Effects of altering pedal frequency on the slow component of pulmonary VO2 kinetics and EMG activity.

This study investigated the effects of pedal frequency on the slow component of pulmonary oxygen uptake ( V O(2)) kinetics during heavy exercise at the same relative intensity. We hypothesized that higher pedal frequency (expected to enhance fast-twitch muscle fiber recruitment) would be associated with greater slow component amplitude (A' (s)), surface electromyography (normalized root mean square; RMS) and blood lactate concentration ([lactate]). Eight subjects performed square-wave transitions to heavy exercise at 35 and 115 rpm. Furthermore, alternated cadences square-wave transitions (35-115 rpm) were performed to examine the potential effects of additional fast-twitch muscle fiber recruitment on the slow component. Significance was accepted when P<0.05. The A' (s) was greater at higher cadences (0.58+/-0.08 and 0.70+/-0.09 L.min (-1) at 115 and 35-115 rpm, respectively) than at 35 rpm (0.35+/-0.04 L.min (-1)). Greater EMG increase over time (DeltaRMS ((10-3 min))) and [lactate] were observed at 115 and 35-115 rpm compared with 35 rpm. There was a significant correlation between A' (s) and overall DeltaRMS ((10-3 min)) for all pedal frequencies combined (r=0.63; P=0.001). Pedal frequency had no effect on time constants or time delays. These findings are consistent with the concept that progressive recruitment of muscle fibers is associated with the V O(2) slow component.

Acute water ingestion increases arterial blood pressure in hypertensive and normotensive subjects.

In patients with severe autonomic dysfunction, water ingestion elicits an acute pressor response. Hypertension may be associated with changes in cardiovascular autonomic modulation, but there is no information on the acute effects of water ingestion in patients with hypertension. In this study, we compared the effect of acute water ingestion on haemodynamic and autonomic responses of hypertensive and normotensive individuals. Eight patients with mild hypertension were compared to 10 normotensive individuals. After 30 min resting in the supine position all subjects ingested 500 ml of water. At baseline and after water ingestion, venous blood samples for plasma volume determination were collected, and electrocardiographic tracings, finger blood pressure, forearm blood flow and muscle sympathetic nerve activity (MSNA) were obtained. Water ingestion resulted in similar and minor reduction in plasma volume. Systolic and diastolic blood pressure increased in both hypertensive (mean+/-s.d.: 19/14+/-6/3 mm Hg) and normotensive subjects (17/14+/-6/3 mm Hg). There was an increase in forearm vascular resistance and in MSNA. Heart rate was reduced (hypertensive: 5+/-1 beats/min, normotensive: 5+/-6 beats/min) and the high-frequency component of heart rate and systolic blood pressure variability was increased. In hypertensive and normotensive individuals, acute water ingestion elicits a pressor response, an effect that is most likely determined by an increased vasoconstrictor sympathetic activity, and is counterbalanced by an increase in blood pressure and heart rate vagal modulation.

Relationship between cardiovascular dysfunction and hyperglycemia in streptozotocin-induced diabetes in rats

Streptozotocin (STZ)-induced diabetes in rats is characterized by cardiovascular dysfunction beginning 5 days after STZ injection, which may reflect functional or structural autonomic nervous system damage. We investigated cardiovascular and autonomic function, in rats weighing 166 ± 4 g, 5-7, 14, 30, 45, and 90 days after STZ injection (N = 24, 33, 27, 14, and 13, respectively). Arterial pressure (AP), mean AP (MAP) variability (standard deviation of the mean of MAP, SDMMAP), heart rate (HR), HR variability (standard deviation of the normal pulse intervals, SDNN), and root mean square of successive difference of pulse intervals (RMSSD) were measured. STZ induced increased glycemia in diabetic rats vs control rats. Diabetes reduced resting HR from 363 ± 12 to 332 ± 5 bpm (P < 0.05) 5 to 7 days after STZ and reduced MAP from 121 ± 2 to 104 ± 5 mmHg (P = 0.007) 14 days after STZ. HR and MAP variability were lower in diabetic vs control rats 30-45 days after STZ injection (RMSSD decreased from 5.6 ± 0.9 to 3.4 ± 0.4 ms, P = 0.04 and SDMMAP from 6.6 ± 0.6 to 4.2 ± 0.6 mmHg, P = 0.005). Glycemia was negatively correlated with resting AP and HR (r = -0.41 and -0.40, P < 0.001) and with SDNN and SDMMAP indices (r = -0.34 and -0.49, P < 0.01). Even though STZ-diabetic rats presented bradycardia and hypotension early in the course of diabetes, their autonomic function was reduced only 30-45 days after STZ injection and these changes were negatively correlated with plasma glucose, suggesting a metabolic origin.

Relationship between cardiovascular dysfunction and hyperglycemia in streptozotocin-induced diabetes in rats.

Streptozotocin (STZ)-induced diabetes in rats is characterized by cardiovascular dysfunction beginning 5 days after STZ injection, which may reflect functional or structural autonomic nervous system damage. We investigated cardiovascular and autonomic function, in rats weighing 166 +/- 4 g, 5-7, 14, 30, 45, and 90 days after STZ injection (N = 24, 33, 27, 14, and 13, respectively). Arterial pressure (AP), mean AP (MAP) variability (standard deviation of the mean of MAP, SDMMAP), heart rate (HR), HR variability (standard deviation of the normal pulse intervals, SDNN), and root mean square of successive difference of pulse intervals (RMSSD) were measured. STZ induced increased glycemia in diabetic rats vs control rats. Diabetes reduced resting HR from 363 +/- 12 to 332 +/- 5 bpm (P < 0.05) 5 to 7 days after STZ and reduced MAP from 121 +/- 2 to 104 +/- 5 mmHg (P = 0.007) 14 days after STZ. HR and MAP variability were lower in diabetic vs control rats 30-45 days after STZ injection (RMSSD decreased from 5.6 +/- 0.9 to 3.4 +/- 0.4 ms, P = 0.04 and SDMMAP from 6.6 +/- 0.6 to 4.2 +/- 0.6 mmHg, P = 0.005). Glycemia was negatively correlated with resting AP and HR (r = -0.41 and -0.40, P < 0.001) and with SDNN and SDMMAP indices (r = -0.34 and -0.49, P < 0.01). Even though STZ-diabetic rats presented bradycardia and hypotension early in the course of diabetes, their autonomic function was reduced only 30-45 days after STZ injection and these changes were negatively correlated with plasma glucose, suggesting a metabolic origin.

Contribution of nitric oxide to arterial pressure and heart rate variability in rats submitted to high-sodium intake.

The aim of this study was to determine the contribution of NO to arterial pressure and heart rate variability in normotensive rats subjected to high sodium intake. Arterial pressure, heart rate, and arterial pressure and heart rate variability, baroreflex sensitivity, and pressure responsiveness were measured in male Wistar rats treated for 6 weeks (control and high sodium [1%] intake groups), before and after acute NO synthesis blockade. After treatment, no changes were observed in arterial pressure or heart rate. Arterial pressure variability was increased after sodium intake; however, heart rate variability and baroreflex sensitivity were not modified in high-sodium rats. NO synthase blockade increased arterial pressure in both groups but was higher in the high-sodium group (from 110+/-5 to 162+/-1.5 mm Hg) compared with the control group (from 109+/-6.7 to 144+/-10 mm Hg). The increase in arterial pressure was accompanied by a decrease in heart rate (from 354+/-28 to 303+/-25 bpm in control rats and from 380+/-34 to 298+/-30 bpm in high-sodium rats). NO synthase blockade increased the tachycardic response to sodium nitroprusside in high-sodium rats. Arterial pressure variability, evaluated by a nonlinear method (3D return maps), showed a larger reduction in response to NO synthase inhibition in the high-sodium group (from 162+/-26 to 34.8+/-8.6 for general index of beat-to-beat blood pressure variability) than in the control group (from 58+/-9.6 to 36+/-4.7 for general index of beat-to-beat blood pressure variability). Heart rate variability, evaluated by the SD of the R-R intervals, was not changed in control rats but was increased by NO synthase inhibition in the high-sodium rats (from 9.5+/-0.2 to 21.9+/-1.7 milliseconds). These findings suggest an important role for increased NO production in adaptation to high-sodium intake. The increase in NO system sensitivity in high-sodium intake may contribute to changes in the autonomic nervous system regulating heart rate and, especially, arterial pressure variability.

Enhancement of heart rate variability by cholinergic stimulation with pyridostigmine in healthy subjects.

The purpose of this study was to determine the effect of the oral administration of pyridostigmine bromide on indices of heart rate variability (HRV) in healthy young volunteers. Seventeen healthy participants (11 men, 6 women; aged 27 +/- 8 y) submitted to a randomized, crossover, double-blind protocol, in which they received 30 mg pyridostigmine bromide (PYR) or placebo orally at 8-hour intervals for 24 hours, on two separate days. Venous blood samples were collected 2 and 24 hours after the first dose for determination of serum cholinesterase activity. Holter tapes were recorded during the 24-hour period and analyzed using a semiautomatic technique to evaluate time- and frequency-domain indices of HRV and to build three-dimensional return maps for later quantification. Symptoms were mild and occurred similarly during administration of PYR and placebo (p = 0.140). Serum cholinesterase activity was reduced by 15% at 2 hours (p = 0.013) and by 14% at 24 hours (p = 0.010) after the first dose of PYR, but not after administration of placebo. Pyridostigmine administration caused a significant increase in the mean 24-hour R-R interval (placebo: 814 +/- 20 msec; PYR: 844 +/- 18 msec; p = 0.003) and in time-domain indices of HRV, such as the standard deviation of all R-R intervals (SDNN; placebo: 151 +/- 9 msec; PYR: 164 +/- 9 msec; p = 0.017), and the percentage of pairs of adjacent R-R intervals differing by more than 50 msec (pNN50; placebo: 12.8 +/- 1.8%; PYR: 13.9 +/- 1.5%; p = 0.029). Pyridostigmine had no significant effect on frequency-domain indices of HRV, but resulted in significant increase in P2, a parasympathetic index derived from the three-dimensional return map (placebo: 93 +/- 13 msec; PYR: 98 +/- 13 ms; p = 0.029). In conclusion, low-dose pyridostigmine reduced mean heart rate and increased HRV during a 24-hour period in healthy young subjects.

Parasympathetic dysautonomia precedes left ventricular systolic dysfunction in Chagas disease.

BACKGROUND: Parasympathetic dysautonomia is an established feature of advanced Chagas cardiomyopathy. However, in the absence of cardiac involvement, the presence of vagal dysfunction remains controversial. In a cross-sectional study, we compared patients with Chagas disease without cardiac involvement and healthy individuals by three different methods to determine whether vagal dysfunction is present in the early phase of Chagas disease. METHODS: Sixty-one patients with Chagas disease without cardiac involvement and 38 controls were submitted to respiratory sinus arrhythmia test and 24-hour Holter monitoring. Vagal heart influences were assessed by the expiratory/inspiratory (E/I) ratio, time-domain indexes of heart rate variability (HRV), and by the quantification of a 3-dimensional return map. RESULTS: The two groups were comparable in terms of left ventricular ejection fraction and left ventricular end-diastolic dimension. Compared with the control group, patients with Chagas disease had significantly lower values of the E/I ratio (mean +/- SD: 1.38 +/- 0.02 and 1.25 +/- 0.02, P <.004) and short-term indexes of HRV (median [interquartile range]-rMSSD: 23 [18-27] and 17 [13-23], P =.00; pNN50: 11 [7-17] and 6 [2-12], P =.00). P(3), a beat-to-beat HRV index derived from the 3-dimensional return map, also was significantly reduced in the Chagas disease group (mean +/- SD: 118 +/- 5 vs 100 +/- 4, P =.00). None of these indexes of vagal heart control were significantly correlated with left ventricular function or to the presence of esophageal radiologic abnormalities. CONCLUSION: Parasympathetic dysautonomia is an independent and early phenomenon in Chagas disease and may precede left ventricular systolic dysfunction.

Three-dimensional return map: a new tool for quantification of heart rate variability.

BACKGROUND: Several methods are used to study heart rate variability, but they have limitations, which might be overcome by the use of a three-dimensional return map. OBJECTIVES: To evaluate the performance of three-dimensional return map-derived indices to detect (1) sympathetic and parasympathetic modulation to the sinus node and (2) autonomic dysfunction in diabetic patients. METHODS: Six healthy subjects underwent partial and total pharmacological autonomic blockade in a protocol that incorporated vagal and sympathetic predominance. Twenty-two patients with type 2 diabetes mellitus and 12 normal controls participated in the subsequent validation experiment. Three-dimensional return maps were constructed by plotting RRn intervals versus the difference between adjacent RR intervals [(RRn+1)-(RRn)] versus the number of counts, and four derived indices (P1, P2, P3, MN) were created for quantification. RESULTS: Both indices P1 and MN were significantly increased after sympathetic blockade with propranolol, while all indices except P1 were modified after parasympathetic blockade (P < 0.05). During the validation experiments, P1 and MN detected differences between normal controls, and diabetic patients with and without autonomic neuropathy. The overall accuracy of most three-dimensional indices to detect autonomic dysfunction, estimated by the area under the ROC curve, was significantly better than traditional time domain indices. Three-dimensional return map-derived indices also showed adequate reproducibility on two different recording days (intra-class correlation coefficients of 0.69 to 0.82; P < 0.001). CONCLUSIONS: Three-dimensional return map-derived indices are reproducible, quantify parasympathetic as well as sympathetic modulation to the sinus node, and are capable of detecting autonomic dysfunction in diabetic patients.

Atrial automaticity and atrioventricular conduction in athletes: contribution of autonomic regulation.

Little is known about the sinoatrial automatism and atrioventricular conduction of trained individuals who present a normal resting electrocardiogram. We used transesophageal atrial stimulation, a minimally invasive technique, to evaluate aerobically trained athletes (n = 10) and sedentary individuals (n = 10) with normal resting electrocardiograms, to test the hypothesis that parasympathetic tone, as detected by heart rate variability, could be associated with changes in sinoatrial automatism and atrioventricular conduction. Corrected sinus node recovery time tended to be longer in athletes than in sedentary individuals, but this difference did not reach statistical significance. The Wenckebach point occurred at a lower rate in athletes than in the controls. Over a 24-h period of measurement, the mean RR interval was longer in the athletes than in the sedentary individuals. The mean square root of successive differences (rMSSD) tended to be higher in athletes than in controls, but this difference did not reach statistical significance. There was a moderate correlation (r = 0.48, P < 0.05) between the index of atrioventricular conduction, the rate at the Wenckebach point, and the logarithmically transformed rMSSD. Thus, as a corollary to its effects on the sinus node, where increased parasympathetic tone, decreased sympathetic tone, and non-autonomic components may contribute to sinus bradycardia, it is possible that athletic training may also induce intrinsic adaptations in the conduction system, which could contribute to the higher prevalence of atrioventricular conduction abnormalities observed in athletes.

Autonomic dysfunction and urinary albumin excretion rate are associated with an abnormal blood pressure pattern in normotensive normoalbuminuric type 1 diabetic patients.

OBJECTIVE: To analyze the role of autonomic function and other possible factors associated with a blunted fall in nocturnal blood pressure. RESEARCH DESIGN AND METHODS: A total of 39 normotensive normnoalbuminuric type 1 diabetic patients were studied. Glomerular filtration rate (51Cr-EDTA technique), extracellular volume (51Cr-EDTA distribution volume), and urinary albumin excretion rate (UAER) (by radioimmunoassay) were measured. The subjects' 24-h ambulatory blood pressure and a 24-h electrocardiogram were recorded simultaneously Heart rate variability was calculated in the time domain for 24 h, in the frequency domain at night, at rest in the supine position, and during tilt. Patients were classified according to diastolic blood pressure (dBP) night/day ratio as dipper patients (< or =0.9) and nondipper patients (>0.9). RESULTS: Nondipper patients presented a higher low-frequency (LF) component (a sympathetic index) and higher LF/high-frequency (HF) ratio during sleep than dipper patients (0.29 +/- 0.12 vs. 0.19 +/- 0.10 normalized units [n.u.], P = 0.008; and 0.98 +/- 0.53 vs. 0.55 +/- 0.45 n.u., P = 0.007, respectively). At rest, the LF component in nondipper patients (0.38 +/- 0.13 n.u.) was higher than in dipper patients (0.27 +/- 0.12 n.u., P = 0.04). After the tilt, nondipper patients did not show an increase in the LF component (P = 0.32), but in dipper patients, the increase was significant (P = 0.001). In both groups, tilting promoted a decrease in the HF component (a parasympathetic index). In a stepwise multiple linear regression analysis, the LF component during sleep and the UAER accounted for 24% of the variability in the dBP night/day ratio. CONCLUSIONS: The predominance of sympathetic activity and increased levels of UAER, although within the normal range, are associated with a blunted fall in nocturnal dBP in normoalbuminuric normotensive type 1 diabetic patients.

Novo equipamento desenvolvido no HCPA para cirurgia otológica (microcautério). Parte II - Estudo em seres humanos / New equipment for otologic surgery developed at HCPA (microcautery). Parte II -Study in human beings

Objetivo: Descrever a avaliação em cirurgias do ouvido médio em seres humanos, do microcautério otológico Lavinsky/HCPA...

Effect of partial arrhythmia suppression with amiodarone on heart rate variability of patients with congestive heart failure.

BACKGROUND: Some antiarrythmic agents that may increase mortality rates have been shown to reduce heart rate variability in patients with heart failure. Amiodarone is a potent antiarrhythmic agent that may reduce mortality rates in heart failure, but little is known about its effects on heart rate variability. METHODS AND RESULTS: The purpose of this study was to evaluate the effect of partial arrhythmia suppression by amiodarone on indexes of heart rate variability in patients with heart failure. Ten clinically stable patients in New York Heart Association class II-III received amiodarone during a 4-week period (600 mg every day for 14 days and 300 mg every day for 16 days), and 24-hour Holter recordings were performed before and after treatment. Heart rate variability indexes were calculated by a semiautomatic method that applies a 20% filter to the temporal series, excluding ectopy and compensatory pauses. After amiodarone administration, there was a significant reduction in pNN50 from 8% +/- 7% to 3% +/- 2% (p < 0.05) and there was a trend toward reduction in rMSSD (p = 0.06). Other time domain indexes did not change significantly. Spectral analysis demonstrated a significant reduction of low-frequency components (421 +/- 122 to 151 +/- 25 msec2; p < 0.05) and total power (1503 +/- 314 to 609 +/- 144 msec2, p < 0.05). Multivariate analysis showed that the observed reduction in pNN50 was strongly associated with the number and the reduction of ventricular premature contractions before and after amiodarone administration (r2 = 0.94; p < 0.01). CONCLUSIONS: These findings indicate that despite the use of software corrections for arrhythmia, short-term time domain indexes of heart rate variability may be affected by partial suppression of ectopy.

Sympathetic nervous system representation in time and frequency domain indices of heart rate variability.

This study evaluated the contributions of sympathetic and parasympathetic modulation to heart rate variability during situations in which vagal and sympathetic tone predominated. In a placebo-controlled, randomized, double blind blockade study, six young healthy male individuals received propranolol (0.2 mg x kg(-1)), atropine (0.04 mg x kg(-1)), propranolol plus atropine, or placebo infusions over 4 days. Time-domain indices were calculated during 40 min of rest and 20 min of exercise at 70% of maximal exercise intensity. Spectrum analysis, using fast Fourier transformation, was also performed at rest and during the exercise. The time-domain indices standard deviation of R-R intervals, mean of the standard deviations of all R-R intervals for all 5-min segments, percentage of number of pairs of adjacent R-R intervals differing by more than 50 ms, and square root of the mean of the sum of squares of differences between adjacent R-R intervals were reduced after atropine and propranolol plus atropine. Propranolol alone caused no appreciable change in any of the time-domain indices. At rest, all spectrum components were similar after placebo and propranolol infusions, but following parasympathetic and double autonomic blockade there was a reduction in all components of the spectrum analysis, except for the low:high ratio. During exercise, partial and double blockade did not change significantly any of the spectrum components. Thus, time and frequency-domain indices of heart rate variability were able to detect vagal activity, but could not detect sympathetic activity. During exercise, spectrum analysis is not capable of evaluating autonomic modulation of heart rate.

Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin

Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP) variability) in rats (164.5 + 1.7 g) 7, 14, 30 and 120 days after streptozotocin (STZ) injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN) and root mean square of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN) derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn+1) - (MAPn)] x density. The indices represent the maximum concentration of points (P1), the longitudinal axis (P2), and the transversal axis (P3) and MN represents P1 x P2 x P3 x 10(-3), STZ induced increased urinary glucose in diabetic (D) rats compared to controls (C). Seven days after STZ, diabetes reduced resting HR from 380.6 + 12.9 to 319,2 + 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 + 1.67 to 19.87 + 2.60 ms, did not change MAP, and reduced P1 from 61.0 + 5.3 to 51.5 + 1.8 arbitrary units (AU), P2 from 41.3 + 0.3 to 29.0 + 1.8 AU, and MN from 171.1. + 30.2 to 77.2 + 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r=-0.76, P=0.03) as well as with the MN index (r=-0.83, P=0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The metabolic control may influence the results, suggesting that insulin treatment and a better metabolic control in this model may modify arterial pressure, HR and MAP variability.

Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin.

Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP) variability) in rats (164.5 +/- 1.7 g) 7, 14, 30 and 120 days after streptozotocin (STZ) injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN) and root mean square of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN) derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn + 1)-(MAPn)] x density. The indices represent the maximum concentration of points (P1), the longitudinal axis (P2), and the transversal axis (P3) and MN represents P1 x P2 x P3 x 10(-3). STZ induced increased urinary glucose in diabetic (D) rats compared to controls (C). Seven days after STZ, diabetes reduced resting HR from 380.6 +/- 12.9 to 319.2 +/- 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 +/- 1.67 to 19.87 +/- 2.60 ms, did not change MAP, and reduced P1 from 61.0 +/- 5.3 to 51.5 +/- 1.8 arbitrary units (AU), P2 from 41.3 +/- 0.3 to 29.0 +/- 1.8 AU, and MN from 171.1 +/- 30.2 to 77.2 +/- 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r = -0.76, P = 0.03) as well as the MN index (r = -0.83, P = 0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The metabolic control may influence these results, suggesting that insulin treatment and a better metabolic control in this model may modify arterial pressure, HR and MAP variability.