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.

Acute Effects of Maternal Smoking on Fetal-Placental-Maternal System Hemodynamics

OBJECTIVE: To study acute hemodynamic alterations in the fetal-placental maternal system immediately after maternal exposure to nicotine. METHODS: This is a noncontrolled experimental study involving 21 pregnant smoking women, randomly selected, with uncomplicated pregnancies and without risk factors for fetal heart disease. Patients underwent ultrasound and fetal echocardiography before and after smoking a cigarette. They were asked to abstain from smoking for 12 hours before the study. The mean nicotine content of the cigarettes used in the study was 0.5mg of nicotine and 6mg of carbon monoxide. RESULTS: The average number of cigarettes smoked per a day prior to the study was 9.67. Gestational age ranged between 18 and 36 weeks. The mean maternal heart rate was elevated (P<0.001) as was the mean fetal heart rate (P=0.044). Maternal systolic blood pressure (P=0.004) and diastolic blood pressure (P=0.033) were also elevated after smoking. A decrease occurred in the systolic/diastolic ratio in the right uterine artery (P=0.014) and in the left uterine artery (P=0.039). The other hemodynamic variables remained unchanged. CONCLUSION: Cigarette smoking can cause changes in physiologic variables of fetal-placental circulation, but it does not change fetal cardiac function, in the dose of nicotine and its components used in this study. The decrease in systolic/diastolic ratio in the uterine arteries is probably related to a dose-dependent nicotine pattern.

Effects of Sibutramine on the Treatment of Obesity in Patients with Arterial Hypertension

OBJECTIVE: To assess the effects of weight reduction with 10mg of sibutramine or placebo on blood pressure during 24 hours (ambulatory blood pressure monitoring), on left ventricular mass, and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months. METHODS: The patients underwent echocardiography, ambulatory blood pressure monitoring, and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo. RESULTS: The group using sibutramine had a greater weight loss than that using placebo (6.7% versus 2.5%; p<0.001), an increase in heart rate (78.3±7.3 to 82±7.9 bpm; p=0.02), and a reduction in the left ventricular mass/height index (105±29.3 versus 96.6±28.58 g/m; p=0.002). Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy; blood pressure, however, did not change. CONCLUSION: The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy.

Electrocardiographic and Blood Pressure Alterations During Electroconvulsive Therapy in Young Adults

OBJECTIVE - To study cardiovascular alterations in young patients with no apparent organic disease who underwent electroconvulsive therapy. METHODS - The study comprised 47 healthy patients (22 males and 25 females) with a mean age of 30.3 years, who underwent electroconvulsive therapy. Ambulatory blood pressure monitoring and continuous electrocardiographic monitoring (Holter monitor) were performed during 24 hours. Blood pressure and heart rate were assessed 4 hours prior to electric shock administration, during electric shock administration, and 3 hours after electric shock administration. Arrhythmias and alterations in the ST segment in 24 hours were recorded. RESULTS - On electroconvulsive therapy, a significant increase in blood pressure and heart rate was observed and the measurements returned to basal values after 25 minutes. Three females had tracings with depression of the ST segment suggesting myocardial ischemia prior to and after electroconvulsive therapy. Coronary angiography was normal. No severe cardiac arrhythmias were diagnosed. CONCLUSION - 1) Electroconvulsive therapy is a safe therapeutic modality in psychiatry; 2) it causes a significant increase in blood pressure and heart rate; 3) it may be associated with myocardial ischemia in the absence of coronary obstructive disease; 4) electroconvulsive therapy was not associated with the occurrence of severe cardiac arrhythmias.

Metabolic and hemodynamic effects of saline infusion to maintain volemia on temporary abdominal aortic occlusion

OBJECTIVE: To analyze hemodynamic and metabolic effects of saline solution infusion in the maintenance of blood volume in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. METHODS: We studied 20 dogs divided into 2 groups: the ischemia-reperfusion group (IRG, n=10) and the ischemia-reperfusion group with saline solution infusion aiming at maintaining mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, n=10). All animals were anesthetized with sodium thiopental and maintained on spontaneous ventilation. Occlusion of the supraceliac aorta was obtained with inflation of a Fogarty catheter inserted through the femoral artery. After 60 minutes of ischemia, the balloon was deflated, and the animals were observed for another 60 minutes of reperfusion. RESULTS: IRG-SS dogs did not have hemodynamic instability after aortic unclamping, and the mean systemic blood pressure and heart rate were maintained. However, acidosis worsened, which was documented by a greater reduction of arterial pH that occurred especially due to the absence of a respiratory response to metabolic acidosis that was greater with the adoption of this procedure. CONCLUSION: Saline solution infusion to maintain blood volume avoided hemodynamic instability after aortic unclamping. This procedure, however, caused worsening in metabolic acidosis in this experimental model.

Mildly symptomatic chronic mitral regurgitation. Analysis of left ventricular systolic function and mitral regurgitant fraction under pharmacological influence: echocardiographic study

OBJECTIVE: To study echocardiographic parameters of left ventricular systolic function and valvar regurgitation under pharmacological influence in mildly symptomatic patients with chronic mitral regurgitation (MR). METHODS: We carried out a double-blind placebo controlled study in 12 patients with MR, mean aged 12.5 years old, who were randomized in 4 phases: A) digoxin; B) enalapril; C) digoxin + enalapril; D) placebo. The medication was administered for 30 days in each phase, and the following variables were analyzed: shortening and ejection fractions, wall stress index of left ventricle, left ventricular meridional end-systolic wall stress, Doppler-derived mean rate of left ventricular pressure rise (mean dP/dt), stroke volume and MR jet area. The clinical variables analysed were heart rate and systemic arterial pressure. RESULTS: No significant variation was observed in the clinical variables analysed. The shortening and ejection fraction, the mean dP/dt and stroke volume significantly increased and the wall stress index of left ventricle, the meridional left ventricular end systolic wall stress and the mitral regurgitation jet area decreased in the phases with medication as compared with that in the placebo phase. CONCLUSION: The parameters of left ventricular systolic function improved significantly and the degree of MR decreased with the isolated administration of digoxin or enalapril in mildly symptomatic patients with chronic MR. The combination of the drugs, however, did not show better results.

A new proposal to guide velocity and inclination in the ramp protocol for the treadmill ergometer

OBJECTIVE: To suggest criteria to guide protocol prescription in ramp treadmill testing, according to sex and age, based on velocity, inclination, and max VO2 reached by the population studied. METHODS: Prospective study describing heart rate (HR), time, velocity, inclination, and VO2 estimated at maximum effort of 1840 individuals from 4 to 79 years old, who performed a treadmill test (TT) according to the ramp protocol. A paired Student t test was used to assess the difference between predicted and reached max VO2, calculated according to the formulas of the "American College of Sports Medicine". RESULTS: Submaximal HR was surpassed in 90.1% of the examinations, with a mean time of 10.0±2.0 minute. Initial and peak inclination velocity of the exercise and max VO2 were inversely proportional to age and were greater in male patients. Predicted Max VO2 was significantly lower than that reached in all patients, except for female children and adolescents (age < 20 years old). CONCLUSION: Use of velocity, inclination, and maximum VO2 actually reached, as a criterion in prescribing the ramp protocol may help in the performance of exercise in treadmill testing. The ramp protocol was well accepted in all age groups and sexes with exercise time within the programmed 8 to 12 minutes.

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.

Hemodynamic Effect of Laser Therapy in Spontaneously Hypertensive Rats

Systemic arterial hypertension (SAH) is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world. The Low-Level Laser Therapy (LLLT), or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes. The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16) were randomly divided into the Laser Group (n = 8), which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8), which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group) and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group), revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group). Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats.

Obesity Preserves Myocardial Function During Blockade of the Glycolytic Pathway

Background: Obesity is defined by excessive accumulation of body fat relative to lean tissue. Studies during the last few years indicate that cardiac function in obese animals may be preserved, increased or diminished. Objective: Study the energy balance of the myocardium with the hypothesis that the increase in fatty acid oxidation and reduced glucose leads to cardiac dysfunction in obesity. Methods: 30-day-old male Wistar rats were fed standard and hypercaloric diet for 30 weeks. Cardiac function and morphology were assessed. In this paper was viewed the general characteristics and comorbities associated to obesity. The structure cardiac was determined by weights of the heart and left ventricle (LV). Myocardial function was evaluated by studying isolated papillary muscles from the LV, under the baseline condition and after inotropic and lusitropic maneuvers: myocardial stiffness; postrest contraction; increase in extracellular Ca2+ concentration; change in heart rate and inhibitor of glycolytic pathway. Results: Compared with control group, the obese rats had increased body fat and co-morbities associated with obesity. Functional assessment after blocking iodoacetate shows no difference in the linear regression of DT, however, the RT showed a statistically significant difference in behavior between the control and the obese group, most notable being the slope in group C. Conclusion: The energy imbalance on obesity did not cause cardiac dysfunction. On the contrary, the prioritization of fatty acids utilization provides protection to cardiac muscle during the inhibition of glycolysis, suggesting that this pathway is fewer used by obese cardiac muscle.

Hypotensive Response Magnitude and Duration in Hypertensives: Continuous and Interval Exercise

Background: Although exercise training is known to promote post-exercise hypotension, there is currently no consistent argument about the effects of manipulating its various components (intensity, duration, rest periods, types of exercise, training methods) on the magnitude and duration of hypotensive response. Objective: To compare the effect of continuous and interval exercises on hypotensive response magnitude and duration in hypertensive patients by using ambulatory blood pressure monitoring (ABPM). Methods: The sample consisted of 20 elderly hypertensives. Each participant underwent three ABPM sessions: one control ABPM, without exercise; one ABPM after continuous exercise; and one ABPM after interval exercise. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and double product (DP) were monitored to check post-exercise hypotension and for comparison between each ABPM. Results: ABPM after continuous exercise and after interval exercise showed post-exercise hypotension and a significant reduction (p < 0.05) in SBP, DBP, MAP and DP for 20 hours as compared with control ABPM. Comparing ABPM after continuous and ABPM after interval exercise, a significant reduction (p < 0.05) in SBP, DBP, MAP and DP was observed in the latter. Conclusion: Continuous and interval exercise trainings promote post-exercise hypotension with reduction in SBP, DBP, MAP and DP in the 20 hours following exercise. Interval exercise training causes greater post-exercise hypotension and lower cardiovascular overload as compared with continuous exercise.

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.

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

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