Effects of chronic cholinergic stimulation associated with aerobic physical training on cardiac morphofunctional and autonomic parameters in spontaneously hypertensive rats.

We investigated hemodynamic, cardiac morphofunctional, and cardiovascular autonomic adaptations in spontaneously hypertensive rats (SHRs) after aerobic physical training associated with chronic cholinergic stimulation. Fifty-four SHRs were divided into two groups: trained and untrained. Each group was further subdivided into three smaller groups: vehicle, treated with pyridostigmine bromide at 5 mg/kg/day, and treated with pyridostigmine bromide at 15 mg/kg/day. The following protocols were assessed: echocardiography, autonomic double pharmacological blockade, heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS). Physical training and pyridostigmine bromide reduced BP and HR and increased vagal participation in cardiac autonomic tonic balance. The associated responses were then potentialized. Treatment with pyridostigmine bromide increased HRV oscillation of both low frequency (LF: 0.2-0.75 Hz) and high frequency (HF: 0.75-3 Hz). However, the association with physical training attenuated HF oscillations. Additionally, treatment with pyridostigmine bromide also increased LF oscillations of BPV. Both treatment groups promoted morphofunctional adaptations, and associated increased ejection volume, ejection fraction, cardiac output, and cardiac index. In conclusion, the association of pyridostigmine bromide and physical training promoted greater benefits in hemodynamic parameters and increased vagal influence on cardiac autonomic tonic balance. Nonetheless, treatment with pyridostigmine bromide alone seems to negatively affect BPV and the association of treatment negatively influences HRV.

Vagal reactivation after a cardiac rehabilitation session associated with hydration in coronary artery disease patients: crossover clinical trial.

This study aimed to investigate the hydration influence on the autonomic responses of coronary artery disease subjects in the immediate recovery period after a cardiovascular rehabilitation session, in view of the risks of a delayed autonomic recovery for this population. 28 males with coronary artery disease were submitted to: (I) Maximum effort test; (II) Control protocol (CP), composed by initial rest, warm-up, exercise and passive recovery; (III) Hydration protocol (HP) similar to CP, but with rehydration during exercise. The recovery was evaluated through the heart rate (HR) variability, HR recovery and by the rate of perceived exertion and recovery. The main results revealed that the vagal reactivation occurred at the first 30 s of recovery in HP and after the first minute in CP. A better behavior of the HR at the first minute of recovery was observed in HP. The rate of perceived exertion had a significant decrease in the first minute of recovery in HP, while in CP this occurred after the third minute. In conclusion, despite an anticipated vagal reactivation found at HP, these results should be analyzed with caution as there were no significant differences between protocols for all variables and the effect sizes were small.

Cigarette smoke exposure causes systemic and autonomic cardiocirculatory changes in rats depending on the daily exposure dose.

AIMS: To evaluate the systemic changes and autonomic cardiocirculatory control of awaken rats chronically exposed to the cigarette smoke (CS) of 1 or 2 cigarettes/day. MAIN METHODS: Rats were exposed to clean air (control) or cigarette smoke of 1 (CS1) or 2 (CS2) cigarettes/animal/day for 30 days. Then, arterial pressure (AP) and heart rate (HR) were recorded in conscious rats to assess spontaneous baroreflex sensitivity and HR and AP variabilities. Evoked baroreflex and cardiac autonomic tone were evaluated by vasoactive drugs and autonomic blockers, respectively. In another group, ventilatory and cardiovascular parameters were recorded under hypoxia and hypercapnia stimulus. At the end of protocols, heart, lung, kidneys and liver were collected for histological analysis. KEY FINDINGS: Rats exposed to CS showed morphological changes, being more evident in the CS2 group. Also, less weight gain and cardiac hypertrophy were prominent in CS2 rats. Basal AP and HR, spontaneous baroreflex sensitivity and cardiovascular variabilities were similar among groups. CS exposure progressively blunted the bradycardia response to phenylephrine (-2.2 ± 0.1 vs. -1.7 ± 0.2 vs. -1.5 ± 0.2) while the tachycardia response to sodium nitroprusside was slightly increased compared to control. Vagal tone was not affected by CS, but CS2 rats exhibited higher sympathetic tone (-25 ± 4 vs. -28 ± 4 vs. -56 ± 9) and lower intrinsic HR (411 ± 4 vs. 420 ± 8 vs. 390 ± 6). Exposure to CS of 2 cigarettes also exacerbated the reflex cardiovascular and ventilatory responses to hypoxia and hypercapnia. SIGNIFICANCE: CS exposure for 30 days promoted systemic changes and autonomic cardiocirculatory dysfunction in rats depending on the daily exposure dose.

Effects of aerobic, resistance and concurrent exercise on pulse wave reflection and autonomic modulation in men with elevated blood pressure.

The acute effects of exercise modes on pulse wave reflection (PWR) and their relationship with autonomic control remain undefined, particularly in individuals with elevated blood pressure (BP). We compared PWR and autonomic modulation after acute aerobic (AE), resistance (RE), and concurrent exercise (CE) in 15 men with stage-1 hypertension (mean ± SE: 34.7 ± 2.5 years, 28.4 ± 0.6 kg/m2, 133 ± 1/82 ± 2 mmHg). Participants underwent AE, RE, and CE on different days in counterbalanced order. Applanation tonometry and heart rate variability assessments were performed before and 30-min postexercise. Aortic pressure decreased after AE (- 2.4 ± 0.7 mmHg; P = 0.01), RE (- 2.2 ± 0.6 mmHg; P = 0.03), and CE (- 3.1 ± 0.5 mmHg; P = 0.003). Augmentation index remained stable after RE, but lowered after AE (- 5.1 ± 1.7%; P = 0.03) and CE (- 7.6 ± 2.4% P = 0.002). Systolic BP reduction occurred after CE (- 5.3 ± 1.9 mmHg). RR-intervals and parasympathetic modulation lowered after all conditions (~ 30-40%; P < 0.05), while the sympathovagal balance increased after RE (1.2 ± 0.3-1.3 ± 0.3 n.u., P < 0.05). Changes in PWR correlated inversely with sympathetic and directly with vagal modulation in CE. In conclusion, AE, RE, and CE lowered central aortic pressure, but only AE and CE reduced PWR. Overall, those reductions related to decreased parasympathetic and increased sympathetic outflows. Autonomic fluctuations seemed to represent more a consequence than a cause of reduced PWR.

Cholinergic-pathway-weakness-associated pancreatic islet dysfunction: a low-protein-diet imprint effect on weaned rat offspring.

Currently, metabolic disorders are one of the major health problems worldwide, which have been shown to be related to perinatal nutritional insults, and the autonomic nervous system and endocrine pancreas are pivotal targets of the malprogramming of metabolic function. We aimed to assess glucose-insulin homeostasis and the involvement of cholinergic responsiveness (vagus nerve activity and insulinotropic muscarinic response) in pancreatic islet capacity to secrete insulin in weaned rat offspring whose mothers were undernourished in the first 2 weeks of the suckling phase. At delivery, dams were fed a low-protein (4% protein, LP group) or a normal-protein diet (20.5% protein, NP group) during the first 2 weeks of the suckling period. Litter size was adjusted to six pups per mother, and rats were weaned at 21 days old. Weaned LP rats presented a lean phenotype (P < 0.01); hypoglycaemia, hypoinsulinaemia and hypoleptinaemia (P < 0.05); and normal corticosteronaemia (P > 0.05). In addition, milk insulin levels in mothers of the LP rats were twofold higher than those of mothers of the NP rats (P < 0.001). Regarding glucose-insulin homeostasis, weaned LP rats were glucose-intolerant (P < 0.01) and displayed impaired pancreatic islet insulinotropic function (P < 0.05). The M3 subtype of the muscarinic acetylcholine receptor (M3mAChR) from weaned LP rats was less responsive, and the superior vagus nerve electrical activity was reduced by 30% (P < 0.01). A low-protein diet in the suckling period malprogrammes the vagus nerve to low tonus and impairs muscarinic response in the pancreatic ß-cells of weaned rats, which are imprinted to secrete inadequate insulin amounts from an early age.

Postnatal intermittent hypoxia enhances phrenic and reduces vagal upper airway motor activities in rats by epigenetic mechanisms.

NEW FINDINGS: What is the central question of this study? What are the alterations in respiratory motor activity that may underlie ventilatory dysfunctions in juvenile and adult animals exposed to postnatal chronic intermittent hypoxia? What is the main finding and its importance? Postnatal chronic intermittent hypoxia modifies the motor activity to pumping and upper airway respiratory muscles in rats, mediated by epigenetic DNA hypermethylation, enhancing resting pulmonary ventilation and predisposing to collapse of the upper airways in juvenile and adult life. ABSTRACT: Periods of apnoea, commonly observed in prematures and newborns, are an important risk factor for the development of cardiorespiratory diseases in adulthood. In the present study, we evaluated changes in pulmonary ventilation and respiratory motor pattern in juvenile and adult rats exposed to postnatal chronic intermittent hypoxia (pCIH). Newborn male Holtzman rats (P1) were submitted to pCIH (6% O2 for 30 s, every 9 min, 8 h a day (09.30-17.30 h)) during their first 10 days of life, while control animals were maintained under normoxic conditions (20.8% O2 ). Thereafter, animals of both groups were maintained under normoxia until the experiments. Unanaesthetized juvenile pCIH rats (n = 27) exhibited elevated tidal volume and respiratory irregularities (P < 0.05) compared to control rats (n = 7). Decerebrate, arterially perfused in situ preparations of juvenile pCIH rats (n = 11) displayed augmented phrenic nerve (PN) burst amplitude and reduced central vagus nerve activity in comparison to controls (n = 10). At adulthood, pCIH rats (n = 5) showed enhanced tidal volume (P < 0.05) and increased respiratory variability compared to the control group (n = 5). The pCIH-induced changes in ventilation and respiratory motor outputs were prevented by treatment with the DNA methyltransferase inhibitor decitabine (1 mg kg-1 , i.p.) during the exposure to pCIH. Our data demonstrate that pCIH in rats impacts, in a persistent way, control of the respiratory pattern, increasing PN activity to the diaphragm and reducing the vagal-related activity to laryngeal muscles, which, respectively, may contribute to improve resting pulmonary ventilation and predispose to collapse of the upper airways during quiet breathing.

Heart rate variability in the tegu lizard, Salvator merianae, its neuroanatomical basis and role in the assessment of recovery from experimental manipulation.

Using long-term, remote recordings of heart rate (fH) on fully recovered, undisturbed lizards, we identified several components of heart rate variability (HRV) associated with respiratory sinus arrhythmia (RSA): 1.) A peak in the spectral representation of HRV at the frequency range of ventilation. 2.) These cardiorespiratory interactions were shown to be dependent on the parasympathetic arm of the autonomic nervous system. 3.) Vagal preganglionic neurons are located in discrete groups located in the dorsal motor nucleus of the vagus and also, in a ventro-lateral group, homologous to the nucleus ambiguus of mammals. 4.) Myelinated nerve fibers in the cardiac vagus enabling rapid communication between the central nervous system and the heart. Furthermore, the study of the progressive recovery of fH in tegu following anesthesia and instrumentation revealed that 'resting' levels of mean fH and reestablishment of HRV occurred over different time courses. Accordingly, we suggest that, when an experiment is designed to study a physiological variable reliant on autonomic modulation at its normal, resting level, then postsurgical reestablishment of HRV should be considered as the index of full recovery, rather than mean fH.

Four-second dynamic exercise testing (T4S) for the assessment of cardiac vagal modulation in obese adolescents.

BACKGROUND: Reduced vagal activity is often present in obese adolescents. Simple and practical strategies for the assessment of isolate parasympathetic outflow in this population are therefore useful. OBJECTIVES: To compare the methods derived from heart rate variability (HRV) analysis at rest and 4 s exercise testing (T4S) for the assessment of cardiac parasympathetic modulation in adolescents classified as obese (OB) or with normal weight (NW). Additionally, associations between total and trunk fat versus autonomic modulation determined by the two methods were calculated. APPROACH: A cross-sectional study was conducted with 50 adolescents (26 OB and 24 NW, 14.7 ± 1.5 years), comparing autonomic indices provided by HRV and T4S. Body fractioning was determined employing dual-energy x-ray absorptiometry (DXA). MAIN RESULTS: The cardiac vagal index (CVI) obtained from T4S and standard time- and frequency-domain HRV measures were lower in OB versus NW (P ⩽ 0.05). Correlations between CVI and HRV indices of cardiac vagal modulation were as follows: CVI versus RMSSD (r = 0.44; P = 0.003); CVI versus pNN50 (r = 0.32; P = 0.04); CVI versus HF (r = 0.35; P = 0.02). Associations between body fat, android/gynoid ratio, and percent trunk fat versus CVI were of similar magnitude and direction than versus HRV indices. SIGNIFICANCE: The T4S proved to be adequate to detect cardiac parasympathetic impairment in obese adolescents. Moreover, vagal modulation assessed by HRV and T4S inversely correlated with visceral adipose tissue. These findings along with the simplicity and safety of the T4S should encourage its use in the assessment of cardiac parasympathetic modulation in obese pediatric populations.

Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease.

PURPOSE: Cardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation. METHODS: Short-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls. RESULTS: Beat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls. CONCLUSIONS: Increased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD.

Symbolic analysis of heart rate fluctuations identifies cardiac autonomic modifications during LPS-induced endotoxemia.

The present study aimed to compare linear and symbolic dynamics (SD) indices for detecting the autonomic cardiac changes produced by endotoxemia in freely-moving rats. In this context, we analyzed ECG-derived R-R time series in freely moving Dark Agouti rats, which received lipopolysaccharide (LPS, n = 9), or vehicle (V, n = 7). Five minutes R-R time series were assessed every hour up to +12 h and + 24 h post-LPS injection. We found that SD indices showed significant differences at +7 h between V vs. LPS groups and at +9 h between basal levels of LPS (-3 h) and post-LPS injection (pre-LPS vs. post-LPS). In general, SD seems more appropriate than linear indices to evaluate the autonomic changes of endotoxemic rats. Overall, the symbolic parameters detected decreased R-R variability and complexity, which indicate a modification of the autonomic regulation during LPS-induced endotoxemia. This modification is probably related to a reduced activity of the cholinergic anti-inflammatory pathway at the long term.

Mechanical somatosensory stimulation decreases blood pressure in patients with Parkinson's disease.

OBJECTIVE: The current study aimed to assess the effects of five cycles of automated mechanical somatosensory stimulation (AMSS) of the fore-feet on blood pressure (BP) and cardiovascular autonomic control in Parkinson's Disease patients. METHODS: Out of 23 patients, 16 underwent an AMSS session every 72 h, for a total of five sessions per patient. Electrocardiogram, noninvasive beat-to-beat blood pressure and respiratory activity were recorded for 20 min in supine position at baseline and after the AMSS sessions. Main outcomes were the changes in SBP and DBP, in the spectral indices of cardiac sympathetic (LFRRn.u.) and vagal (HFRR) modulatory activities, cardiac sympathovagal relationship (LF/HF), vascular sympathetic modulation (LFSAP) and arterial baroreflex sensitivity (sequence technique). Symbolic analysis of heart rate variability provided additional indices of cardiac sympathetic (0V%) and vagal (2UV%) modulation to the sinoatrial node. RESULTS: After five AMSS trials a reduction in SBP (baseline: 131.2 ±â€Š15.5 mmHg; post-AMSS: 122.4 ±â€Š16.2 mmHg; P = 0.0004) and DBP (baseline: 73.2 ±â€Š6.1 mmHg; post-AMSS: 68.9 ±â€Š6.2 mmHg; P = 0.008) was observed. Post-AMSS, spectral and symbolic indices of cardiovascular sympathetic control decreased and arterial baroreflex sensitivity increased (baseline: 5.7 ±â€Š1.3 ms/mmHg; post-AMSS: 11.27 ±â€Š2.7 ms/mmHg). CONCLUSION: AMSS sessions were effective in reducing BP, increasing baroreflex sensitivity and decreasing cardiovascular sympathetic modulation in Parkinson's disease patients. AMSS might be useful to control supine hypertension in Parkinson's disease.

Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

STUDY OBJECTIVES: Current evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects. METHODS: Twenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures. RESULTS: Baseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose. CONCLUSIONS: These findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present.

ACE gene dosage determines additional autonomic dysfunction and increases renal angiotensin II levels in diabetic mice.

OBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II.

Patients with Impaired Descending Nociceptive Inhibitory System Present Altered Cardiac Vagal Control at Rest.

BACKGROUND: Patients with chronic musculoskeletal pain have a higher chance of presenting impairment in cardiovascular autonomic modulation, which may have implications for cardiovascular events. The autonomic nervous system plays an important role in pain modulation. However, it is unclear whether patients with inefficient descending nociceptive inhibition have poorer cardiovascular autonomic modulation. OBJECTIVE: To compare the cardiovascular autonomic modulation of patients with musculoskeletal pain who had normal versus impaired functioning of descending nociceptive inhibitory system (DNIS). STUDY DESIGN: A cross-sectional study. SETTING: Physiotherapy outpatient service. METHODS: Fifty-six patients with musculoskeletal pain were included. Conditioned pain modulation was assessed by the difference of algometric values held in the dorsal forearm and tibialis anterior muscle, before and after a thermal pain stimulus was employed via the cold pressure test (CPT). Patients with inefficient DNIS in both sites were classified as impaired responders (n = 14). The others were classified as normal responders (n = 42). Cardiac autonomic modulation was monitored at rest by heart rate variability (HRV). The blood pressure response to the CPT was used as a proxy of sympathetic responsiveness. RESULTS: Most of the patients were women (60%) and had chronic pain (75%). The groups had similar demographic characteristics. Patients with impaired DNIS showed lower HRV [RMSSD (P = 0.020), SDRR (P = 0.009), HF (ms2) (P = 0.027), LF (ms2) (P = 0.004), and total power (P = 0.002)]. The blood pressure response to CPT was similar between groups (systolic pressure, P = 0.813; diastolic pressure, P = 0.709). LIMITATION: Physical activity level, emotional changes, and visceral pathologies can alter the autonomic nervous system and may represent potential confounders. The low number of patients may have biased the results. CONCLUSION: Patients with impaired DNIS presented lower resting HRV, indicating an altered vagal control of the heart. In contrast, the blood pressure response to a sympathoexcitatory stimulus was preserved.The study was approved by the Research Ethics Committee of Augusto Motta University Centre (CAAE number: 46245215.9.0000.5235), and all patients signed the Informed Consent Form. KEY WORDS: Musculoskeletal pain, autonomic nervous system, heart rate, chronic pain, diffuse noxious inhibitory control, blood pressure, sympathetic nervous system, parasympathetic nervous system.

Cardiac autonomic modulation impairments in advanced breast cancer patients.

AIM: To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. METHODS AND RESULTS: This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. CONCLUSIONS: Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

Vagal stimulation mimics preconditioning and postconditioning of ischemic myocardium in mice by activating different protection mechanisms.

Vagal stimulation (VS) during myocardial ischemia and reperfusion has beneficial effects. However, it is not known whether short-term VS applied before ischemia or at the onset of reperfusion protects the ischemic myocardium. This study was designed to determine whether short-term VS applied before ischemia or at the onset of reperfusion reduces myocardial infarct size (IS), mimicking classic preconditioning and postconditioning. A second objective was to study the participation of muscarinic and nicotinic receptors in the protection of both preischemic and reperfusion stimulation. FVB mice were subjected to 30 min of regional myocardial ischemia followed by 2 h of reperfusion without VS, with 10-min preischemic VS (pVS), or with VS during the first 10 min of reperfusion (rVS). pVS reduced IS, and this effect was abolished by atropine and wortmannin. rVS also reduced IS in a similar manner, and this effect was abolished by the α7-nicotinic acetylcholine receptor blocker methyllycaconitine. pVS increased Akt and glycogen synthase kinase (GSK)-3ß phosphorylation. No changes in Akt and GSK-3ß phosphorylation were observed in rVS. Stimulation-mediated IS protection was abolished with the JAK2 blocker AG490. rVS did not modify IL-6 and IL-10 levels in the plasma or myocardium. Splenic denervation and splenectomy did not abolish the protective effect of rVS. In conclusion, pVS and rVS reduced IS by different mechanisms: pVS activated the Akt/GSK-3ß muscarinic pathway, whereas rVS activated α7-nicotinic acetylcholine receptors and JAK2, independently of the cholinergic anti-inflammatory pathway. NEW & NOTEWORTHY Our data suggest, for the first time, that vagal stimulation applied briefly either before ischemia or at the beginning of reperfusion mimics classic preconditioning and postconditioning and reduces myocardial infarction, activating different mechanisms. We also infer an important role of α7-nicotinic receptors for myocardial protection independent of the cholinergic anti-inflammatory pathway.

Electrophysiology of Cranial Nerve Testing: Cranial Nerves IX and X.

The cranial nerves IX and X emerge from medulla oblongata and have motor, sensory, and parasympathetic functions. Some of these are amenable to neurophysiological assessment. It is often hard to separate the individual contribution of each nerve; in fact, some of the techniques are indeed a composite functional measure of both nerves. The main methods are the evaluation of the swallowing function (combined IX and X), laryngeal electromyogram (predominant motor vagal function), and heart rate variability (predominant parasympathetic vagal function). This review describes, therefore, the techniques that best evaluate the major symptoms presented in IX and X cranial nerve disturbance: dysphagia, dysphonia, and autonomic parasympathetic dysfunction.

ACE gene dosage determines additional autonomic dysfunction and increases renal angiotensin II levels in diabetic mice

OBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II.