Neuromuscular electrical stimulation but not photobiomodulation therapy improves cardiovascular parameters of rats with heart failure.

The aim of the present study was to analyze the effect of neuromuscular electrical stimulation (NMES) and photobiomodulation (PBMT) on the cardiovascular parameters, hemodynamic function, arterial baroreflex sensitivity (BRS), and autonomic balance (ANS) of rats with heart failure (HF). Male Wistar rats (220-290 g) were organized into five groups: Sham (n = 6), Control-HF (n = 5), NMES-HF (n = 6), PBMT-HF (n = 6), and NMES + PBMT-HF (n = 6). Myocardial infarction (MI) was induced by left coronary artery ligation. Animals were subjected to an eight-week NMES and PBMT protocol. Statistical analysis included the General Linear Model (GLM) followed by a Bonferroni post-hoc test. Rats of the NMES-HF group showed a higher MI area than the Control-HF (P = 0.003), PBMT-HF (P = 0.002), and NMES + PBMT-HF (P = 0.012) groups. NMES-HF and NMES + PBMT-HF showed higher pulmonary congestion (P = 0.004 and P = 0.02) and lower systolic pressure (P = 0.019 and P = 0.002) than the Sham group. NMES + PBMT-HF showed lower mean arterial pressure (P = 0.02) than the Sham group. Control-HF showed a higher heart rate than the NMES-HF and NMES + PBMT-HF (P = 0.017 and P = 0.013) groups. There was no difference in the BRS and ANS variables between groups. In conclusion, eight-week NMES isolated or associated with PBMT protocol reduced basal heart rate, systolic and mean arterial pressure, without influence on baroreflex sensibility and autonomic control, and no effect of PBMT was seen in rats with HF.

Castration alters the number and structure of dendritic spines in the male posterodorsal medial amygdala.

The posterodorsal medial amygdala (MePD) is responsive to androgens and participates in the integration of olfactory/vomeronasal stimuli for the display of sexual behavior in rats. Adult gonadectomy (GDX) affects the MePD structural integrity at the same time that impairs male mating behavior. At the cellular level, dendritic spines modulate excitatory synaptic transmission, strength, and plasticity. Here, we describe the effect of GDX on the number and shape of dendritic spines in the right and left MePD using confocal microscopy and 3D image reconstruction. Age-matched adult rats were intact (n = 6), submitted to a sham procedure (n = 4) or castrated and studied 90 days after GDX (n = 5). The MePD neurons have a density of 1.1 spines/dendritic µm composed of thin, mushroom-like, stubby/wide, and few ramified or atypical spines. Irrespective of brain hemisphere, GDX decreased the dendritic spine density in the MePD, but induced different effects on each spine type. That is, compared to control groups, GDX reduced (i) the number (up to 50%) of thin, mushroom-like, and ramified spines, and (ii) the size and the neck length of thin spines as well as the head diameter of ramified spines. Besides, GDX increased the number of stubby/wide and atypical spines (up to 140% and 400%, respectively). These data show that GDX promotes a cellular and synaptic reorganization in a spine-specific manner in the MePD. By altering the number and shape of these connectional elements, GDX can affect the neural transmission and hinder the function of integrated brain circuitries in the male brain.

Functional capacity in a rat model of heart failure: impact of myocardial infarct size.

NEW FINDINGS: What is the central question of this study? To the best of our knowledge, no studies have evaluated oxygen uptake, carbon dioxide production and exercise tolerance in rats that have undergone myocardial infarction classified by myocardial infarct (MI) size. What is the main finding and its importance? Oxygen uptake and exercise intolerance are MI size dependent, and classification based on MI size can distinguish rats with functional capacity impairment. Rats with a large MI (>40% of the left ventricle) might provide a good model for the testing of new therapies that have the potential to modify the variables of functional capacity. Oxygen uptake (V̇O2) and exercise tolerance in rats classified by myocardial infarct (MI) size are underexplored. The aim of this study was to evaluate V̇O2, carbon dioxide production (V̇CO2) and exercise tolerance in rats that had undergone myocardial infarction. Fourteen weeks after myocardial infarction or sham surgery, rats underwent an integrated approach to evaluation of left ventricular function and V̇O2/V̇O2V̇CO2V̇CO2, exercise tolerance and skeletal muscle weight. Based on determination of MI size, rats were assigned to sham-operated controls (Sham, n = 12), small myocardial infarction (SMI, n = 8) and large myocardial infarction (LMI, n = 5) groups. The LMI rats showed lower systolic (ejection fraction and fractional shortening) and diastolic (E/A ratio) left ventricular function compared with SMI. Maximal V̇O2 (∼24%, P < 0.05), V̇O2 reserve (∼30%, P < 0.05), time to exhaustion (∼36%, P < 0.05) and maximal velocity (∼30%, P < 0.05) were lower in LMI compared with sham-operated control animals, with no difference between SMI rats and sham-operated controls. Maximal V̇CO2 and respiratory exchange ratio showed no significant difference between MI rats and sham-operated control rats. The LMI rats demonstrated lower gastrocnemius weight (∼12%, P < 0.05) and soleus weight (∼19%, P = 0.07) compared with sham-operated control rats. Significant correlations between MI size, left ventricular end-diastolic pressure, right ventricle hypertrophy, pulmonary congestion, ejection fraction and fractional shortening with maximal V̇O2 and distance run were observed. Oxygen uptake and exercise intolerance are MI size dependent.

Exercise training attenuates the pressor response evoked by peripheral chemoreflex in rats with heart failure.

The effects of exercise training (ExT) on the pressor response elicited by potassium cyanide (KCN) in the rat model of ischemia-induced heart failure (HF) are unknown. We evaluated the effects of ExT on chemoreflex sensitivity and its interaction with baroreflex in rats with HF. Wistar rats were divided into four groups: trained HF (Tr-HF), sedentary HF (Sed-HF), trained sham (Tr-Sham), and sedentary sham (Sed-Sham). Trained animals underwent to a treadmill running protocol for 8 weeks (60 m/day, 5 days/week, 16 m/min). After ExT, arterial pressure (AP), baroreflex sensitivity (BRS), peripheral chemoreflex (KCN: 100 µg/kg body mass), and cardiac function were evaluated. The results demonstrate that ExT induces an improvement in BRS and attenuates the pressor response to KCN relative to the Sed-HF group (P < 0.05). The improvement in BRS was associated with a reduction in the pressor response following ExT in HF rats (P < 0.05). Moreover, ExT induced a reduction in left ventricular end-diastolic pressure and pulmonary congestion compared with the Sed-HF group (P < 0.05). The pressor response to KCN in the hypotensive state is decreased in sedentary HF rats. These results suggest that ExT improves cardiac function and BRS and attenuates the pressor response evoked by KCN in HF rats.

Glutamate and GABA in the medial amygdala induce selective central sympathetic/parasympathetic cardiovascular responses.

Glutamate and γ-aminobutyric acid (GABA) participate in central cardiovascular control, and are found in the rat posterodorsal medial amygdala (MePD), an area of the forebrain that modulates emotional/social behaviors. Here we tested whether these neurotransmitters in the MePD could change the basal activity, chemoreflex, and baroreflex cardiovascular responses in awake rats. Power spectral analysis and symbolic analysis were used to evaluate these responses. Microinjections of saline, glutamate (2 µg), or GABA (61 ng or 100 µg; n = 5-7 rats per group) did not affect basal parameters or chemoreflex responses. However, baroreflex responses showed marked changes. Glutamate increased power spectral and symbolic sympathetic indexes related to both cardiac and vascular modulations (P < 0.05). In turn, the displacement of the baroreflex half-maximal heart rate (HR) response was associated with a GABA (61 ng) mediated decrease in the upper plateau (P < 0.05). Administration of GABA (61 ng, but not 100 µg) also increased HR variability (P < 0.05), in association with parasympathetic activation. These data add novel evidence that the MePD can promote selective responses in the central regulation of the cardiovascular system, i.e., glutamate in the MePD evoked activation of a central sympathetic reflex adjustment, whereas GABA activated a central parasympathetic one.

Respiratory Muscle Training Improves Chemoreflex Response, Heart Rate Variability, and Respiratory Mechanics in Rats With Heart Failure.

BACKGROUND: The aim of the present report was to evaluate respiratory muscle training (RMT) effects on hemodynamic function, chemoreflex response, heart rate variability, and respiratory mechanics in rats with heart failure (HF rats). METHODS: Wistar rats were divided into 4 groups: sedentary-sham (Sed-Sham, n = 8), respiratory muscle trained-sham (RMT-Sham, n = 8), sedentary-HF (Sed-HF, n = 8) and respiratory muscle trained-HF (RMT-HF, n = 8). Animals were submitted to an RMT protocol performed 30 minutes per day, 5 days per week for 6 weeks, whereas the sedentary animals did not exercise. RESULTS: In HF rats, RMT promoted the reduction of left ventricular end-diastolic pressure, right ventricular hypertrophy, and pulmonary edema. Moreover, RMT produced a reduction in pressure response during chemoreflex activation, sympathetic modulation, and sympathetic vagal balance in addition to an increase in parasympathetic modulation. Also after RMT, HF rats demonstrated a reduction in respiratory system resistance, tissue resistance, Newtonian resistance, respiratory system compliance, and quasistatic compliance. CONCLUSIONS: These findings suggested that 6 weeks of RMT in HF rats promoted beneficial adaptations in hemodynamics, autonomic function, and respiratory mechanics and attenuated pressure response evoked by chemoreflex activation in HF rats.

Effect of prior exercise training and myocardial infarction-induced heart failure on the neuronal and glial densities and the GFAP-immunoreactivity in the posterodorsal medial amygdala of rats.

Exercise training has neuroprotective effects whereas myocardial infarction (MI) and heart failure (HF) can cause neuronal death and reactive gliosis in the whole amygdala. The posterodorsal medial amygdala (MePD) is involved with cardiovascular reflexes and the central control of sympathetic/parasympathetic responses. Our aim was to study the effects of prior exercise training and of MI-induced HF on the neuronal and glial densities and the glial fibrillary acidic protein-immunoreactivity (GFAP-ir) in the MePD of adult male rats. Animals (n= 5/group) were: control, sedentary submitted to a sham MI (Sed Sham), sedentary submitted to MI/HF (Sed HF), trained on a treadmill and submitted to a sham MI (T Sham) or trained on a treadmill and submitted to MI/HF (T HF). The number of neurons and glial cells in the MePD was estimated using the optical fractionator and the GFAP-ir was quantified by optical densitometry. In the respective groups, treadmill training improved physical performance and MI damaged near 40% of the left ventricle. There was a hemispheric lateralization effect on the density of neurons (higher in the right MePD), but no significant difference in either the neuronal or the glial densities due to experimental condition. Regional GFAP-ir results revealed that the Sed HF group had a higher expression in the left MePD compared to the control and the Sed Sham rats (p⟨0.01). The present data did not evidence the effects of training or MI/HF in the MePD cellular density, but indicate a possible local restructuring of astrocytic cytoskeleton after MI/HF in rats.

Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure.

Respiratory muscle training (RMT) improves functional capacity in chronic heart-failure (HF) patients, but the basis for this improvement remains unclear. We evaluate the effects of RMT on the hemodynamic and autonomic function, arterial baroreflex sensitivity (BRS), and respiratory mechanics in rats with HF. Rats were assigned to one of four groups: sedentary sham (n = 8), trained sham (n = 8), sedentary HF (n = 8), or trained HF (n = 8). Trained animals underwent a RMT protocol (30 min/day, 5 day/wk, 6 wk of breathing through a resistor), whereas sedentary animals did not. In HF rats, RMT had significant effects on several parameters. It reduced left ventricular (LV) end-diastolic pressure (P < 0.01), increased LV systolic pressure (P < 0.01), and reduced right ventricular hypertrophy (P < 0.01) and pulmonary (P < 0.001) and hepatic (P < 0.001) congestion. It also decreased resting heart rate (HR; P < 0.05), indicating a decrease in the sympathetic and an increase in the vagal modulation of HR. There was also an increase in baroreflex gain (P < 0.05). The respiratory system resistance was reduced (P < 0.001), which was associated with the reduction in tissue resistance after RMT (P < 0.01). The respiratory system and tissue elastance (Est) were also reduced by RMT (P < 0.01 and P < 0.05, respectively). Additionally, the quasistatic Est was reduced after RMT (P < 0.01). These findings show that a 6-wk RMT protocol in HF rats promotes an improvement in hemodynamic function, sympathetic and vagal heart modulation, arterial BRS, and respiratory mechanics, all of which are benefits associated with improvements in cardiopulmonary interaction.