Cardiorespiratory adaptations induced by aerobic training in middle-aged men: the importance of a decrease in sympathetic stimulation for the contribution of dynamic exercise tachycardia

We investigated the effects of aerobic training on the efferent autonomic control of heart rate (HR) during dynamic exercise in middle-aged men, eight of whom underwent exercise training (T) while the other seven continued their sedentary (S) life style. The training was conducted over 10 months (three 1-h sessions/week on a field track at 70-85% of the peak HR). The contribution of sympathetic and parasympathetic exercise tachycardia was determined in terms of differences in the time constant effects on the HR response obtained using a discontinuous protocol (4-min tests at 25, 50, 100 and 125 watts on a cycle ergometer), and a continuous protocol (25 watts/min until exhaustion) allowed the quantification of the parameters (anaerobic threshold, VO2 AT; peak O2 uptake, VO2 peak; power peak) that reflect oxygen transport. The results obtained for the S and the T groups were: 1) a smaller resting HR in T (66 beats/min) when compared to S (84 beats/min); 2) during exercise, a small increase in the fast tachycardia (D0-10 s) related to vagal withdrawal (P<0.05, only at 25 watts) was observed in T at all powers; at middle and higher powers a significant decrease (P<0.05 at 50, 100 and 125 watts) in the slow tachycardia (D1-4 min) related to a sympathetic-dependent mechanism was observed in T; 3) the VO2 AT (S = 1.06 and T = 1.33 l/min) and VO2 peak (S = 1.97 and T = 2.47 l/min) were higher in T (P<0.05). These results demonstrate that aerobic training can induce significant physiological adaptations in middle-aged men, mainly expressed as a decrease in the sympathetic effects on heart rate associated with an increase in oxygen transport during dynamic exercise.

Modulation of hormone secretion by functional electrical stimulation of the intact and incompletely dysfunctional dog pancreas

The purpose of the present study was to modulate the secretion of insulin and glucagon in Beagle dogs by stimulation of nerves innervating the intact and partly dysfunctional pancreas. Three 33-electrode spiral cuffs were implanted on the vagus, splanchnic and pancreatic nerves in each of two animals. Partial dysfunction of the pancreas was induced with alloxan. The nerves were stimulated using rectangular, charge-balanced, biphasic, and constant current pulses (200 µs, 1 mA, 20 Hz, with a 100-µs delay between biphasic phases). Blood samples from the femoral artery were drawn before the experiment, at the beginning of stimulation, after 5 min of stimulation, and 5 min after the end of stimulation. Radioimmunoassay data showed that in the intact pancreas stimulation of the vagal nerve increased insulin (+99.2 µU/ml) and glucagon (+18.7 pg/ml) secretion and decreased C-peptide secretion (-0.15 ng/ml). Splanchnic nerve stimulation increased insulin (+1.7 µU/ml), C-peptide (+0.01 ng/ml), and glucagon (+50 pg/ml) secretion, whereas pancreatic nerve stimulation did not cause a marked change in any of the three hormones. In the partly dysfunctional pancreas, vagus nerve stimulation increased insulin (+15.5 µU/ml), glucagon (+11 pg/ml), and C-peptide (+0.03 ng/ml) secretion. Splanchnic nerve stimulation reduced insulin secretion (-2.5 µU/ml) and increased glucagon (+58.7 pg/ml) and C-peptide (+0.39 ng/ml) secretion, and pancreatic nerve stimulation increased insulin (+0.2 µU/ml), glucagon (+5.2 pg/ml), and C-peptide (+0.08 ng/ml) secretion. It was concluded that vagal nerve stimulation can significantly increase insulin secretion for a prolonged period of time in intact and in partly dysfunctional pancreas.

Immunopathology of human schistosomiasis mansoni: II. NK activity and stimulation by specific antigen

Sixteen S. mansoni infected and untreated patients (5 with recent infection and 11 with chronic disease) were evaluated for their in vitro natural killer (NK) activity against the NK sensitive target K562 cell line. NK levels in 9 out of 11 patients (82%) with chronic disease were significantly lower (mean = 15 ± 6%),compared with patients recently infected (mean = 41 ± 9% p < 0.001) and with the control group (mean = 38 ± 13% p < 0.001). However, both patients and controls NK activity was stimulated by soluble adult worm antigens (SAWA), indicating that NK function even in the chronic stage of the infection is able to respond to the parasite antigens. These results suggest the possibility of NK cell participation as effector mechanism against S. mansoni.

Evaluation of CD4+CD25+ T lymphocyte response time kinetics in patients with chronic Chagas disease after in vitro stimulation with recombinant Trypanosoma cruzi antigens

Introduction CD4+CD25+ T lymphocytes have been implicated in the regulation of host inflammatory response against Trypanosoma cruzi, and may be involved in the clinical course of the disease. Methods Peripheral blood mononuclear cells from patients with chronic Chagas disease were cultured in the presence of T. cruzi recombinant antigens and assayed for lymphocytes at distinct time points. Results It was possible to differentiate clinical forms of chronic Chagas disease at days 3 and 5 according to presence of CD4+CD25+ T cells in cell cultures. Conclusions Longer periods of cell culture proved to be potentially valuable for prospective evaluations of CD4+CD25+ T lymphocytes in patients with chronic Chagas disease.

Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease patients with no apparent cardiac involvement

INTRODUCTION : Exercise-induced ventricular arrhythmia (EIVA) and autonomic imbalance are considered as early markers of heart disease in Chagas disease (ChD) patients. The objective of the present study was to verify the differences in the occurrence of EIVA and autonomic maneuver indexes between healthy individuals and ChD patients with no apparent cardiac involvement. METHODS : A total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5) years, and 38 healthy individuals, aged 44.0 (9.2) years, were evaluated using echocardiography, symptom-limited treadmill exercise testing and autonomic function tests. RESULTS : The occurrence of EIVA was higher in the chagasic group (48%) than in the control group (23.7%) during both the effort and the recovery phases. Frequent ventricular contractions occurred only in the patient group. Additionally, the respiratory sinus arrhythmia index was significantly lower in the chagasic individuals compared with the control group. CONCLUSIONS : ChD patients with no apparent cardiac involvement had a higher frequency of EIVA as well as more vagal dysfunction by respiratory sinus arrhythmia. These results suggest that even when asymptomatic, ChD patients possess important arrhythmogenic substrates and subclinical disease.

Cholinergic stimulation with pyridostigmine, hemodynamic and echocardiographic analysis in healthy subjects

OBJECTIVE: Growing evidence suggests that sudden death after an acute myocardial infarction (AMI) correlates with autonomic nervous system imbalance. Parasympathomimetic drugs have been tested to reverse these changes. However, their effects on ventricular function need specific evaluation. Our objective was to analyze pyridostigmine's (PYR) effect on hemodynamic and echocardiographic variables of ventricular function. METHODS: Twenty healthy volunteers underwent Doppler echocardiographic evaluations, blood pressure (BP), and heart rate (HR) assessment at rest, before and 120 min after ingestion of 30 mg PYR or placebo, according to a double-blind, placebo-controlled, crossed and randomized protocol, on different days. RESULTS: PYR was well tolerated and did not cause alterations in BP or in ventricular systolic function. A reduction in HR of 10.9±1.3% occurred (p<0,00001). There was an A wave reduction in the mitral flow (p<0.01) and an E/A ratio increase (p<0.001) without changes in the other diastolic function parameters (p>0.05). CONCLUSION: PYR reduces HR and increases E/A ratio, without hemodynamic impairment or ventricular function change.

Right ventricular bifocal stimulation in the treatment of dilated cardiomyopathy with heart failure

OBJECTIVE: To describe a new more efficient method of endocardial cardiac stimulation, which produces a narrower QRS without using the coronary sinus or cardiac veins. METHODS: We studied 5 patients with severe dilated cardiomyopathy, chronic atrial fibrillation and AV block, who underwent definitive endocardial pacemaker implantation, with 2 leads, in the RV, one in the apex and the other in the interventricular septum (sub pulmonary), connected, respectively, to ventricular and atrial bicameral pacemaker outputs. Using Doppler echocardiography, we compared, in the same patient, conventional (VVI), high septal ("AAI") and bifocal ("DDT" with AV interval ~ 0) stimulation. RESULTS: The RV bifocal stimulation had the best results with an increase in ejection fraction and cardiac output and reduction in QRS duration, mitral regurgitation and in the left atrium area (p <= 0.01). The conventional method of stimulation showed the worst result. CONCLUSION: These results suggest that, when left ventricular stimulation is not possible, right ventricular bifocal stimulation should be used in patients with severe cardiomyopathy where a pacemaker is indicated.

Exercise stress testing in healthy subjects during cholinergic stimulation after a single dose of pyridostigmine

OBJETIVE: The evaluation, by exercise stress testing, of the cardiorespiratory effects of pyridostigmine (PYR), a reversible acetylcholinesterase inhibitor. METHODS: A double-blind, randomized, cross-over, placebo-controlled comparison of hemodynamic and ventilation variables of 10 healthy subjects who underwent three exercise stress tests (the first for adaptation and determination of tolerance to exercise, the other two after administration of placebo or 45mg of PYR). RESULTS: Heart rate at rest was: 68±3 vs 68±3bpm before and after placebo, respectively (P=0.38); 70±2 vs 59±2bpm, before and after pyridostigmine, respectively (P<0.01). During exercise, relative to placebo: a significantly lower heart rate after PYR at, respectively, 20% (P=0.02), 40% (P=0.03), 80% (P=0.05) and 100% (P=0.02) of peak effort was observed. No significant differences were observed in arterial blood pressure, oxygen consumption at submaximal and maximal effort, exercise duration, respiratory ratio, CO2 production, ventilation threshold, minute ventilation, and oxygen pulse. CONCLUSION: Pyridostigmine, at a dose of 45mg, decreases heart rate at rest and during exercise, with minimal side effects and without interfering with exercise tolerance and ventilation variables.

Avaliando a atividade vagal cardíaca na eletrocardiografia convencional

OBJETIVO: Determinar a viabilidade da utilização de traçado convencional de eletrocardiografia (ECG) para avaliação da atividade vagal cardíaca (AVC). MÉTODOS: Foram analisados, retrospectivamente, 1.395 indivíduos (995 homens), na faixa de idade de 46 + 17,2 anos (média ± desvio padrão), com traçados de ECG convencional para medida do Delta RR, que representa a diferença, em ms, entre o maior e o menor intervalo RR, e com resultados da avaliação autonômica parassimpática, o teste de exercício de quatro segundos (T4s), que quantifica a AVC por meio do índice vagal cardíaco (IVC). Foram obtidas curvas ROC para determinar os valores de Delta RR com melhor relação entre sensibilidade e especificidade para os pontos de corte de baixa e alta AVC, respectivamente, de 1,20 e 1,95. RESULTADOS: Os valores de delta RR correlacionaram-se significativamente com os de IVC (r = 0,40; p < 0,001). Foram identificados < 60 ms e > 120 ms como os melhores pontos de corte para baixa e alta AVC, com sensibilidade de 75% e 57%, especificidade de 62% e 79% e áreas das curvas ROC de 0,76 e 0,74, respectivamente. CONCLUSÃO: A medida visual do delta RR em um traçado de ECG parece ser válida para a avaliação clínica preliminar e rápida da AVC, podendo ser útil em consultórios, emergências ou situações nas quais o uso de métodos mais sofisticados de avaliação autonômica não seja viável, oportuno ou conveniente.

Normotensos com resposta pressórica exagerada ao exercício possuem tônus vagal cardíaco aumentado

FUNDAMENTO: Valores exagerados da pressão arterial sistólica (PAS) durante um teste cardiopulmonar de exercício máximo (TCPE) são classicamente considerados como inapropriados e associados a um maior risco para desenvolvimento de doenças cardiovasculares. Sabe-se que o sistema nervoso autônomo modula a PA no exercício. Contudo, não está claramente estabelecido o comportamento do tônus vagal cardíaco (TVC) em indivíduos saudáveis com uma resposta pressórica exagerada no TCPE. OBJETIVO: Analisar o comportamento do TVC em homens adultos saudáveis que apresentam uma resposta pressórica exagerada no TCPE. MÉTODOS: De 2.505 casos avaliados entre 2002-2009, foram identificados criteriosamente 154 casos de homens, entre 20-50 anos de idade, saudáveis e normotensos. A avaliação incluía exame clínico, medidas antropométricas, testes de exercício de 4 segundos (tônus vagal cardíaco) e TCPE realizado em cicloergômetro, com medidas de pressão arterial a cada minuto pelo método auscultatório. Baseado no valor máximo de PAS obtido no TCPE, a amostra foi dividida em tercis, comparando-se o TVC, a carga máxima e o VO2 máximo. RESULTADOS: Os valores de TVC diferiram entre os indivíduos que se apresentavam nos tercis inferior e superior para a resposta da PAS ao TCPE, respectivamente, 1,57 ± 0,03 e 1,65 ± 0,04 (média ± erro padrão da média) (p = 0,014). Os dois tercis também diferiam quanto ao VO2 máximo (40,7 ± 1,3 vs 46,4 ± 1,3 ml/kg-1.min-1; p = 0,013) e a carga máxima (206 ± 6,3 vs 275 ± 8,7 watts; p < 0,001). CONCLUSÃO: Uma resposta pressórica exagerada durante o TCPE em homens adultos saudáveis é acompanhada de indicadores de bom prognóstico clínico, incluindo níveis mais altos de condição aeróbica e de tônus vagal cardíaco.

Comparação entre métodos de avaliação da modulação vagal cardíaca

FUNDAMENTO: Diversos métodos têm sido utilizados para avaliar a modulação vagal cardíaca; entretanto, há lacunas quanto a associação e acurácia desses métodos. OBJETIVO: Investigar a associação entre três métodos válidos, reprodutíveis e comumente utilizados para avaliação da modulação vagal cardíaca, e comparar as suas acurácias. MÉTODOS: Trinta homens saudáveis (23 ± 4 anos) e 15 homens com coronariopatia (61 ± 10 anos) foram avaliados em ordem contrabalanceada pela Variabilidade da Frequência Cardíaca (VFC; variáveis: domínio do tempo = pNN50, DPNN e RMSSD, domínio da frequência = AF ms² e AF u.n.), Arritmia Sinusal Respiratória (ASR) e Teste de Exercício de 4 segundos (T4s). RESULTADOS: Indivíduos saudáveis apresentaram maior modulação vagal nos três métodos (p < 0,05). No grupo saudável houve correlação (p < 0,05) entre os resultados da VFC (pNN50 e DPNN) e da ASR, mas não houve correlação entre o T4s e os outros dois métodos estudados. No grupo com coronariopatia houve correlação entre os resultados da VFC (pNN50, DPNN, RMSSD, AF ms² e AF u.n.) e da ASR. Em adição, houve correlação entre o T4s e a ASR. Por fim, os métodos ASR e T4s apresentaram tamanho do efeito mais preciso e melhor acurácia (p < 0,05) comparados à VFC. CONCLUSÃO: A VFC e a ASR geraram resultados parcialmente redundantes em indivíduos saudáveis e em pacientes com coronariopatia, enquanto o T4s gerou resultados complementares a VFC e ASR em indivíduos saudáveis. Além disso, os métodos ASR e T4s foram mais precisos para discriminar a modulação vagal cardíaca entre indivíduos saudáveis e pacientes com coronariopatia comparados à VFC.

Changes induced in Biomphalaria glabrata (Say, 1818) following trials for artificial stimulation of its internal defense system

Biomphalaria glabrata can react through different pathways to Schistosoma mansoni miracidium penetration, according to the degree of resistance/susceptibility presented by different snail strains, which is a genetically determined character, resistance being the dominant feature. However, it has been observed that previous susceptible snail strain may change its reactive behavior along the course of infection, exhibiting later a pattern of cercarial shedding and histopatopathological picture compatible with high resistance. Such observation suggests the possibility of B. glabrata to develop a sort of adaptative immunity face a schistosome infection. To explore on this aspect, the present investigation looked for the behavior of S. mansoni infection in B. glabrata previously subjected to different means of artificial stimulation of its internal defense system. Snails previously inoculated with irradiated miracídia (Group I); treated with S. mansoni antigens (Group II) or with a non-related parasite antigen (Group III) were challenged with 20 viable S. mansoni miracidia, and later looked for cercarial shedding and histopathologic changes at different times from exposition. Nodules of hemocyte accumulations were found at the site of antigen injection. These nodules resembled solid granulomas, and were larger and more frequent in snails injected with S. mansoni products as compared to those injected with Capillaria hepatica. However, the presence of such granulomas did not avoid the S. mansoni challenge infection from developing in a similar way as that seen in controls. The data are indicative that hemocytes are able to proliferate locally when stimulated, such capacity also remaining localized, not being shared by the population of hemocytes located elsewhere within the snail body.

Sympathetic glial cells and macrophages develop different responses to Trypanosoma cruzi infection or lipopolysaccharide stimulation

Nitric oxide (NO) participates in neuronal lesions in the digestive form of Chagas disease and the proximity of parasitised glial cells and neurons in damaged myenteric ganglia is a frequent finding. Glial cells have crucial roles in many neuropathological situations and are potential sources of NO. Here, we investigate peripheral glial cell response to Trypanosoma cruzi infection to clarify the role of these cells in the neuronal lesion pathogenesis of Chagas disease. We used primary glial cell cultures from superior cervical ganglion to investigate cell activation and NO production after T. cruzi infection or lipopolysaccharide (LPS) exposure in comparison to peritoneal macrophages. T. cruzi infection was greater in glial cells, despite similar levels of NO production in both cell types. Glial cells responded similarly to T. cruzi and LPS, but were less responsive to LPS than macrophages were. Our observations contribute to the understanding of Chagas disease pathogenesis, as based on the high susceptibility of autonomic glial cells to T. cruzi infection with subsequent NO production. Moreover, our findings will facilitate future research into the immune responses and activation mechanisms of peripheral glial cells, which are important for understanding the paradoxical responses of this cell type in neuronal lesions and neuroprotection.