5nu; HF: 31±6 vs. 33±5nu), em comparação às condições basais). No entanto, o grupo EDET apresentou diminuição na modulação simpática cardíaca (LF: 43 ±3 vs. 63±4nu) e aumento da modulação parassimpática cardíaca (RMSSD: 109±10 vs. 41±6ms; HF: 57±3 vs. 37±4nu) durante a eletroestimulação diafragmática. No entanto, a duração do intervalo cardíaco não foi alterada por estimulação elétrica (CI: 686±59 vs. 780±31ms). Pode-se sugerir que o uso da EDET promove mudanças acentuadas no balanço simpatovagal, resultando em maior modulação parassimpática cardíaca, possivelmente induzida pelo aumento da mobilidade diafragmática.

RESUMEN La estimulación eléctrica transcutánea del diafragma (EETD) es un método que moviliza la musculatura respiratoria que interfiere en el patrón y en la frecuencia respiratoria. Para evaluar las alteraciones en el balance autónomo cardiaco por la EETD en individuos sanos, se empleó un modelo prestablecido de estimulación eléctrica muscular del diagrama. Han participado 22 voluntarios con edad entre 22 y 35 años, sin enfermedades cardiacas, puestos en grupos aleatorios: Grupo control (n=8) y EETD (n=14). Se aplicó el protocolo de estimulación eléctrica en individuos en posición decúbito supino. Al grupo control se lo sometió a la estimulación eléctrica a nivel perceptual, mientras que en el EETD la estimulación le generaba contracción del diafragma. Los intervalos cardiacos (CI) se registraron a través del monitor de ritmo cardiaco polar (RS800CX). Se estudió la variabilidad del intervalo cardiaco en los dominios tiempo y frecuencia. En el grupo control, la estimulación eléctrica no presentó alteraciones en la duración del intervalo cardiaco y su variabilidad (CI: 761±44 vs. 807±39ms; RMSSD: 37±9 vs. 42±13ms; LF: 69±6 vs. 67±5nu; HF: 31±6 vs. 33±5nu; comparado con las condiciones de base). Pero si comparado las condiciones de base en el grupo EETD presentó una disminución en la modulación simpática cardiaca (LF: 43±3 vs. 63±4nu) y un aumento en la modulación parasimpática cardiaca (RMSSD: 109±10 vs. 41±6ms; HF: 57±3 vs. 37±4nu) durante la realización de este método. Sin embargo, la duración del intervalo cardiaco no presentó alteraciones por la estimulación eléctrica del diafragma (CI: 686±59 vs. 780±31ms). Se puede concluir que el empleo de la EETD promueve cambios significativos en el balance simpático, resultando en una modulación parasimpática cardiaca más grande, posiblemente inducida del aumento de la movilidad del diafragma.

Heart rate variability measure in breast cancer patients and survivors: A systematic review.

PURPOSE: In the current study, we aimed to review literature findings showing the clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in breast cancer (BC) patients and survivors. METHODS: We conducted a systematic review according to The PRISMA Statement in Medline, Scopus and Web of Science (_-2015) databases. The search was limited to articles in English language, published in peer-reviewed journals, and with adult age samples only (e.g., women, patients, or survivors, diagnosed with BC in any stage). We included observational studies and randomized trials. Detailed heart rate variability analysis (instruments, data collection protocol, and analysis methods) was required. Search terms included autonomic nervous system, heart rate variability, sympathetic and parasympathetic nervous system, autonomic dysfunction, vagal nervous and breast neoplasms, breast cancer and breast tumor. RESULTS: Twelve studies were included in this review. The clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in BC patients and survivors is demonstrated by association with effects of BC surgery, and treatments, and the adverse effects of surgery and treatments on survivors (e.g., cardiotoxicity, fatigue, and stress). LIMITATIONS: The strength of evidence of included studies is low: small samples size and heterogeneity, presence of confounders, and observational studies design. CONCLUSIONS: The heart rate variability analysis could be used as a complementary non-invasive tool for the early diagnosis and better prognosis of autonomic dysfunction, and survival in BC patients. There are many potential clinical applications of heart rate variability analysis in BC patients, and the employment of such approaches could lead to lower impairment of autonomic function in this individuals.

Acupuncture Affects Autonomic and Endocrine but Not Behavioural Responses Induced by Startle in Horses.

Startle is a fast response elicited by sudden acoustic, tactile, or visual stimuli in a variety of animals and in humans. As the magnitude of startle response can be modulated by external and internal variables, it can be a useful tool to study reaction to stress. Our study evaluated whether acupuncture can change cardiac autonomic modulation (heart rate variability); and behavioural (reactivity) and endocrine (cortisol levels) parameters in response to startle. Brazilian Sport horses (n = 6) were subjected to a model of startle in which an umbrella was abruptly opened near the horse. Before startle, the horses were subjected to a 20-minute session of acupuncture in acupoints GV1, HT7, GV20, and BL52 (ACUP) and in nonpoints (NP) or left undisturbed (CTL). For analysis of the heart rate variability, ultrashort-term (64 s) heart rate series were interpolated (4 Hz) and divided into 256-point segments and the spectra integrated into low (LF; 0.01-0.07 Hz; index of sympathetic modulation) and high (HF; 0.07-0.50 Hz; index of parasympathetic modulation) frequency bands. Acupuncture (ACUP) changed the sympathovagal balance with a shift towards parasympathetic modulation, reducing the prompt startle-induced increase in LF/HF and reducing cortisol levels 30 min after startle. However, acupuncture elicited no changes in behavioural parameters.

Cardiac autonomic modulation in non-frail, pre-frail and frail elderly women: a pilot study.

Frailty has been defined as a geriatric syndrome that results in high vulnerability to health adverse outcomes. This increased vulnerability state results from dysregulation of multiple physiological systems and its complex interactions. Thus, assessment of physiological systems integrity and of its dynamic interactions seems to be useful in the context of frailty management. Heart rate variability (HRV) analysis provides information about autonomic nervous system (ANS) function, which is responsible to control several physiologic functions. This study investigated the cardiac autonomic modulation by HRV analysis in community-dwelling elderly women classified as non-frail, pre-frail and frail. Twenty-three elderly women were assigned to the following groups: non-frail (n = 8), pre-frail (n = 8) and frail (n = 7). HRV assessment was performed through linear and non-linear analysis of cardiac interval variability. It was observed a higher sympathetic and lower parasympathetic modulation in frail when compared with non-frail and pre-frail groups (p < 0.05) as indicated by frequency domain indices. Additionally, frail group had a decreased 2LV % pattern (that reflects parasympathetic modulation) in the symbolic analysis in comparison with non-frail group. These findings suggest that frail elderly women present an autonomic imbalance characterized by a shift towards sympathetic predominance. Thus, monitoring ANS function in the context of frailty management may be an important strategy to prevention, diagnosis and treatment of this syndrome and its consequences.

Experimental gestational hypothyroidism evokes hypertension in adult offspring rats.

Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to investigate the impact of experimental gestational hypothyroidism (EGH) on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH was induced with methimazole (MMI) 0.02% in drinking water from day 9 of gestation until birth. Sixty day old offspring from MMI-treated dams (OMTD, n=13) or water-treated dams (OWTD, n=13) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased MAP (130.2 ± 2.0 vs 108.8 ± 3.0 mmHg, p<0.001), SAP (157.3 ± 2.9 vs 135.7 ± 4.5mm Hg, p<0.001) and DAP (109.7 ± 1.9 vs 88.4 ± 2.6 mmHg, p<0.001) when compared to OWTD, and had lower HR (355.1 ± 8.9 vs 386.8 ± 9.2 bpm, p<0.05). After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher (7.2 ± 0.8 vs 4.0 ± 0.6 mmHg(2), p<0.01) in OMTD under spontaneous condition. Despite bradycardia, EGH promotes spontaneous hypertension in 60 day old offspring, probably due to increased sympathetic modulation of vessels, which is suggested by the higher LF of SAP. These findings suggest a critical role of maternal THs in the development of fetal cardiovascular and autonomic nervous systems.

Induction of chronic non-inflammatory widespread pain increases cardiac sympathetic modulation in rats.

Fibromyalgia (FM) is characterized by chronic non-inflammatory widespread pain (CWP) and changes in sympathetic function. In attempt to elucidate the pathophysiological mechanisms of FM we used a well-established CWP animal model. We aimed to evaluate changes in cardiac autonomic balance and baroreflex function in response to CWP induction in rats. CWP was induced by two injections of acidic saline (pH 4.0, n=8) five days apart into the left gastrocnemius muscle. Control animals were injected twice with normal saline (pH 7.2, n=6). One day after the second injection of acidic saline or normal saline, the animals had pulse interval (PI) and systolic arterial pressure (SAP) variability, and spontaneous baroreflex sensitivity (BRS) evaluated. After induction of CWP, there was an increase of power in the low frequency (LF) band of PI spectrum (12.75 ± 1.04 nu), a decrease in the high frequency (HF) band (87.25 ± 1.04 nu) and an increase of LF/HF ratio (0.16 ± 0.01), when compared to control animals (7.83 ± 1.13 nu LF; 92.16 ± 1.13 nu HF; 0.08 ± 0.01 LF/HF). In addition, there was an increase of power in the LF band of SAP spectrum (7.93 ± 1.39 mmHg(2)) when compared to control animals (2.97 ± 0.61 mmHg(2)). BRS was lower in acidic saline injected rats (0.59 ± 0.06 ms/mmHg) when compared to control animals (0.71 ± 0.03 ms/mmHg). Our results showed that induction of CWP in rats shifts cardiac sympathovagal balance towards sympathetic predominance and decreases BRS. These data corroborate findings in humans with FM.