Trypanosoma cruzi strains and autonomic nervous system pathology in experimental chagas disease

Lesions involving the sympathetic (para-vertebral ganglia) and para-sympathetic ganglia of intestines (Auerbach plexus) and heart (right atrial ganglia) were comparatively analyzed in mice infected with either of three different strain types of Trypanosoma cruzi, during acute and chronic infection, in an attempt to understand the influence of parasite strain in causing autonomic nervous system pathology. Ganglionar involvement with neuronal destruction appeared related to inflammation, which most of the times extended from neighboring adipose and cardiac, smooth and striated muscular tissues. Intraganglionic parasitism was exceptional. Inflammation involving peripheral nervous tissue exhibited a focal character and its variability in the several groups examined appeared unpredictable. Although lesions were generally more severe with the Y strain, comparative qualitative study did not allow the conclusion, under the present experimental conditions, that one strain was more pathogenic to the autonomic nervous system than others. No special tropism of the parasites from any strain toward autonomic ganglia was disclosed.

Role of mast cell- and non-mast cell-derived inflammatory mediators in immunologic induction of synaptic plasticity

We have previously discovered a long-lasting enhancement of synaptic transmission in mammal autonomic ganglia caused by immunological activation of ganglionic mast cells. Subsequent to mast cell activation, lipid and peptide mediators are released which may modulate synaptic function. In this study we determined whether some mast cell-derived mediators, prostaglandin D2 (PGD2; 1.0 µM), platelet aggregating factor (PAF; 0.3 µM) and U44619 (a thromboxane analogue; 1.0 µM), and also endothelin-1 (ET-1; 0.5 µM) induce synaptic potentiation in the guinea pig superior cervical ganglion (SCG), and compared their effects on synaptic transmission with those induced by a sensitizing antigen, ovalbumin (OVA; 10 µg/ml). The experiments were carried out on SCGs isolated from adult male guinea pigs (200-250 g) actively sensitized to OVA, maintained in oxygenated Locke solution at 37oC. Synaptic potentiation was measured through alterations of the integral of the post-ganglionic compound action potential (CAP). All agents tested caused long-term (LTP; duration ³30 min) or short-term (STP; <30 min) potentiation of synaptic efficacy, as measured by the increase in the integral of the post-ganglionic CAP. The magnitude of mediator-induced potentiation was never the same as the antigen-induced long-term potentiation (A-LTP). The agent that best mimicked the antigen was PGD2, which induced a 75% increase in CAP integral for LTP (antigen: 94%) and a 34% increase for STP (antigen: 91%). PAF-, U44619-, and ET-1-induced increases in CAP integral ranged for LTP from 34 to 47%, and for STP from 0 to 26%. These results suggest that the agents investigated may participate in the induction of A-LTP

Involvement of the autonomic nervous system in Chagas heart disease

The autonomic nervous system and especially the intracardiac autonomic nervous system is involved in Chagas' disease. Ganglionitis and periganglionitis were noted in three groups ofpatients dying with Chagas'disease: 1) Those in heart failure; 2) Those dying a sudden, non violent death and; 3) Those dying as a consequence ofaccidents or homicide. Hearts in the threegroups also revealed myocarditis and scattered involvement of intramyocardial ganglion cells as well as lesions of myelinic and unmyelinic fibers ascribable to Chagas'disease. In mice with experimentally induced Chagas' disease weobserved more intensive neuronal lesions of the cardiac ganglia in the acute phase of infection. Perhaps neuronal loss has a role in the pathogenesis of Chagas cardiomyopathy. However based on our own experience and on other data from the literature we conclude that the loss of neurones is not the main factor responsible for the manifestations exhibited by chronic chagasic patients. On the other hand the neuronal lesions may have played a role in the sudden death ofone group of patients with Chagas'disease but is difficult to explain the group of patients who did not die sudderly but instead progressed to cardiac failure.

BLOOD VESSELS IN GANGLIA IN HUMAN ESOPHAGUS MIGHT EXPLAIN THE HIGHER FREQUENCY OF MEGAESOPHAGUS COMPARED WITH MEGACOLON

This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon.

Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

Is autonomic function associated with left ventricular systolic function in Chagas heart disease patients undergoing treatment for heart failure?

Introduction The association between cardiac autonomic and left ventricular (LV) dysfunction in Chagas disease (ChD) is controversial. Methods A standardized protocol that includes the Valsalva maneuver, a respiratory sinus arrhythmia (RSA) test, and an echocardiographic examination was used. Spearman correlation coefficients (rho) were used to investigate associations. Results The study population consisted of 118 ChD patients undergoing current medical treatment, with an average LV ejection fraction of 51.4±2.6%. The LV ejection fraction and diastolic dimension were correlated with the Valsalva index (rho=0.358, p<0.001 and rho=-0.266, p=0.004, respectively) and the RSA (rho=0.391, p<0.001 and rho=-0.311, p<0.001, respectively). Conclusions The impairment of LV function is directly associated with a reduction of cardiac autonomic modulation in ChD.

Relationship between obsessive-compulsive disorders and diseases affecting primarily the basal ganglia

Obsessive-compulsive disorder (OCD) has been reported in association with some neurological diseases that affect the basal ganglia such as Tourette's syndrome, Sydenham's chorea, Parkinson's disease, and Huntington's disease. Furthermore, studies such as neuroimaging, suggest a role of the basal ganglia in the pathophysiology of OCD. The aim of this paper is to describe the association of OCD and several neurologic disorders affecting the basal ganglia, report the existing evidences of the role of the basal ganglia in the pathophysiology of OCD, and analyze the mechanisms probably involved in this pathophysiology.

Prostate innervation and local anesthesia in prostate procedures

The nerve supply of the human prostate is very abundant, and knowledge of the anatomy contributes to successful administration of local anesthesia. However, the exact anatomy of extrinsic neuronal cell bodies of the autonomic and sensory innervation of the prostate is not clear, except in other animals. Branches of pelvic ganglia composed of pelvic (parasympathetic) and hypogastric (sympathetic) nerves innervate the prostate. The autonomic nervous system plays an important role in the growth, maturation, and secretory function of this gland. Prostate procedures under local anesthesia, such as transurethral prostatic resections or transrectal ultrasound-guided prostatic biopsy, are safe, simple, and effective. Local anesthesia can be feasible for many special conditions including uncomplicated prostate surgery and may be particularly useful for the high-risk group of patients for whom inhalation or spinal anesthesia is inadvisable.

Hormonal and cardiovascular reflex assessment in a female patient with pure autonomic failure

We report the case of a 72-year-old female with pure autonomic failure, a rare entity, whose diagnosis of autonomic dysfunction was determined with a series of complementary tests. For approximately 2 years, the patient has been experiencing dizziness and a tendency to fall, a significant weight loss, generalized weakness, dysphagia, intestinal constipation, blurred vision, dry mouth, and changes in her voice. She underwent clinical assessment and laboratory tests (biochemical tests, chest X-ray, digestive endoscopy, colonoscopy, chest computed tomography, abdomen and pelvis computed tomography, abdominal ultrasound, and ambulatory blood pressure monitoring). Measurements of catecholamine and plasmatic renin activity were performed at rest and after physical exercise. Finally the patient underwent physiological and pharmacological autonomic tests that better diagnosed dysautonomia.

Autonomic Modulation of the Heart in Systemic Arterial Hypertension

OBJECTIVE: To analyze the heart rate variability in patients with mild to moderate systemic arterial hypertension. METHODS: Thirty-two healthy (group I) and 70 systemic arterial hypertensive (group II) individuals, divided according to age (40 to 59 and 60 to 80 years old, respectively) and with a similar distribution by sex were studied. Thirty-one had left ventricular hypertrophy (LVH), 22 were overweight, and 16 had Type II diabetes mellitus. Smoking, alcohol ingestion, and sedentary habits were the same between groups. Variability in heart rate was analyzed in the time domain, using standard deviations of normal RR intervals (SDNN) and the differences between maximal brady- and tachycardia (D-BTmax) during sustained inspiration. Analysis of the frequency band of the power spectrum between 0.05 and 0.40 Hz at rest and during controlled respiration was chosen for analysis of the frequency domain. RESULTS: In both time and frequency domains, variables were lower in group II than in group I. Within groups, statistically significant variables were only found for individuals in the 40 to 59 year old group. The presence of LVH, overweight, or diabetes mellitus did not influence the variability in heart rate to a significant extent. CONCLUSION: Variability in heart rate was a valuable instrument for analyzing autonomic modulation of the heart in arterial hypertension. The autonomic system undergoes significant losses in cardio-modulatory capacity, more evident in subjects between 40 and 59 years old. In those over 60 years old, reduced variability in heart rate imposed by aging was not significantly influenced by the presence of systemic arterial hypertension.

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

Background: Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective: To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods: Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results: The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion: Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

Assessment of Autonomic Function by Phase Rectification of RRInterval Histogram Analysis in Chagas Disease

Background:In chronic Chagas disease (ChD), impairment of cardiac autonomic function bears prognostic implications. Phase‑rectification of RR-interval series isolates the sympathetic, acceleration phase (AC) and parasympathetic, deceleration phase (DC) influences on cardiac autonomic modulation.Objective:This study investigated heart rate variability (HRV) as a function of RR-interval to assess autonomic function in healthy and ChD subjects.Methods:Control (n = 20) and ChD (n = 20) groups were studied. All underwent 60-min head-up tilt table test under ECG recording. Histogram of RR-interval series was calculated, with 100 ms class, ranging from 600–1100 ms. In each class, mean RR-intervals (MNN) and root-mean-squared difference (RMSNN) of consecutive normal RR-intervals that suited a particular class were calculated. Average of all RMSNN values in each class was analyzed as function of MNN, in the whole series (RMSNNT), and in AC (RMSNNAC) and DC (RMSNNDC) phases. Slopes of linear regression lines were compared between groups using Student t-test. Correlation coefficients were tested before comparisons. RMSNN was log-transformed. (α < 0.05).Results:Correlation coefficient was significant in all regressions (p < 0.05). In the control group, RMSNNT, RMSNNAC, and RMSNNDCsignificantly increased linearly with MNN (p < 0.05). In ChD, only RMSNNAC showed significant increase as a function of MNN, whereas RMSNNT and RMSNNDC did not.Conclusion:HRV increases in proportion with the RR-interval in healthy subjects. This behavior is lost in ChD, particularly in the DC phase, indicating cardiac vagal incompetence.

Cardiovascular Autonomic Dysfunction in Patients with Morbid Obesity

Abstract Background: Morbid obesity is directly related to deterioration in cardiorespiratory capacity, including changes in cardiovascular autonomic modulation. Objective: This study aimed to assess the cardiovascular autonomic function in morbidly obese individuals. Methods: Cross-sectional study, including two groups of participants: Group I, composed by 50 morbidly obese subjects, and Group II, composed by 30 nonobese subjects. The autonomic function was assessed by heart rate variability in the time domain (standard deviation of all normal RR intervals [SDNN]; standard deviation of the normal R-R intervals [SDNN]; square root of the mean squared differences of successive R-R intervals [RMSSD]; and the percentage of interval differences of successive R-R intervals greater than 50 milliseconds [pNN50] than the adjacent interval), and in the frequency domain (high frequency [HF]; low frequency [LF]: integration of power spectral density function in high frequency and low frequency ranges respectively). Between-group comparisons were performed by the Student’s t-test, with a level of significance of 5%. Results: Obese subjects had lower values of SDNN (40.0 ± 18.0 ms vs. 70.0 ± 27.8 ms; p = 0.0004), RMSSD (23.7 ± 13.0 ms vs. 40.3 ± 22.4 ms; p = 0.0030), pNN50 (14.8 ± 10.4 % vs. 25.9 ± 7.2%; p = 0.0061) and HF (30.0 ± 17.5 Hz vs. 51.7 ± 25.5 Hz; p = 0.0023) than controls. Mean LF/HF ratio was higher in Group I (5.0 ± 2.8 vs. 1.0 ± 0.9; p = 0.0189), indicating changes in the sympathovagal balance. No statistical difference in LF was observed between Group I and Group II (50.1 ± 30.2 Hz vs. 40.9 ± 23.9 Hz; p = 0.9013). Conclusion: morbidly obese individuals have increased sympathetic activity and reduced parasympathetic activity, featuring cardiovascular autonomic dysfunction.