Publications by authors named "Valdo José Dias da Silva"

35 Publications

Exercise training ameliorates adrenergic control in spontaneously hypertensive rats.

Clin Exp Hypertens 2021 Feb 14;43(2):101-111. Epub 2020 Sep 14.

Exercise Science, Health and Human Performance Research Group, Department of Sport Sciences, Federal University of Triângulo Mineiro , Uberaba, Brazil.

The goal of this study was to examine vascular control after sympathetic stimulation by tyramine infusion in hypertensive rats submitted to swimming training. To this end, male rats were assigned to the following groups: sedentary (SN) and trained normotensive (TN), sedentary (SH) and trained hypertensive (TH). Arterial pressure (AP), heart rate (HR), HR variability (HRV), AP variability (APV), and cardiac autonomic function were recorded. Following, infusion of tyramine was administrated. The TN and TH showed a lower resting HR compared with their respective sedentary groups ( < .05). Pressure levels were less in TH than SH ( < .05). The TH showed a higher HRV together with a lower APV in comparison to SH ( < .05). The sympathetic modulation of HRV and APV was lower in TH than in SH ( < .05). Both trained groups presented an increased parasympathetic modulation of HRV compared with their respective sedentary groups ( < .05). The TN and TH groups had a higher vagal effect in comparison with their respective sedentary groups ( < .001). The sympathetic effect was lower in TH than in SH ( < .001). Pressor and HR responses to tyramine in different doses were attenuated in TH ( < .001). Further analysis showed a significant association between infusion of tyramine and normalized LF component of HRV (r = 0.84, < .001), systolic APV (r = 0.58, < .001) and diastolic APV (r = 0.49, < .001). In conclusion, exercise training provokes less pressor response variation by tyramine infusion in hypertensive animals suggesting sympathetic nerve endings adjustments and decrease of the vasoconstrictor effect attenuates injury caused by hypertension improving cardiovascular autonomic dysfunction, which can be associated with sympathetic attenuation.
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http://dx.doi.org/10.1080/10641963.2020.1817474DOI Listing
February 2021

T-Cell Immunophenotyping and Cytokine Production Analysis in Patients with Chagas Disease 4 Years after Benznidazole Treatment.

Infect Immun 2019 08 23;87(8). Epub 2019 Jul 23.

Department of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.

The major problem with Chagas disease is evolution of the chronic indeterminate form to a progressive cardiac disease. Treatment diminishes parasitemia but not clinical progression, and the immunological features involved are unclear. Here, we studied the clinical course and the immune response in patients with chronic-phase Chagas disease at 48 months after benznidazole treatment. Progression to the cardiac form of Chagas disease or its aggravation was associated with higher antigen-specific production of interferon gamma (IFN-γ) in patients with cardiac Chagas disease than in patients with the indeterminate form. Predominance of IFN-γ production over interleukin-10 (IL-10) production in antigen-specific cultures was associated with cardiac involvement. Significantly higher numbers of antigen-specific T helper 1 cells (T-Bet IFN-γ) and a significantly higher IFN-γ/IL-10 ratio were observed in patients with cardiac Chagas disease than in patients with the indeterminate form. Cardiac damage was associated with higher numbers of T helper cells than cytotoxic T lymphocytes producing IFN-γ. Patients with cardiac Chagas disease had predominant CD25 and CD25 T regulatory (Treg) subpopulations, whereas patients with the indeterminate form manifested a higher relative mean percentage of CD25 Treg subpopulations. These findings suggest that at 48 months after benznidazole treatment, the disease can worsen or progress to the cardiac form. The progression may be related to increased IFN-γ production (mostly from CD4 T cells) relative to IL-10 production and increased Treg percentages. Patients with the indeterminate form of Chagas disease show a more balanced ratio of proinflammatory and anti-inflammatory cytokines.
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http://dx.doi.org/10.1128/IAI.00103-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652764PMC
August 2019

Effects of diabetes mellitus on myenteric neuronal density and sodium channel expression in the rat ileum.

Brain Res 2019 04 28;1708:1-9. Epub 2018 Nov 28.

Institute of Biological and Natural Science, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil. Electronic address:

Diabetes mellitus (DM) may lead to gastrointestinal motility disorders. Rodent models of DM indicate the presence of morpho-functional abnormalities of the enteric nervous system. Here, we evaluated whether experimental DM can cause changes in the excitatory cholinergic fibers, neuronal density, and voltage-gated sodium channel (Nav) expression in the myenteric plexus of the ileum. After streptozotocin-induced hyperglycemia in female rats progressed for eight weeks, triple immunofluorescence labeling experiments revealed that the neuronal density in DM rats was significantly lower than that in control. On average, the density of total neurons reduced by 52.2% (p = 0.0001), cholinergic neurons by 50.0% (p = 0.0068), and nitrergic neurons by 54.8% (p = 0.0042). The number of neurons per ganglionic area was also significantly reduced (to 28.2% of total neurons, p = 0.0002; 27.7% of cholinergic neurons, p = 0.0002, and 32.1% of nitrergic neurons, p = 0.0016). Furthermore, the density of the cholinergic fibers at the surface of the longitudinal muscle was significantly reduced (DM: 24 ± 3%; p = 0.003, control: 41 ± 2%); however, western-blot analysis did not indicate a reduction in the expression of choline acetyltransferase (ChAT) in the DM group. The Nav1.6 isoform was detected in different myenteric neurons of the ileum. RT-qPCR data did not suggest an alteration of transcripts for ChAT, neuronal nitric oxide synthase, Nav1.3, Nav1.6, or Nav1.7. Our data support the view that chronic DM leads to a reduction of excitatory cholinergic fibers and neuronal density. However, changes in sodium channel expression pattern, which could cause neuronal dysfunction, were not detected.
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http://dx.doi.org/10.1016/j.brainres.2018.11.041DOI Listing
April 2019

Cardiac autonomic modulation and long-term use of amiodarone in patients with chronic Chagasic cardiopathy.

Pacing Clin Electrophysiol 2018 07 8;41(7):788-798. Epub 2018 Jun 8.

Division of Infectious Diseases, Internal Medicine Department, Triangulo Mineiro Federal University, Uberaba, MG, Brazil.

Background: Patients with chronic Chagas cardiopathy (CCC), which may be associated with cardiac arrhythmias, frequently use amiodarone, an antiarrhythmic drug that, experimentally, appears to modulate the cardiac autonomic function.

Objective: The present cross-sectional observational study aimed to evaluate autonomic cardiac modulation in patients with CCC undergoing chronic amiodarone therapy.

Methods: Three groups were investigated: Group 1 included patients with CCC not treated with amiodarone (n = 27); Group 2 included patients with CCC with prolonged use (at least 6 months) of amiodarone (n = 16); and Group 3 included non-Chagasic control patients (n = 23). All patients underwent a complete clinical and laboratory assessment, followed by autonomic function tests, consisting of a basal continuous electrocardiogram in the resting supine position for 10 minutes, followed by a change the orthostatic posture for a further 5 minutes. Heart rate variability (HRV) parameters (median and interquartile interval) were quantified using linear methods in the time- and frequency-domains (autoregressive spectral analysis) and nonlinear methods, including symbolic analysis.

Results: Patients with CCC using amiodarone had changes in HRV suggestive of an offset in the sympatho-vagal balance with a vagal modulation predominance (normalized HF, 49.7[27.4] vs 31.1[22.8] [P < 0.05]; and percentage 2V, 40.1 [14.6] vs 21.5 [13.4] [P < 0.05] vs untreated CCC group). These changes were further accompanied by increases in parameters indicative of greater complexity of HRV.

Conclusions: The deviation in the sympatho-vagal balance and the increase in the complexity of HRV strongly suggest that amiodarone may have a cardioprotective effect, in addition to its antiarrhythmic effects, which could increase the survival of these patients.
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http://dx.doi.org/10.1111/pace.13384DOI Listing
July 2018

Reference values for short-term resting-state heart rate variability in healthy adults: Results from the Brazilian Longitudinal Study of Adult Health-ELSA-Brasil study.

Psychophysiology 2018 06 2;55(6):e13052. Epub 2018 Jan 2.

Department of Physiological Sciences, Federal University of Espírito Santo, Center of Health Sciences, Vitória, Brazil.

Heart rate variability (HRV) is a psychophysiological phenomenon with broad implications, providing an accessible index of vagal function, underpinning psychological constructs, including the capacity for social engagement and emotion regulation, and may predict future morbidity and mortality. However, the lack of reference values for short-term HRV indices for participants of both sexes across the age spectrum is a limiting factor. This was the objective of the present study. Resting electrocardiographic records were obtained from 13,214 participants (both sexes, 35-74 years), and HRV indices in time and frequency domains (mean ± SD) were determined from 5-min records. Results were based on a subsample of 2,874 nonmedicated, healthy participants stratified by sex across 10-year age groupings. Men showed lower heart rate (HR, 64 ± 8 bpm vs. 68 ± 8 bpm, p < .05) and normalized high frequency (HF; 39.4 ± 18.0 normalized units [n.u.] vs. 50.4 ± 18.5 n.u., p < .05) than women, and higher N-N variance (2,214 ± 1,890 ms vs. 1,883 ± 1,635 ms , p < .05), standard deviation of all N-N intervals (SDNN; 43.7 ± 17.3 ms vs. 40.3 ± 15.8 ms, p < .05) and LF/HF (2.30 ± 2.68 vs. 1.33 ± 1.82, p < .05). HR and HF (n.u.) were also higher in younger than older women. LF/HF was lower in women than men. Percentile curves showed almost all HRV indices decreasing with aging. The availability of short-term, resting-state HRV reference values in a large sample of healthy and nonmedicated participants from 35-74 years will provide a valuable tool for researchers, clinicians, and those in the quantified-self community.
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http://dx.doi.org/10.1111/psyp.13052DOI Listing
June 2018

Long-term anabolic steroids in male bodybuilders induce cardiovascular structural and autonomic abnormalities.

Clin Auton Res 2018 04 10;28(2):231-244. Epub 2017 Oct 10.

Department of Physiology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.

Objective: The aims of this study were to examine the hypothesis that users of anabolic androgenic steroids (AAS) would have cardiac autonomic disorders and that there is a correlation between sympathetic modulation, high blood pressure (BP) and alterations to cardiac dimensions.

Methods: Forty-five male subjects were enrolled in the study. They were categorized into three groups comprising bodybuilders actively using AAS (AAS users; n = 15), bodybuilders who had never used AAS (nonusers; n = 15) and age-paired healthy sedentary controls (n = 15). Hemodynamic parameters, linear and nonlinear analyses of heart rate variability and electrocardiography and echocardiography analyses were performed at rest.

Results: Bodybuilders in the AAS group had a higher mean BP than those in the ASS nonuser group (p < 0.05) and the sedentary controls (p < 0.001). Cardiac sympathetic modulation was higher in AAS users than in AAS nonusers (p < 0.05) and the sedentary controls (p < 0.001), and parasympathetic modulation was lower in AAS users than in nonusers and the sedentary controls (p < 0.05). Shannon entropy was lower in AAS users than in the sedentary (p < 0.05) controls, and the corrected QT interval and QT dispersion were higher in AAS users than in the sedentary controls (p < 0.05). The interventricular septal thickness, left ventricle posterior wall thickness and relative diastolic wall thickness were higher in AAS users than in AAS nonusers and the sedentary controls (p < 0.001). AAS users showed a positive correlation between increased sympathetic modulation and high BP (r = 0.48, p < 0.005), as well as sympathetic modulation and cardiac hypertrophy (r = 0.66, p < 0.001).

Conclusion: There was a marked cardiac autonomic alteration in AAS users, with a shift toward sympathetic modulation predominance and vagal attenuation. The high BP observed in our group of bodybuilders using AAS was associated with increased sympathetic modulation, and this increased sympathetic modulation was associated with structural alterations in the heart. This association may constitute an important mechanism linking AAS abuse to increased cardiovascular risk.
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http://dx.doi.org/10.1007/s10286-017-0470-2DOI Listing
April 2018

Exercise training improves hypertension-induced autonomic dysfunction without influencing properties of peripheral cardiac vagus nerve.

Auton Neurosci 2017 12 14;208:66-72. Epub 2017 Sep 14.

Department of Physiology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro, Uberaba, Brazil.

We examined the vagal transfer function of autonomic heart rate (HR) control in anesthetized sedentary and exercise-trained Spontaneously Hypertensive Rats (SHR). To this end, male SHR and Wystar-Kyoto (WKY) rats with 48-50weeks of age-old were divided into 4 groups: sedentary (SHR, n=12) and trained (SHR, n=14) hypertensive rats, sedentary (WKY, n=13) and trained (WKY, n=13) normotensive rats. The trained groups were submitted to swimming protocol for 9weeks. Blood pressure (BP), HR, HR variability (HRV), BP variability (BPV), baroreflex sensitivity and cardiac tonus were recorded in baseline conditions. Following, electric stimulation of peripheral vagus nerve was performed in anesthetized conditions. Resting bradycardia was observed in SHR and WKY when compared to their respective sedentary groups (p<0.001). The BP was lower in SHR than in SHR (p<0.001). The SHR and WKY rats showed higher baroreflex-mediated tachycardia values when compared to their respective sedentary counterparts (p<0.001). Baroreflex bradycardic response in SHR was higher than in SHR (p<0.005). The SHR and WKY rats showed a decreased sympathetic activity in comparison to their respective sedentary groups (p<0.05). The cardiac vagal tonus was higher in SHR than in SHR (p<0.05). Regarding the dynamic transducer properties of peripheral vagus nerve to the heart no difference was observed among the groups. In conclusion, our results demonstrate that exercise training decreased BP in SHR and improved cardiovascular autonomic balance to the heart without changes in transduction properties of peripheral cardiac vagus nerve.
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http://dx.doi.org/10.1016/j.autneu.2017.09.012DOI Listing
December 2017

Biological properties of cardiac mesenchymal stem cells in rats with diabetic cardiomyopathy.

Life Sci 2017 Nov 1;188:45-52. Epub 2017 Sep 1.

Department of Physiology, Biological and Natural Sciences Institute, Triangulo Mineiro Federal University, Uberaba, MG, Brazil; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, RJ, Brazil. Electronic address:

Cardiomyopathy is a major outcome in patients with diabetes mellitus (DM) and contributes to the high morbidity/mortality observed in this disease.

Aims: To evaluate several biological properties of cardiac mesenchymal stem cells (cMSCs) in a rat model of streptozotocin-induced DM with concomitant diabetic cardiomyopathy.

Main Methods: After 10weeks of DM induction, diabetic and control rats were assessed using ECG and ventricular hemodynamics monitoring. Then, the hearts were excised and processed for histology and for extracting non-cardiomyocytic cells. A pool of these cells was plated for a colony forming units-fibroblasts (CFU-F) assay in order to estimate the number of cMSCs. The remaining cells were expanded to assess their proliferation rate as well as their osteogenic and adipogenic differentiation ability.

Key Findings: DM rats presented intense hyperglycemia and changes in ECG, LV hemodynamic, cardiac mass index and fibrosis, indicating presence of DCM. The CFU-F assay revealed a higher number of cardiac CFU-Fs in DM rats (10.4±1.1CFU-F/10 total cells versus 7.6±0.7CFU-F/10 total cells in control rats, p<0.05), which was associated with a significantly higher proliferative rate of cMSCs in DM rats. In contrast, cMSCs from DM rats presented a lower capacity to differentiate into both osteogenic (20.8±4.2% versus 10.1±1.0% in control rats, p<0.05) and adipogenic lineages (4.6±1.0% versus 1.3±0.5% in control rats, p<0.05).

Significance: The findings suggest, for the first time, that in chronic DM rats with overt DCM, cMSCs increase in number and exhibit changes in several functional properties, which could be implicated in the pathogenesis of diabetic cardiomyopathy.
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http://dx.doi.org/10.1016/j.lfs.2017.08.034DOI Listing
November 2017

Amiodarone and itraconazole improve the activity of pentavalent antimonial in the treatment of experimental cutaneous leishmaniasis.

Int J Antimicrob Agents 2017 Aug 28;50(2):159-165. Epub 2017 Jun 28.

Laboratório de Parasitologia, Universidade Federal do Triângulo Mineiro, Av Getúlio Guarita S/N, Abadia, 38001-970, Uberaba, Minas Gerais, Brazil.

Leishmaniasis affect millions of people, causing morbidity and mortality, especially in developing tropical and subtropical countries. Unfortunately, the possibilities of treatment for these infections are still quite limited and most of the available drugs present serious side effects. The objective of this paper was to evaluate the therapeutic role of amiodarone and itraconazole in the treatment of cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis. In order to perform this evaluation, hamsters were infected with 1 × 10 metaciclic promastigotes of the parasite in the hind footpad and, after the onset of the lesions, were treated with glucantime, amiodarone, itraconazole, glucantime and amiodarone, glucantime and itraconazole or amiodarone and itraconazole. The treatments' efficacy was evaluated per analysis of the size of the cutaneous lesions and by parasitic investigation of the infected foot (by histopathological examination and PCR) and possible side effects were analyzed taking into account the weight of the animals and some biochemical and metabolic parameters (glucose, urea, creatinine, AST, ALT and ALP). The results have shown that, in hamsters, amiodarone and itraconazole, either used isolated or in combination, are unable to stop the development of cutaneous lesions caused by L. (L.) amazonensis, but improve the activity of glucantime in the treatment of these lesions and seem to present no evident side effects. More studies are necessary in order to investigate the clinical potential of these combinations, so there can be the possibility of broadening the therapeutic options available, especially in resistant cases.
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http://dx.doi.org/10.1016/j.ijantimicag.2017.06.007DOI Listing
August 2017

Comparison between symbolic and spectral analyses of short-term heart rate variability in a subsample of the ELSA-Brasil study.

Physiol Meas 2015 Oct 3;36(10):2119-34. Epub 2015 Sep 3.

Collegiate of Biological Sciences, Federal University of Vale do São Francisco, Rod. BR 407 Km 12 Lote 543 Projeto de Irrigação Senador Nilo Coelho, s/nº-C1, CEP 56.300-990, Petrolina-PE, Brazil.

Linear and nonlinear analyses of heart rate variability (HRV) have been largely used to evaluate the autonomic balance directed to the cardiovascular system. However, comparative studies evaluating the agreement between methods are scarce. Therefore, our aim was to examine the relationship between spectral (SPA; linear) and symbolic analyses (SYA; nonlinear) indexes. A subsample of 683 participants of the Brazilian Longitudinal Study of Adult Health was investigated. Linear and nonlinear analyses were obtained from 10 min ECG recording at rest. Reliability and agreement between methods were evaluated by kappa-statistic and proportion of agreement. According to SYA, the most frequent pattern was P1V (sympathovagal balance, without sympathetic or vagal predominance) comprising 62.7% of the sample, followed by P2V (vagal predominance) with 33.2%, and finally P0V pattern (sympathetic predominance) with 4.1%. Overall proportion of agreement between SYA and SPA was 39.68% (95% CI 0.360-0.433), with expected agreement by chance of 30.8%. Kappa value was 0.128 indicating a slight agreement between methods. Proportion of agreement was 7.93% (95% CI 0.032-0.126) for predominant sympathetic modulation, 10.39% (95% CI 0.075-0.132) for sympathovagal modulation, and 40.29% (95% CI 0.361-0.444) for parasympathetic modulation. Our data provide evidence for important differences between SPA and SYA on HRV analysis. More studies are needed to clarify the causes of disagreement between two methods designed to evaluate the autonomic modulation of heart beats.
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http://dx.doi.org/10.1088/0967-3334/36/10/2119DOI Listing
October 2015

Priming Mesenchymal Stem Cells with Endothelial Growth Medium Boosts Stem Cell Therapy for Systemic Arterial Hypertension.

Stem Cells Int 2015 2;2015:685383. Epub 2015 Aug 2.

Physiology Division, Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, 38025-015 Uberaba, MG, Brazil.

Systemic arterial hypertension (SAH), a clinical syndrome characterized by persistent elevation of arterial pressure, is often associated with abnormalities such as microvascular rarefaction, defective angiogenesis, and endothelial dysfunction. Mesenchymal stem cells (MSCs), which normally induce angiogenesis and improve endothelial function, are defective in SAH. The central aim of this study was to evaluate whether priming of MSCs with endothelial growth medium (EGM-2) increases their therapeutic effects in spontaneously hypertensive rats (SHRs). Adult female SHRs were administered an intraperitoneal injection of vehicle solution (n = 10), MSCs cultured in conventional medium (DMEM plus 10% FBS, n = 11), or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC, n = 10). Priming of the MSCs reduced the basal cell death rate in vitro. The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups. The transplanted cells were rarely found in the hearts and kidneys. Taken together, our findings indicate that priming of MSCs boosts stem cell therapy for the treatment of SAH.
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http://dx.doi.org/10.1155/2015/685383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537741PMC
August 2015

Modulation of sympathetic activity and heart rate variability by ivabradine.

Cardiovasc Res 2015 Oct 22;108(1):31-8. Epub 2015 Jun 22.

Department of Biotechnology and Bioscience, University of Milan-Bicocca, P.za Della Scienza 2, Milan 20126, Italy

Aims: Bradycardic agents are currently used in the treatment of angina and heart failure; direct information on their effects on cardiac sympathetic nerve activity (SNA) may be relevant to their chronic use. The present study evaluates the effect of pacemaker inhibition on SNA; direct nerve recordings and indirect autonomic indexes are compared.

Methods And Results: Experiments were performed in 18 anaesthetized rats. SNA (direct nerve recording) and heart rate variability (HRV) indexes were evaluated in parallel. All parameters were recorded 10 min before to 60 min after administration of the If blocker ivabradine (IVA; 2 mg/kg, i.v.; n = 8) or vehicle (VEH; n = 5). IVA-induced RR interval (RR) prolongation (at 60 min +15.0 ± 7.1%, P < 0.01) was associated with decreased diastolic arterial pressure (DAP; -17.3 ± 8.4%, P < 0.05) and increased SNA (+51.1 ± 12.3%, P < 0.05). These effects were accompanied by increased RR variance (RRσ(2)), which showed strong positive correlation with RR. Frequency-domain HRV indexes (in normalized units) were unchanged by IVA. After baroreceptor reflexes had been eliminated by sino-aortic denervation (n = 5), similar IVA-induced RR prolongation (at 60 min +14.3 ± 5.9%, NS vs. intact) was associated with a larger DAP reduction (-30.9 ± 4.1%, P < 0.05 vs. intact), but failed to affect SNA.

Conclusions: (i) IVA-induced bradycardia was associated with increased SNA, resulting from baroreceptor unloading; if this applied to chronic IVA use in humans, it would be of relevance for therapeutic use of the drug. (ii) Whenever mean HR is concomitantly changed, time-domain HRV indexes should not be unequivocally interpreted in terms of autonomic balance.
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http://dx.doi.org/10.1093/cvr/cvv180DOI Listing
October 2015

Endogenous resident c-Kit cardiac stem cells increase in mice with an exercise-induced, physiologically hypertrophied heart.

Stem Cell Res 2015 Jul 27;15(1):151-64. Epub 2015 May 27.

Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil. Electronic address:

Physical activity evokes well-known adaptations in the cardiovascular system. Although exercise training induces cardiac remodeling, whether multipotent stem cells play a functional role in the hypertrophic process remains unknown. To evaluate this possibility, C57BL/6 mice were subjected to swimming training aimed at achieving cardiac hypertrophy, which was morphologically and electrocardiographically characterized. Subsequently, c-Kit(+)Lin(-) and Sca-1(+)Lin(-) cardiac stem cells (CSCs) were quantified using flow cytometry while cardiac muscle-derived stromal cells (CMSCs, also known as cardiac-derived mesenchymal stem cells) were assessed using in vitro colony-forming unit fibroblast assay (CFU-F). Only the number of c-Kit(+)Lin(-) cells increased in the hypertrophied heart. To investigate a possible extracardiac origin of these cells, a parabiotic eGFP transgenic/wild-type mouse model was used. The parabiotic pairs were subjected to swimming, and the wild-type heart in particular was tested for eGFP(+) stem cells. The results revealed a negligible number of extracardiac stem cells in the heart, allowing us to infer a cardiac origin for the increased amount of detected c-Kit(+) cells. In conclusion, the number of resident Sca-1(+)Lin(-) cells and CMSCs was not changed, whereas the number of c-Kit(+)Lin(-) cells was increased during physiological cardiac hypertrophy. These c-Kit(+)Lin(-) CSCs may contribute to the physiological cardiac remodeling that result from exercise training.
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http://dx.doi.org/10.1016/j.scr.2015.05.011DOI Listing
July 2015

Effects of cholinergic stimulation with pyridostigmine bromide on chronic chagasic cardiomyopathic mice.

Mediators Inflamm 2014 24;2014:475946. Epub 2014 Aug 24.

Natural and Biological Sciences Institute, Triangulo Mineiro Federal University, Praca Manoel Terra 330, Centro, 38025-015 Uberaba, MG, Brazil.

The aim of the present study was to assess the effects of an anticholinesterase agent, pyridostigmine bromide (Pyrido), on experimental chronic Chagas heart disease in mice. To this end, male C57BL/6J mice noninfected (control:Con) or chronically infected (5 months) with Trypanosoma cruzi (chagasic:Chg) were treated or not (NT) with Pyrido for one month. At the end of this period, electrocardiogram (ECG); cardiac autonomic function; heart histopathology; serum cytokines; and the presence of blood and tissue parasites by means of immunohistochemistry and PCR were assessed. In NT-Chg mice, significant changes in the electrocardiographic, autonomic, and cardiac histopathological profiles were observed confirming a chronic inflammatory response. Treatment with Pyrido in Chagasic mice caused a significant reduction of myocardial inflammatory infiltration, fibrosis, and hypertrophy, which was accompanied by a decrease in serum levels of IFNγ with no change in IL-10 levels, suggesting a shift of immune response toward an anti-inflammatory profile. Lower nondifferent numbers of parasite DNA copies were observed in both treated and nontreated chagasic mice. In conclusion, our findings confirm the marked neuroimmunomodulatory role played by the parasympathetic autonomic nervous system in the evolution of the inflammatory-immune response to T. cruzi during experimental chronic Chagas heart disease in mice.
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http://dx.doi.org/10.1155/2014/475946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4158292PMC
May 2015

Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson's disease: a comparison study of mononuclear and mesenchymal stem cells.

Int J Med Sci 2014 3;11(10):1049-64. Epub 2014 Aug 3.

1. Department of Pharmacology, Paraná Federal University, Curitiba, Paraná, Brazil;

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the injury site and prevents neuronal damage after an MPTP infusion could be considered as a potential treatment for PD during the early stage of disease development.
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http://dx.doi.org/10.7150/ijms.8182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135227PMC
March 2015

Remodeling of elastic layer of aortic artery after training by swimming in spontaneously hypertensive rats.

Exp Biol Med (Maywood) 2013 Jan;238(1):7-11

Discipline of General Pathology, Biological Sciences Department of Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil.

Hypertension is a major risk factor for cardiovascular diseases, in which the elastic properties of arteries are subjected to high pressure levels, and networks of elastic fibers may develop cleft longitudinal, transverse, breaks and fragmentation, and such structural changes (fibrosis and degradation of elastin) may lead to a decrease in the elasticity of the artery. The descending thoracic aortas of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHRs) subjected to physical training through swimming or those of sedentary rats were prepared with hematoxylin-eosin and Verhoff to assess the artery medial. The images were captured with a videocamera coupled to an ordinary light microscope and the images were analyzed with the same program. SHRs showed a larger area of the medial layer of the thoracic aorta (F = 25,764, P < 0.001), and it was observed that rats submitted to physical training through swimming showed a larger area of the thoracic aorta (t = 3.206, P = 0.011). There was a higher percentage of elastic trained (F = 6.536, P = 0.019). To conclude, this study aimed to determine the elastic component of the aortic artery in animals that underwent exercise when compared with those that did not perform the activity, and analyze the relationship between the area of the aortic wall in trained and sedentary animals. The principal conclusion is that the rigidity of the aorta is not increased in SHRs subjected to physical training compared with that of trained WKY animals; however, when sedentary SHRs were analyzed there was a decrease in the elasticcomponent, which can characterize the aortic arterial stiffness in SHRs.
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http://dx.doi.org/10.1258/ebm.2012.012243DOI Listing
January 2013

Symptoms of anxiety and mood disturbance alter cardiac and peripheral autonomic control in patients with metabolic syndrome.

Eur J Appl Physiol 2013 Mar 24;113(3):671-9. Epub 2012 Aug 24.

Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil.

Previous investigations show that metabolic syndrome (MetSyn) causes sympathetic hyperactivation. Symptoms of anxiety and mood disturbance (AMd) provoke sympatho-vagal imbalance. We hypothesized that AMd would alter even further the autonomic function in patients with MetSyn. Twenty-six never-treated patients with MetSyn (ATP-III) were allocated to two groups, according to the levels of anxiety and mood disturbance: (1) with AMd (MetSyn + AMd, n = 15), and (2) without AMd (MetSyn, n = 11). Ten healthy control subjects were also studied (C, n = 10). AMd was determined using quantitative questionnaires. Muscle sympathetic nerve activity (MSNA, microneurography), blood pressure (oscillometric beat-to-beat basis), and heart rate (ECG) were measured during a baseline 10-min period. Spectral analysis of RR interval and systolic arterial pressure were analyzed, and the power of low (LF) and high (HF) frequency bands were determined. Sympatho-vagal balance was obtained by LF/HF ratio. Spontaneous baroreflex sensitivity (BRS) was evaluated by calculation of α-index. MSNA was greater in patients with MetSyn + AMd compared with MetSyn and C. Patients with MetSyn + AMd showed higher LF and lower HF power compared with MetSyn and C. In addition, LF/HF balance was higher in MetSyn + AMd than in MetSyn and C groups. BRS was decreased in MetSyn + AMd compared with MetSyn and C groups. Anxiety and mood disturbance alter autonomic function in patients with MetSyn. This autonomic dysfunction may contribute to the increased cardiovascular risk observed in patients with mood alterations.
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http://dx.doi.org/10.1007/s00421-012-2476-8DOI Listing
March 2013

Autonomic nervous system modulation affects the inflammatory immune response in mice with acute Chagas disease.

Exp Physiol 2012 Nov 15;97(11):1186-202. Epub 2012 Jun 15.

Biological Sciences Institute, Triangulo Mineiro Federal University, Uberaba, MG, Brazil.

The aim of the present study was to evaluate the effects of changes to the autonomic nervous system in mice during the acute phase of Chagas disease, which is an infection caused by the parasite Trypanosoma cruzi. The following types of mice were inoculated with T. cruzi (CHG): wild-type (WT) and vesicular acetylcholine transporter knockdown (KDVAChT) C57BL/6j mice; wild-type non-treated (NT) FVB mice; FVB mice treated with pyridostigmine bromide (PYR) or salbutamol (SALB); and β(2)-adrenergic receptor knockout (KOβ2) FVB mice. During infection and at 18-21 days after infection (acute phase), the survival curves, parasitaemia, electrocardiograms, heart rate variability, autonomic tonus and histopathology of the animals were evaluated. Negative control groups were matched for age, genetic background and treatment. The KDVAChT-CHG mice exhibited a significant shift in the electrocardiographic, autonomic and histopathological profiles towards a greater inflammatory immune response that was associated with a reduction in blood and tissue parasitism. In contrast, the CHG-PYR mice manifested reduced myocardial inflammation and lower blood and tissue parasitism. Similar results were observed in CHG-SALB animals. Unexpectedly, the KOβ2-CHG mice exhibited less myocardial inflammation and higher blood and tissue parasitism, which were associated with reduced mortality. These findings could have been due to the increase in vagal tone observed in the KOβ2 mice, which rendered them more similar to the CHG-PYR animals. In conclusion, our results indicate a marked immunomodulatory role for the parasympathetic and sympathetic autonomic nervous systems, which inhibit both the inflammatory immune response and parasite clearance during the acute phase of experimental Chagas heart disease in mice.
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http://dx.doi.org/10.1113/expphysiol.2012.066431DOI Listing
November 2012

Autonomic neuroimmunomodulation in chagasic cardiomyopathy.

Exp Physiol 2012 Nov 11;97(11):1151-60. Epub 2012 May 11.

Department of Biological Sciences, Triangulo Mineiro Federal University, Uberaba, MG, Brazil.

Chagas disease is an endemic parasitic disease, caused by the flagellate protozoan Trypanosoma cruzi, with a high prevalence in Latin America. During its chronic phase, chronic chagasic cardiomyopathy is the most apparent clinical form, affecting 25-30% of patients. This clinical form may present as congestive heart failure, thromboembolic phenomena, cardiac arrhythmias and sudden death. Pathological findings in the heart include mononuclear inflammatory infiltrate, focal myocarditis, epicarditis and neuroganglionitis, associated with variable focal fibrosis and widely variable autonomic dysfunction. The immune-inflammatory response has been considered to be the cause of the autonomic dysfunction, which may trigger life-threatening arrhythmias and sudden death. In the last few years, several reports in the literature have described the marked role played by the autonomic nervous system in the modulation of the immune-inflammatory response in some experimental models of infectious, ischaemic and autoimmune diseases. However, nothing is known about this autonomic neural modulation of the immune response in Chagas disease. In the present report, we discuss several sets of evidence suggesting that changes in the autonomic drive directed towards the heart could modify blood and tissue parasitism, as well as inflammatory infiltration, in chagasic cardiomyopathy. The pathogenic implications of these potential neural immune manipulations are also discussed.
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http://dx.doi.org/10.1113/expphysiol.2012.066381DOI Listing
November 2012

Exercise-training reduced blood pressure and improve placental vascularization in pregnant spontaneously hypertensive rats--pilot study.

Fetal Pediatr Pathol 2012 Dec 16;31(6):423-31. Epub 2012 Apr 16.

Institute of Biological and Natural Sciences, Federal University of the Triângulo Mineiro (UFTM) , Uberaba , Brazil.

Assess the effects of exercise-training on resting arterial pressure and heart rate, placental fetuses morphologic alterations in pregnant spontaneously hypertensive rats (SHRs).Twenty SHRs and their respective control normotensive rats (WKY) were submitted or not to a swimming protocol during 9 weeks, resulting in four pregnant experimental groups: sedentary hypertensive (PSH), trained hypertensive (PTH), sedentary normotensive (PSN), and trained normotensive (PTN). Exercise-training by swimming attenuates arterial pressure in pregnant SHRs, and can contribute to an increase in the length of fetuses and the percentage of the vessels in the placenta.
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http://dx.doi.org/10.3109/15513815.2012.659535DOI Listing
December 2012

Acute adenosine increases cardiac vagal and reduces sympathetic efferent nerve activities in rats.

Exp Physiol 2012 Jun 24;97(6):719-29. Epub 2012 Feb 24.

Department of Clinical Sciences, University of Milan, Internal Medicine II, L. Sacco Hospital, Milan, Italy.

Adenosine is the first drug of choice in the treatment of supraventricular arrhythmias. While the effects of adenosine on sympathetic nerve activity (SNA) have been investigated, no information is available on the effects on cardiac vagal nerve activity (VNA). We assessed in rats the responses of cardiac VNA, SNA and cardiovascular variables to intravenous bolus administration of adenosine. In 34 urethane-anaesthetized rats, cardiac VNA or cervical preganglionic sympathetic fibres were recorded together with ECG, arterial pressure and ventilation, before and after administration of three doses of adenosine (100, 500 and 1000 μg kg(-1)). The effects of adenosine were also assessed in isolated perfused hearts (n = 5). Adenosine induced marked bradycardia and hypotension, associated with a significant dose-dependent increase in VNA (+204 ± 56%, P < 0.01; +275 ± 120%, P < 0.01; and +372 ± 78%, P < 0.01, for the three doses, respectively; n = 7). Muscarinic blockade by atropine (5 mg kg(-1), i.v.) significantly blunted the adenosine-induced bradycardia (-56.0 ± 4.5%, P < 0.05; -86.2 ± 10.5%, P < 0.01; and -34.3 ± 9.7%, P < 0.01, respectively). Likewise, adenosine-induced bradycardia was markedly less in isolated heart preparations. Previous barodenervation did not modify the effects of adenosine on VNA. On the SNA side, adenosine administration was associated with a dose-dependent biphasic response, including overactivation in the first few seconds followed by a later profound SNA reduction. Earliest sympathetic activation was abolished by barodenervation, while subsequent sympathetic withdrawal was affected neither by baro- nor by chemodenervation. This is the first demonstration that acute adenosine is able to activate cardiac VNA, possibly through a central action. This increase in vagal outflow could make an important contribution to the antiarrhythmic action of this substance.
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http://dx.doi.org/10.1113/expphysiol.2011.063925DOI Listing
June 2012

The relationship between heart rate variability and serum cytokines in chronic chagasic patients with persistent parasitemia.

Pacing Clin Electrophysiol 2011 Jun 28;34(6):724-35. Epub 2011 Jan 28.

Internal Medicine Department, Infectious Division, Federal University of the Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.

Background: Persistent parasitemia, immunological, and autonomic nervous system impairments may play an important role in the evolution and clinical outcome of the chronic phase of Chagas' disease by triggering functional cardiovascular changes.

Methods: Three groups were evaluated: 17 chronic chagasic patients with the indeterminate form (IChD), 12 chronic chagasic patients with cardiac forms (ChHD), and 29 individuals as a healthy control group. Parasitemia was assessed by polymerase chain reaction; hemoculture, heart rate variability by linear and nonlinear methods, and interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, and tumor necrosis factor-α, and interferon (IFN)-γ serum cytokines were assessed by enzyme-linked immune assay.

Results: Twenty-nine chronic chagasic patients were positive for parasitemia (17 IChD and 12 ChHD). Heart rate variability parameters in baseline condition and after cold face test were significantly decreased in chagasic patients compared to controls. Tilt tests showed no alteration. However, using nonlinear indices, ChHD patients presented lower values compared to IChD and controls. Differences in the expression of serum cytokines were observed between chagasic patients and controls. However, among the groups, ChHD presented higher median values of IL-10 and lower of IFN-γ compared to IChD.

Conclusion: Both chagasic groups present an autonomic impairment using linear methods. The nonlinear methods revealed that the ChHD group had a higher cardiovascular risk. Serum cytokine concentrations between chagasic patients were similar. However, ChHD showed higher concentrations of IL-10 and lower of IFN-γ, suggesting some established process of immune regulation.
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http://dx.doi.org/10.1111/j.1540-8159.2010.03025.xDOI Listing
June 2011

Heart rate and arterial pressure variability and baroreflex sensitivity in ovariectomized spontaneously hypertensive rats.

Life Sci 2009 May 26;84(21-22):719-24. Epub 2009 Feb 26.

Department of Biological Sciences, School of Medicine, Federal University of the Triangulo Mineiro, Praça Manoel Terra, 330, Uberaba, MG 38015-050, Brazil.

Aims: The present study evaluated the effects of ovariectomy on heart rate and arterial pressure variability and cardiac baroreflex sensitivity (BRS) in female spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY).

Main Methods: Sham-surgery animals were used as control. Sixteen weeks after ovariectomy or sham-surgery, animals were recorded. Time series of pulse interval (PI) and systolic AP (SAP) were analyzed by means of autoregressive spectral analysis, which quantifies the power of very low (VLF=0.01-0.25 Hz), low (LF=0.25-0.75 Hz) and high frequency (HF=0.75-2.5 Hz) bands. BRS was assessed by means of linear regression between changes of PI and SAP induced by vasoactive drugs or calculation of alpha-index, a spontaneous BRS index.

Key Findings: There was no difference in baseline PI or SAP between ovariectomized and sham SHR. Spectral analysis of heart rate variability suggested a shift of sympatho-vagal balance toward sympathetic predominance in ovariectomized SHR (LF/HF=1.8+/-0.2 versus 0.7+/-0.2 in sham SHR, p<0.05). Ovariectomy increased total variance and VLF power of SAP in SHR (29.1+/-9.6 mmHg2 and 18.6+/-6.3 mmHg2 versus 9.1+/-2.1 mmHg2 and 4.3+/-1.4 mmHg2, respectively, in sham SHR, p<0.05). In addition, ovariectomy reduced reflex bradycardia in SHR (0.18+/-0.03 ms/mmHg versus 0.34+/-0.06 ms/mmHg in sham SHR, p<0.05). Ovariectomy did not affect heart rate and SAP variability or BRS in WKY.

Significance: These data showed that ovarian hormones deprivation induced marked changes on cardiovascular control, increasing SAP variability and cardiac sympatho-vagal balance and blunting BRS in female hypertensive animals, which reinforce the possible protective role of ovarian hormones on the cardiovascular system.
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http://dx.doi.org/10.1016/j.lfs.2009.02.019DOI Listing
May 2009

Genotoxic studies in hypertensive and normotensive rats treated with amiodarone.

Mutat Res 2008 Dec 25;657(2):155-9. Epub 2008 Sep 25.

Depto. Ciências Biológicas, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.

Amiodarone, a benzofuran derivative, is a very effective antiarrhythmic medication, but has potential to cause side effects. Although its cytotoxicity potential is very well-known, there are few reports about its genotoxicity effects. Since amiodarone has not been investigated in genotoxicity studies, and the spontaneously hypertensive rat (SHR) is a well-characterized model for hypertension, the aim of the present study was to perform cytogenetic analysis on chromosome aberrations in bone marrow cells of SHRs and normotensive Wistar-Kyoto rats (WKYs) that received oral amiodarone treatment for 4 weeks. Amiodarone activity was also monitored using electrocardiograms. The presence of bradycardia in amiodarone-treated rats confirmed that this drug was really active. Metaphase analysis on bone marrow cells showed that there were significant differences in total chromosomal damage and percentage abnormal metaphase between WKY and SHR negative controls. In the SHR negative control, the frequencies of basal chromosomal aberrations and abnormal metaphases were significantly higher (p<0.05). There were high numbers of chromosomal aberrations in all amiodarone-treated groups, compared with negative controls. In amiodarone-treated groups, the most frequent chromosomal aberration was chromatid breaks. More chromosomal aberrations were found in WKYs that received amiodarone, with a statistically significant difference in comparison with negative controls (p<0.05). However, in SHR rats there was no significant difference between the amiodarone and negative groups regarding chromosomal damage induction. These results showed that treatment with amiodarone was genotoxic in WKYs, but not in SHRs. Further studies are needed to confirm whether amiodarone is genotoxic or efficient and harmless, among humans undergoing therapy.
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http://dx.doi.org/10.1016/j.mrgentox.2008.09.005DOI Listing
December 2008

Nitric oxide synthesis blockade increases hypertrophy and cardiac fibrosis in rats submitted to aerobic training.

Arq Bras Cardiol 2007 Aug;89(2):88-93, 99-104

Faculdade de Medicina de Ribeirão Preto, Universidade Estadual de Londrina, Uberaba, MG, Brazil.

Objective: The objective of the present study was to evaluate cardiac tissue adaptations in rats submitted to aerobic training after nitric oxide (NO) synthesis blockade.

Methods: The animals (n=48) were divided into four groups: sedentary (CONTROL group); hypertensive after administration of NG-nitro-L-arginine methyl ester for 7 days (L-NAME Group); trained for 8 weeks through swimming exercises (TRAINED Group);trained and treated with L-NAME during the last week (L-NAME TRAINED Group). All the animals were submitted to the experiment procedures for blood pressure (BP) readings and cardiac morphometric evaluation.

Results: In comparison to the other groups, the L-NAME and L-NAME TRAINED groups were hypertensive (p<0.05); however, BP elevation in the L-NAME TRAINED group was significantly lower than the L-NAME group (p<0.05). The heart weight indexes for the TRAINED and L-NAME TRAINED groups were higher than the CONTROL and L-NAME groups (p<0.05). Also they had presented higher rates of macroscopic cardiac area and cardiac fibrosis in relation to the rest (p<0.05); comparisons revealed that the values for the L-NAME TRAINED group were significantly higher (p<0.05) than the others.

Conclusion: Short term NO synthesis blockade in sedentary animals induced hypertension but did not cause cardiac hypertrophy. In the trained animals, the inhibition of NO synthesis attenuated hypertension, induced cardiac hypertrophy and significantly increased myocardial fibrosis, indicating that NO plays an important role in cardiac tissue adaptations caused by aerobic exercise.
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http://dx.doi.org/10.1590/s0066-782x2007001400005DOI Listing
August 2007

Cardiac autonomic function in chagasic elderly patients in an endemic area: A time and frequency domain analysis approach.

Auton Neurosci 2007 Jan 27;131(1-2):94-101. Epub 2006 Jun 27.

Division of Infectious Disease of Federal University of the Triângulo Mineiro, Uberaba, Minas Gerais State, Brazil.

Chagas' disease is a common cause of cardiac autonomic impairment. In an endemic area there is a predominance of the indeterminate form and the number of elderly individuals committed by the disease is increasing. This study aimed to investigate the profile of heart rate variability (HRV) in elderly chagasic patients. 28 aged chagasic (CH), 28 non-chagasic (NC) aged individuals and 28 adults between 20 and 40 years old (YG) were studied. R-R intervals were assessed in time and frequency domains applying an autoregressive algorithm. There was no difference regarding temporal and spectral indices among the elderly groups in baseline. The values of the variance in CH, NC and YG individuals were 891.80, 283.60, 2557.00, showing a reduction of the total HRV in the aged groups when compared to the young control (p < 0.001). During the cold face test, the pNN50 response was significantly different only in the young group (p < 0.001). The temporal and spectral indices were not different among the elderly groups. The percentile changes of the R-R intervals induced by the tilt test in CH, NC and YG were respectively -7.04%, -9.35%, -15.81%, being significantly higher in the young individuals (p < 0.001). There was no difference regarding the percentile changes of the temporal and spectral indices between CH and NC elderly patients. The cardiac autonomic function assessed by HRV parameters presented no differences among the elderly individuals (CH and NC) living in an endemic area.
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http://dx.doi.org/10.1016/j.autneu.2006.05.005DOI Listing
January 2007

Power spectral analysis of heart rate variability in HIV-infected and AIDS patients.

Pacing Clin Electrophysiol 2006 Jan;29(1):53-8

Infectious Diseases Division, Department of Internal Medicine, School of Medicine of the Triangulo Mineiro, Uberaba, MG, Brazil.

Background: In HIV-infected patients the risks for cardiovascular disease are multifactorial. Autonomic dysfunction has been detected in the early phase of HIV infection as well as in AIDS patients with advanced cardiomyopathy.

Methods: Forty AIDS patients receiving highly active antiretroviral therapy (HAART), 40 HIV+ naïve of HAART, and 40 control subjects were studied. Computerized analysis of heart rate variability was performed using an analog to digital converter. R-R intervals were obtained from a standard ECG, recorded in DII lead in supine rest and after the cold-face and tilt tests. The series of R-R intervals were assessed in time and frequency domains using an autoregressive algorithm.

Results: There was no difference regarding to mean values of R-R intervals and variance in baseline. The normalized power of the low-frequency (LF) component and the low-frequency/high-frequency (HF) ratio (LF/HF) was significantly decreased in the HIV group. Responses of normalized HF and LF/HF ratio during the cold-face test were significantly decreased in the HIV group, as compared to the control. During the tilt test, a higher augmentation of normalized LF and the LF/HF ratio was observed in the HIV group compared with the control. The AIDS group was similar to the control in baseline and after cold-face and tilt tests.

Conclusion: The HIV group presented in baseline conditions, a shift of cardiac sympathovagal balance, an exacerbated response of the LF component during the tilt test, and an ineffective cardiac vagal response to the cold-face test suggesting sympathetic and parasympathetic dysfunction. AIDS patients receiving HAART did not present these autonomic alterations.
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http://dx.doi.org/10.1111/j.1540-8159.2006.00297.xDOI Listing
January 2006

Effects of long-term angiotensin converting enzyme inhibition on cardiovascular variability in aging rats.

Auton Neurosci 2006 Jan 24;124(1-2):49-55. Epub 2006 Jan 24.

Department of Biological Sciences, School of Medicine of Triângulo Mineiro, Uberaba, MG Brazil.

We studied the effects of chronic (4 weeks) angiotensin converting enzyme inhibition with captopril on arterial pressure (AP) and heart rate (HR) variability, as well as on cardiac baroreflex sensitivity (BRS), in aged (20 months) rats. Series of basal RR interval (RRi) and systolic AP (SAP) were studied by autoregressive spectral analysis with oscillations quantified in low (LF: 0.2-0.8 Hz) and high frequency (HF: 0.8-2.5 Hz). BRS was measured by linear regression between HR and MAP changes. Captopril did not affect the spectra of RRi or SAP in young rats. Aged rats presented a reduction in variance (time domain) and in LF and HF oscillations of RRi and SAP. Captopril induced, in aged rats, a decrease in absolute and normalized LF oscillations and in LF/HF ratio of RRi. Captopril also reduced the variance, without changing its LF or HF components of SAP. Reflex tachycardia was reduced in aged as compared to young rats (-1.1+/-0.2 versus -3.4+/-0.5 bpm/mm Hg) and captopril did not affect it. Reflex bradycardia was also reduced in aged rats (-0.7+/-0.5 versus -2.0+/-0.4 bpm/mm Hg), but captopril prevented this attenuation in aged rats (-2.3+/-0.3 versus -0.7+/-0.5 bpm/mm Hg). These data indicate that there is a reduction in HR and SAP variability during aging, suggesting impairment of cardiovascular autonomic control. Captopril was able to change the power of oscillatory components of RRi, suggesting a shift in cardiac sympatho/vagal balance toward parasympathetic predominance. In addition, blockage of ACE improved the reflex bradycardia, but not the reflex tachycardia in aged rats.
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http://dx.doi.org/10.1016/j.autneu.2005.11.004DOI Listing
January 2006

Cardiac autonomic modulation in hypertensive patients with Chagas' disease.

Acta Trop 2006 Feb 13;97(2):188-95. Epub 2005 Dec 13.

Faculdade de Medicina do Triângulo Mineiro, Disciplina de Doenças Infecciosas e Parasitárias, Departamento de Clínica Médica, Avenida Getúlio Guarita, S/N, Caixa Postal: 118, Uberaba, Minas Gerais 38025-440, Brazil.

Background: Arterial hypertension and Chagas' disease are prevalent pathologies in Latin America. It has been demonstrated that each one of them may cause cardiac autonomic dysfunction. This study aimed to investigate the pattern of cardiac autonomic modulation in chagasic-hypertensive patients.

Methods: Subjects (n=120) without left ventricular dysfunction were distributed in four groups: healthy control (n=30); hypertensive (n=30); chagasic (n=30) and chagasic-hypertensive (n=30). Patients were evaluated by autoregressive spectral analysis of heart rate variability in three different conditions: baseline, cold face and passive tilt tests. Power spectral densities in low (0.04-0.15 Hz) and high (0.15-0.50 Hz) frequency bands were estimated in both absolute and normalized units.

Results: Baseline median values (percentile 25 to percentile 75) of mean arterial pressure (in mmHg) were 93.3 (85.0-96.7), 116.7 (*, #) (110.0-129.2), 86.7 (83.3-92.5) and 106.7 (*, #) (106.7-110.0) for healthy control, hypertensive, chagasic and chagasic-hypertensive patients, respectively (*p<0.05 versus healthy control, #p<0.05 against chagasic group). Heart rate at rest did not differ among groups. Regarding to spectral parameters in baseline conditions, the absolute power of high frequency component of heart rate variability of the chagasic-hypertensive group was significantly lower than that found in healthy control and hypertensive patients. There were no differences in spectral parameters responses during cold face test. After passive tilt test, however, decreases in high frequency oscillations and increases in sympathovagal balance (low and high frequency ratio) were significantly lower in hypertensive, chagasic and chagasic-hypertensive patients as compared with healthy control.

Conclusions: These data indicate that chagasic-hypertensive patients presented an impairment of cardiac parasympathetic modulation at baseline conditions as well as in response to passive orthostatic stress.
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http://dx.doi.org/10.1016/j.actatropica.2005.10.006DOI Listing
February 2006