End-systolic pressure-diameter relation of the left ventricle during transient and sustained elevations of blood pressure

OBJECTIVE: To assess the effect of transient and sustained variations in cardiac load on the values of the end-systolic pressure-diameter relation (ESPDR) of the left ventricle. METHODS: We studied 13 dogs under general anesthesia and autonomic blockade. Variations of cardiac loads were done by elevation of blood pressure by mechanical constriction of the aorta. Two protocols were used in each animal: gradual peaking and decreasing pressure variation, the "transient arterial hypertension protocol" (TAH), and a quick and 10 min sustained elevation, the "sustained arterial hypertension protocol"(SAH). Then, we compared the ESDR in these two situations. RESULTS: Acute elevation of arterial pressure, being it "transitory" or "sustained", did not alter the heart frequency and increased similarly the preload and after load. However, they acted differently in end systolic pressure-diameter relation. It was greater in the SAH than TAH protocol, 21.0±7.3mmHg/mm vs. 9.2±1.2mmHg/mm (p<0.05). CONCLUSION: The left ventricular ESPDR values determined during sustained pressure elevations were higher than those found during transient pressure elevations. The time-dependent activation of myocardial contractility associated with the Frank-Starling mechanism is the major factor in inotropic stimulation during sustained elevations of blood pressure, determining an increase in the ESPDR values.

Reduction of QTc interval dispersion. Potential mechanism of cardiac protection of pyridostigmine bromide

OBJECTIVE: Parasympathetic dysfunction is an independent risk factor in individuals with coronary artery disease, and cholinergic stimulation is a potential therapeutical option. We determined the effects of pyridostigmine bromide, a reversible anticholinesterase agent, on electrocardiographic variables of healthy individuals. METHODS: We carried out a cross-sectional, double blind, randomized, placebo-controlled study. We obtained electrocardiographic tracings in 12 simultaneous leads of 10 healthy young individuals at rest before and after oral administration of 45 mg of pyridostigmine or placebo. RESULTS: Pyridostigmine increased RR intervals (before: 886±27 ms vs after: 1054±37 ms) and decreased QTc dispersion (before: 72±9ms vs after: 45±3ms), without changing other electrocardiographic variables (PR segment, QT interval, QTc, and QT dispersion). CONCLUSION: Bradycardia and the reduction in QTc dispersion induced by pyridostigmine may effectively represent a protective mechanism if these results can be reproduced in individuals with cardiovascular diseases.

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.

Sex differences in the fetal heart rate variability indices of twins

Aims: To evaluate the differences in linear and complex heart rate dynamics in twin pairs according to fetal sex combination [male-female (MF), male-male (MM), and female-female (FF)]. Methods: Fourteen twin pairs (6 MF, 3 MM, and 5 FF) were monitored between 31 and 36.4 weeks of gestation. Twenty-six fetal heart rate (FHR) recordings of both twins were simultaneously acquired and analyzed with a system for computerized analysis of cardiotocograms. Linear and nonlinear FHR indices were calculated. Results: Overall, MM twins presented higher intrapair average in linear indices than the other pairs, whereas FF twins showed higher sympathetic-vagal balance. MF twins exhibited higher intrapair average in entropy indices and MM twins presented lower entropy values than FF twins considering the (automatically selected) threshold rLu. MM twin pairs showed higher intrapair differences in linear heart rate indices than MF and FF twins, whereas FF twins exhibited lower intrapair differences in entropy indices. Conclusions: The results of this exploratory study suggest that twins have sex-specific differences in linear and nonlinear indices of FHR. MM twins expressed signs of a more active autonomic nervous system and MF twins showed the most active complexity control system. These results suggest that fetal sex combination should be taken into consideration when performing detailed evaluation of the FHR in twins.

Prenatal dopamine and neonatal behavior and biochemistry

Depressed pregnant women (N=126) were divided into high and low prenatal maternal dopamine (HVA) groups based on a tertile split on their dopamine levels at 20 weeks gestation. The high versus the low dopamine group had lower Center for Epidemiological Studies-Depression Scale (CES-D) scores, higher norepinephrine levels at the 20-week gestational age visit and higher dopamine and serotonin levels at both the 20- and the 32-week gestational age visits. The neonates of the mothers with high versus low prenatal dopamine levels also had higher dopamine and serotonin levels as well as lower cortisol levels. Finally, the neonates in the high dopamine group had better autonomic stability and excitability scores on the Brazelton Neonatal Behavior Assessment Scale. Thus, prenatal maternal dopamine levels appear to be negatively related to prenatal depression scores and positively related to neonatal dopamine and behavioral regulation, although these effects are confounded by elevated serotonin levels.

Contribuição para o estudo da fibromialgia : análise de variáveis de aptidão física, de composição corporal e capacidade funcional

A presente dissertação pretendeu verificar o efeito de um programa de exercício supervisionado versus domiciliário, de intensidade moderada, com a duração de 16 semanas, na aptidão física de pessoas com fibromialgia. Houve necessidade de ajustamento dos objetivos e analisaram-se os dados obtidos no primeiro momento de avaliação, pretendendo-se analisar a relação entre variáveis de aptidão física, contribuindo para a compreensão da aptidão física de pessoas com fibromialgia. Apresentam-se e analisam-se variáveis de aptidão física e os resultados do efeito do exercício a nível de composição corporal, capacidade cardiorrespiratória e capacidade funcional. Neste âmbito realizaram-se 5 estudos. No estudo I analisou-se a precisão de diferentes equações preditivas de consumo de oxigénio, que utilizam a distância caminhada no teste de marcha de 6 minutos e propõe-se uma atualização para a equação específica para esta população. No estudo II observou-se a relação entre o consumo de oxigénio, composição corporal e força muscular. No estudo III avaliou-se a precisão de equações preditivas de composição corporal utilizando pregas adiposas e a densitometria de raio-X de dupla energia como método de referência. No estudo IV verificou-se qual o índice que melhor reflete a composição corporal destas mulheres. No estudo V analisou-se a associação entre a frequência cardíaca de recuperação, após um teste de esforço máximo e o consumo de oxigénio. Os principais resultados reforçam os resultados anteriores de que a população estudada apresenta diminuição da aptidão física, da capacidade funcional e valores de composição corporal indicativos de excesso de peso. Não apresentaram alterações autonómicas e verificou-se que a distância caminhada durante o teste de marcha de 6 minutos, a idade, percentagem de massa gorda e a massa magra apendicular são preditores do VO2 pico. Após a intervenção as participantes apresentaram alterações positivas a nível da aptidão física.

Neuropatia autonômica cardiovascular diabética: fatores de risco, impacto clínico e diagnóstico precoce

A neuropatia autonômica cardiovascular (NAC) constitui uma das complicações de maior repercussão clínica do diabete melito (DM) e, ao mesmo tempo, está entre as menos diagnosticadas. Nesta revisão, são discutidos os principais fatores de risco para o desenvolvimento e a progressão da NAC nos pacientes com DM, a história natural da neuropatia autonômica e seu impacto na doença cardiovascular do DM, bem como os testes para o diagnóstico precoce e o estadiamento da NAC na prática clínica. A pesquisa bibliográfica teve como base dois bancos de dados: Medline e Tripdatabase, com os seguintes descritores: diabetic cardiovascular autonomic neuropathy e cardiovascular autonomic neuropathy and diabetes. Os artigos de 1998 a 2007 em inglês e alemão foram selecionados. A NAC em estágios iniciais (precoce e intermediária) pode ser diagnosticada e revertida, porém, nos casos avançados (estágio grave), resta apenas o tratamento sintomático. A NAC está associada a um maior índice de morbidade e mortalidade cardiovasculares e pior qualidade de vida nos indivíduos diabéticos

Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas Disease

Background:Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence.Objective:To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias.Method:Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram).Results:GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028).Conclusion:The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias.

Spectral Analysis Related to Bare-Metal and Drug-Eluting Coronary Stent Implantation

Background: The autonomic nervous system plays a central role in cardiovascular regulation; sympathetic activation occurs during myocardial ischemia. Objective: To assess the spectral analysis of heart rate variability during stent implantation, comparing the types of stent. Methods: This study assessed 61 patients (mean age, 64.0 years; 35 men) with ischemic heart disease and indication for stenting. Stent implantation was performed under Holter monitoring to record the spectral analysis of heart rate variability (Fourier transform), measuring the low-frequency (LF) and high-frequency (HF) components, and the LF/HF ratio before and during the procedure. Results: Bare-metal stent was implanted in 34 patients, while the others received drug-eluting stents. The right coronary artery was approached in 21 patients, the left anterior descending, in 28, and the circumflex, in 9. As compared with the pre-stenting period, all patients showed an increase in LF and HF during stent implantation (658 versus 185 ms2, p = 0.00; 322 versus 121, p = 0.00, respectively), with no change in LF/HF. During stent implantation, LF was 864 ms2 in patients with bare-metal stents, and 398 ms2 in those with drug-eluting stents (p = 0.00). The spectral analysis of heart rate variability showed no association with diabetes mellitus, family history, clinical presentation, beta-blockers, age, and vessel or its segment. Conclusions: Stent implantation resulted in concomitant sympathetic and vagal activations. Diabetes mellitus, use of beta-blockers, and the vessel approached showed no influence on the spectral analysis of heart rate variability. Sympathetic activation was lower during the implantation of drug-eluting stents.

Proposal Intensity Adequacy of Expiratory Effort and Heart Rate Behavior During the Valsalva Maneuver in Preadolescents

Background: When performing the Valsalva maneuver (VM), adults and preadolescents produce the same expiratory resistance values. Objective: To analyze heart rate (HR) in preadolescents performing VM, and propose a new method for selecting expiratory resistance. Method: The maximal expiratory pressure (MEP) was measured in 45 sedentary children aged 9-12 years who subsequently performed VM for 20 s using an expiratory pressure of 60%, 70%, or 80% of MEP. HR was measured before, during, and after VM. These procedures were repeated 30 days later, and the data collected in the sessions (E1, E2) were analyzed and compared in periods before, during (0-10 and 10-20 s), and after VM using nonparametric tests. Results: All 45 participants adequately performed VM in E1 and E2 at 60% of MEP. However, only 38 (84.4%) and 25 (55.5%) of the participants performed the maneuver at 70% and 80% of MEP, respectively. The HR delta measured during 0-10 s and 10-20 s significantly increased as the expiratory effort increased, indicating an effective cardiac autonomic response during VM. However, our findings suggest the VM should not be performed at these intensities. Conclusion: HR increased with all effort intensities tested during VM. However, 60% of MEP was the only level of expiratory resistance that all participants could use to perform VM. Therefore, 60% of MEP may be the optimal expiratory resistance that should be used in clinical practice.

Effects of Exercise Training on Heart Rate Variability in Chagas Heart Disease

Background: Heart rate variability (HRV) is a marker of autonomic dysfunction severity. The effects of physical training on HRV indexes in Chagas heart disease (CHD) are not well established. Objective: To evaluate the changes in HRV indexes in response to physical training in CHD. Methods: Patients with CHD and left ventricular (LV) dysfunction, physically inactive, were randomized either to the intervention (IG, N = 18) or control group (CG, N = 19). The IG participated in a 12-week exercise program consisting of 3 sessions/week. Results: Mean age was 49.5 ± 8 years, 59% males, mean LVEF was 36.3 ± 7.8%. Baseline HRV indexes were similar between groups. From baseline to follow-up, total power (TP): 1653 (IQ 625 - 3418) to 2794 (1617 - 4452) ms, p = 0.02) and very low frequency power: 586 (290 - 1565) to 815 (610 - 1425) ms, p = 0.047) increased in the IG, but not in the CG. The delta (post - pre) HRV indexes were similar: SDNN 11.5 ± 30.0 vs. 3.7 ± 25.1 ms. p = 0.10; rMSSD 2 (6 - 17) vs. 1 (21 - 9) ms. p = 0.43; TP 943 (731 - 3130) vs. 1780 (921 - 2743) Hz. p = 0.46; low frequency power (LFP) 1.0 (150 - 197) vs. 60 (111 - 146) Hz. p = 0.85; except for high frequency power, which tended to increase in the IG: 42 (133 - 92) vs. 79 (61 - 328) Hz. p = 0.08). Conclusion: In the studied population, the variation of HRV indexes was similar between the active and inactive groups. Clinical improvement with physical activity seems to be independent from autonomic dysfunction markers in CHD.

Sleep Apnea and Nocturnal Cardiac Arrhythmia: A Populational Study

Background: The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea. Objective: To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample. Methods: Cross-sectional study with 1,101 volunteers, who form a representative sample of the city of São Paulo. The overnight polysomnography was performed using an EMBLA® S7000 digital system during the regular sleep schedule of the individual. The electrocardiogram channel was extracted, duplicated, and then analyzed using a Holter (Cardio Smart®) system. Results: A total of 767 participants (461 men) with a mean age of 42.00 ± 0.53 years, were included in the analysis. At least one type of nocturnal cardiac rhythm disturbance (atrial/ventricular arrhythmia or beat) was observed in 62.7% of the sample. The occurrence of nocturnal cardiac arrhythmias was more frequent with increased disease severity. Rhythm disturbance was observed in 53.3% of the sample without breathing sleep disorders, whereas 92.3% of patients with severe obstructive sleep apnea showed cardiac arrhythmia. Isolated atrial and ventricular ectopy was more frequent in patients with moderate/severe obstructive sleep apnea when compared to controls (p < 0.001). After controlling for potential confounding factors, age, sex and apnea-hypopnea index were associated with nocturnal cardiac arrhythmia. Conclusion: Nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea and the prevalence increases with disease severity. Age, sex, and the Apnea-hypopnea index were predictors of arrhythmia in this sample.

4-Second Exercise Test: Reference Values for Ages 18–81 Years

Background: Physiological reflexes modulated primarily by the vagus nerve allow the heart to decelerate and accelerate rapidly after a deep inspiration followed by rapid movement of the limbs. This is the physiological and pharmacologically validated basis for the 4-s exercise test (4sET) used to assess the vagal modulation of cardiac chronotropism. Objective: To present reference data for 4sET in healthy adults. Methods: After applying strict clinical inclusion/exclusion criteria, 1,605 healthy adults (61% men) aged between 18 and 81 years subjected to 4sET were evaluated between 1994 and 2014. Using 4sET, the cardiac vagal index (CVI) was obtained by calculating the ratio between the duration of two RR intervals in the electrocardiogram: 1) after a 4-s rapid and deep breath and immediately before pedaling and 2) at the end of a rapid and resistance-free 4-s pedaling exercise. Results: CVI varied inversely with age (r = -0.33, p < 0.01), and the intercepts and slopes of the linear regressions between CVI and age were similar for men and women (p > 0.05). Considering the heteroscedasticity and the asymmetry of the distribution of the CVI values according to age, we chose to express the reference values in percentiles for eight age groups (years): 18–30, 31–40, 41–45, 46–50, 51–55, 56–60, 61–65, and 66+, obtaining progressively lower median CVI values ranging from 1.63 to 1.24. Conclusion: The availability of CVI percentiles for different age groups should promote the clinical use of 4sET, which is a simple and safe procedure for the evaluation of vagal modulation of cardiac chronotropism.

Heart Rate Variability Correlates to Functional Aerobic Impairment in Hemodialysis Patients

Background:Autonomic dysfunction (AD) is highly prevalent in hemodialysis (HD) patients and has been implicated in their increased risk of cardiovascular mortality.Objective:To correlate heart rate variability (HRV) during exercise treadmill test (ETT) with the values obtained when measuring functional aerobic impairment (FAI) in HD patients and controls.Methods:Cross-sectional study involving HD patients and a control group. Clinical examination, blood sampling, transthoracic echocardiogram, 24-hour Holter, and ETT were performed. A symptom-limited ramp treadmill protocol with active recovery was employed. Heart rate variability was evaluated in time domain at exercise and recovery periods.Results:Forty-one HD patients and 41 controls concluded the study. HD patients had higher FAI and lower HRV than controls (p<0.001 for both). A correlation was found between exercise HRV (SDNN) and FAI in both groups. This association was independent of age, sex, smoking, body mass index, diabetes, and clonidine or beta-blocker use, but not of hemoglobin levels.Conclusion:No association was found between FAI and HRV on 24-hour Holter or at the recovery period of ETT. Of note, exercise HRV was inversely correlated with FAI in HD patients and controls. (Arq Bras Cardiol. 2015; [online]. ahead print, PP.0-0)

Heart Rate and Systolic Blood Pressure Variability on Recently Diagnosed Diabetics

Background:Diabetes affects approximately 250 million people in the world. Cardiovascular autonomic neuropathy is a common complication of diabetes that leads to severe postural hypotension, exercise intolerance, and increased incidence of silent myocardial infarction.Objective:To determine the variability of heart rate (HR) and systolic blood pressure (SBP) in recently diagnosed diabetic patients.Methods:The study included 30 patients with a diagnosis of type 2 diabetes of less than 2 years and 30 healthy controls. We used a Finapres® device to measure during five minutes beat-to-beat HR and blood pressure in three experimental conditions: supine position, standing position, and rhythmic breathing at 0.1 Hz. The results were analyzed in the time and frequency domains.Results:In the HR analysis, statistically significant differences were found in the time domain, specifically on short-term values such as standard deviation of NN intervals (SDNN), root mean square of successive differences (RMSSD), and number of pairs of successive NNs that differ by more than 50 ms (pNN50). In the BP analysis, there were no significant differences, but there was a sympathetic dominance in all three conditions. The baroreflex sensitivity (BRS) decreased in patients with early diabetes compared with healthy subjects during the standing maneuver.Conclusions:There is a decrease in HR variability in patients with early type 2 diabetes. No changes were observed in the BP analysis in the supine position, but there were changes in BRS with the standing maneuver, probably due to sympathetic hyperactivity.