Michele Massaro

Effects of a residential exercise training on baroreflex sensitivity and heart rate variability in patients with coronary artery disease : A randomized, controlled study

Background—Myocardial ischemia and infarction impair baroreflex sensitivity (BRS), which when depressed is predictive of future cardiac events after myocardial infarction (MI). The main objective of this study was to determine whether exercise training improves BRS in patients with coronary artery disease. Methods and Results—Ninety-seven male patients with and without a previous MI were recruited after myocardial revascularization surgery and randomized into trained (TR) or untrained (UTR) groups. TR patients underwent a residential exercise program at 85% of maximum heart rate (HRmax) consisting of 2 daily sessions 6 times a week for 2 weeks. Eighty-six patients (45 TR and 41 UTR) completed the study. BRS was assessed at baseline and at the end of the protocol by the spontaneous baroreflex method. The standard deviation of mean R-R interval (RRSD) was also assessed as a measure of heart rate variability. At baseline, there were no significant differences between TR and UTR patients in any variable. In TR patients, BRS increased from 3.0±0.3 to 5.3±0.7 ms/mm Hg (P <0.001), RRSD from 18.7±1.4 to 23.6±1.6 ms (P <0.01), and R-R interval from 792.0±15.5 to 851.3±20.5 ms (P <0.001). No significant changes occurred in UTR patients. Increases in BRS and RRSD were significant in patients either with or without a previous MI. Conclusions—Exercise training increases BRS and heart rate variability in patients with coronary artery disease. Improved cardiac autonomic function might add to the other benefits of exercise training in secondary prevention of ischemic heart disease.

Muscle metaboreflex contribution to sinus node regulation during static exercise: insights from spectral analysis of heart rate variability.

BACKGROUND It is currently assumed that during static exercise, central command increases heart rate (HR) through a decrease in parasympathetic activity, whereas the muscle metaboreflex raises blood pressure (BP) only through an increase in sympathetic outflow to blood vessels, because when the metaboreflex activation is maintained during postexercise muscle ischemia, BP remains elevated while HR recovers. We tested the hypotheses that the muscle metaboreflex contributes to HR regulation during static exercise via sympathetic activation and that the arterial baroreflex is involved in the HR recovery of postexercise muscle ischemia. METHODS AND RESULTS Eleven healthy male volunteers performed 4-minute static leg extension (SLE) at 30% of maximal voluntary contraction, followed by 4-minute arrested leg circulation (ALC). Autonomic regulation of HR was investigated by spectral analysis of HR variability (HRV), and baroreflex control of heart period was assessed by the spontaneous baroreflex method. SLE resulted in a significant increase in the low-frequency component of HRV that remained elevated during ALC. The normalized high-frequency component of HRV was reduced during SLE and returned to control levels during ALC. Baroreflex sensitivity was significantly reduced during SLE and returned to control levels during ALC when BP was kept elevated above the resting level while HR recovered. CONCLUSIONS The muscle metaboreflex contributes to HR regulation during static exercise via a sympathetic activation. The bradycardia that occurs during postexercise muscle ischemia despite the maintained sympathetic stimulus may be explained by a baroreflex-mediated increase in parasympathetic outflow to the sinoatrial node that overpowers the metaboreflex-induced cardiac sympathetic activation.

Evaluation of reproducibility of spontaneous baroreflex sensitivity at rest and during laboratory tests

Objective The aim of the present study was to examine the reproducibility of arterial baroreflex sensitivity (BRS) provided by the spontaneous baroreflex method at rest and during laboratory tests. Methods Twenty healthy volunteers were studied 24 h apart, in the same laboratory and under the same environmental conditions, at rest, during active standing, while performing mental arithmetics and during static handgripping. Systolic blood pressure, mean arterial pressure and pulse interval were continuously and non-invasively measured by using a Finapres device. BRS was evaluated by analysing the slopes of spontaneously occurring sequences of three or more consecutive beats in which systolic blood pressure and pulse interval of the following beat both increased or decreased, in the same direction, in a linear fashion. Individual BRS were obtained by averaging all slopes computed within a given test. Results Under each test condition BRS did not differ significantly between the two consecutive days, showing strikingly similar values. The mean group coefficients of variation (CVAR), obtained by averaging individual CVAR, between the two experimental days were 15.0, 13.9, 15.3 and 19.7% for resting, standing, static hand-gripping and mental arithmetic, respectively. No relationships were found between individual CVAR and individual mean arterial pressure, pulse interval and number of baroreflex sequences under any tested condition, on both experimental days. Conclusions These results show that the spontaneous baroreflex method provides good BRS reproducibility under various stimuli that affect the neural control of circulation differently. They also suggest that BRS variability is dependent neither on haemodynamic modifications nor on the degree of baroreflex engagement, but it seems to reflect an inherent feature of the way in which arterial baroreflexes modulate the heart period.

Dose-response relationship of autonomic nervous system responses to individualized training impulse in marathon runners.

In athletes, exercise training induces autonomic nervous system (ANS) adaptations that could be used to monitor training status. However, the relationship between training and ANS in athletes has been investigated without regard for individual training loads. We tested the hypothesis that in long-distance athletes, changes in ANS parameters are dose-response related to individual volume/intensity training load and could predict athletic performance. A spectral analysis of heart rate (HR), systolic arterial pressure variability, and baroreflex sensitivity by the sequences technique was investigated in eight recreational athletes during a 6-mo training period culminating with a marathon. Individualized training load responses were monitored by a modified training impulse (TRIMP(i)) method, which was determined in each athlete using the individual HR and lactate profiling determined during a treadmill test. Monthly TRIMP(i) steadily increased during the training period. All the ANS parameters were significantly and very highly correlated to the dose of exercise with a second-order regression model (r(2) ranged from 0.90 to 0.99; P < 0.001). Variance, high-frequency oscillations of HR variability (HRV), and baroreflex sensitivity resembled a bell-shaped curve with a minimum at the highest TRIMP(i), whereas low-frequency oscillations of HR and systolic arterial pressure variability and the low frequency (LF)-to-high frequency ratio resembled an U-shaped curve with a maximum at the highest TRIMP(i). The LF component of HRV assessed at the last recording session was significantly and inversely correlated to the time needed to complete the nearing marathon. These results suggest that in recreational athletes, ANS adaptations to exercise training are dose related on an individual basis, showing a progressive shift toward a sympathetic predominance, and that LF oscillations in HRV at peak training load could predict athletic achievement in this athlete population.

Matched dose interval and continuous exercise training induce similar cardiorespiratory and metabolic adaptations in patients with heart failure

BACKGROUND The best format of exercise training in patients with chronic heart failure (CHF) is controversial. We tested the hypothesis that aerobic continuous training (ACT) and aerobic interval training (AIT) induce similar effects on functional capacity, central hemodynamics and metabolic profile in patients with postinfarction CHF provided that the training load is equated by an individually-tailored volume/intensity dose of exercise. METHODS Twenty patients with postinfarction CHF under optimal medical treatment were randomized to ACT or AIT for 12 weeks. Exercise training consisted in individualized loads prescribed according to the Training Impulses (TRIMPi) method, which was determined using the individual HR and lactate profiling obtained during a treadmill test at baseline. RESULTS Peak VO2 increased significantly by 22% with both ACT and AIT, without differences between the two training programs. Changes in anaerobic threshold and VE/VCO2 slope were not significantly different between ACT and AIT. Resting HR significantly decreased with both exercise modes. Resting cardiac output and stroke volume, left ventricular diastolic dimension and ejection fraction did not change from baseline with both exercise modes. Lipid profile and glucose metabolism were not substantially altered by ACT and AIT. CONCLUSIONS ACT and AIT both induce significant improvement in aerobic capacity in patients with postinfarction CHF, without significant differences between the two training modes, provided that patients are trained at the same, individually tailored, dose of exercise. The TRIMPi method might represent a step forward in the individualization of an aerobic training tailored to the patients clinical and functional status within cardiac rehabilitation programs.

Baroreflex Buffering of Sympathetic Activation During Sleep. Evidence From Autonomic Assessment of Sleep Macroarchitecture and Microarchitecture

Abstract—We examined the effects of sleep microstructure, ie, the cyclic alternating pattern (CAP), on heart rate (HR)- and blood pressure (BP)-regulating mechanisms and on baroreflex control of HR in healthy humans and tested the hypothesis that sympathetic activation occurring in CAP epochs during non-rapid eye movement (non-REM) sleep periods is buffered by the arterial baroreflex. Ten healthy males underwent polysomnography and simultaneous recording of BP, ECG, and respiration. Baroreflex sensitivity (BRS) was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate R-R interval (RRI) and BP variabilities. During overall non-REM sleep, BP decreased and RRI increased in comparison to wakefulness, with concomitant decreases in low-frequency RRI and BP oscillations and increases in high-frequency RRI oscillations. These changes were reversed during REM to wakefulness levels, with the exception of RRI. During CAP, BP increased significantly in comparison to non-CAP and did not differ from REM and wakefulness. The low-frequency component of BP variability was significantly higher during CAP than non-CAP. RRI and its low-frequency spectral component did not differ between CAP and non-CAP. BRS significantly increased during CAP in comparison to non-CAP. BRS was not different during CAP and REM and was greater during both in comparison with the awake state. Even during sleep stages, like non-REM sleep, characterized by an overall vagal predominance, phases of sustained sympathetic activation do occur that resemble that occurring during REM. Throughout the overnight sleep period, the arterial baroreflex acts to buffer surges of sympathetic activation by means of rapid changes in cardiac vagal circuits.

Sleep-related changes in baroreflex sensitivity and cardiovascular autonomic modulation.

Objective We examined the effects of the various sleep stages on baroreflex sensitivity (BRS), and heart rate and blood pressure (BP) variability, and tested the hypothesis that there is a different behavior of the baroreflex control of the sinus node in response to hypertensive and hypotensive stimuli and in relation to different cycles of the overnight sleep. Design Polygraphic sleep recordings were performed in 10 healthy males. The BP and the RR interval were continuously recorded during sleep. Methods BRS was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate the RR-interval and BP variabilities. Results During rapid eye movement (REM) sleep BRS significantly increased in response to hypertensive stimuli in comparison with non-rapid eye movement (NREM) sleep and the awake state, whereas it did not change in response to hypotensive stimuli. In the first sleep cycle, BRS significantly increased during NREM in comparison with wakefulness, whereas during REM BRS in response to hypertensive stimuli did not show significant changes as compared with the awake state and/or with NREM. During REM occurring in the sleep cycle before morning awakening, BRS showed a significant increase in response to hypertensive stimuli in comparison with both NREM and the awake state. Conclusions During sleep, arterial baroreflex modulation of the sinus node is different in response to hypotensive and hypertensive stimuli particularly during REM. Furthermore, baroreflex control of the sinus node shows a non-uniform behavior during REM occurring in different nocturnal sleep cycles. These findings suggest that the arterial baroreflex is more effective in buffering the increased sympathetic activation associated with REM at the end of sleep than in the early night.

Positive and Negative Feedback Mechanisms in the Neural Regulation of Cardiovascular Function in Healthy and Spinal Cord–Injured Humans

Background — We tested the hypothesis that in humans, hypertension/tachycardia and hypotension/bradycardia nonbaroreflex sequences that occur within spontaneous arterial pressure (AP) and R-R interval fluctuations are an expression of positive feedback mechanisms neurally regulating the cardiovascular system. Methods and Results — We studied 15 spinal cord–injured (SCI) subjects (8 tetraplegics and 7 paraplegics) and 8 healthy subjects. The occurrence of nonbaroreflex (NBseq) and baroreflex (Bseq) sequences, ie, hypertension-bradycardia and hypotension-tachycardia sequences, was assessed during rest and head-up tilt (HUT). The ratio between Bseq and NBseq (B/NB ratio) was also calculated. In resting conditions, the occurrence of NBseq was significantly lower (P <0.05) in tetraplegics (7.9±1.5) than in paraplegics (16.2±3.2) and normal subjects (19.0±3.5), whereas the occurrence of Bseq was not significantly different between the 3 groups (38.6±11.9 versus 45.4±6.0 versus 47.0±11.9). In tetraplegics, the B/NB ratio showed a marked, significant decrease (from 8.4±4.2 to 1.9±0.8, P <0.05) in response to HUT, whereas in normal subjects, it showed a significant increase (from 3.5±0.7 to 9.4±2.7, P <0.05). In paraplegics, the B/NB ratio did not change significantly in response to HUT (from 4.5±1.6 to 4.8±1.1). Conclusions — Our data suggest that nonbaroreflex sequences occur in humans and might represent the expression of an integrated, neurally mediated, feed-forward type of short-term cardiovascular regulation that is able to interact dynamically with feedback mechanisms of baroreflex origin.

Spontaneous baroreflex modulation of heart rate and heart rate variability during orthostatic stress in tetraplegics and healthy subjects.

Objective This study was addressed to investigate the contribution of vagal and sympathetic mechanisms to the genesis of low-frequency (LF) oscillations of RR-interval. Design To this aim, we utilized the pathophysiological model of tetraplegics, who have intact vagal afferent and efferent pathways of the baroreceptor reflex arc but interrupted medullary-spinal sympathetic pathways. Methods We studied nine complete, traumatic, tetraplegics (C4–C7, TET) and 10 normally healthy subjects (NR) at rest and during physiological baroreceptors unloading induced by 70 ° head-up tilt. Autoregressive power spectral analysis was used to investigate RR-interval and systolic arterial pressure (SAP) variabilities. Baroreflex modulation of sinus node was assessed by the spontaneous baroreflex sequences method. Results Both at-rest and during-tilt LF and high frequency (HF) components were detected in RR-interval of NR, whereas in TET only the HF component was observed in both conditions (with one exception). Baroreflex sensitivity (BRS) did not significantly differ between TET and NR at rest, and underwent a significant and similar decrease during tilt in both groups, being accompanied in NR by a significant increase in LF relative power. Spectral analysis of SAP provided results similar to RR-interval. Tilt also slowed the centre frequency of the LF components of RR-interval and SAP. Conclusions During unperturbed physiological conditions, a change in efferent vagal activity to the heart from baroreflex stimulation by spontaneous arterial pressure changes, is unlikely to contribute on its own to the genesis of LF heart period oscillations in humans who lack the ability to modulate sympathetic nerve traffic to the heart. However, the possibility that a baroreflex modulation of LF oscillations require an intact sympathetic control should be carefully considered.

Dose-response relationship of baroreflex sensitivity and heart rate variability to individually-tailored exercise training in patients with heart failure

BACKGROUND Heart Rate Variability (HRV) and Baroreflex Sensitivity (BRS) are impaired in patients with Chronic Heart Failure (CHF) and carry negative prognosis. Exercise training improves these parameters. However, the relationship between exercise training with HRV and BRS has been investigated without regard for individual training loads. We tested the hypothesis that in CHF patients changes in HRV and BRS are dose-response related to individual volume/intensity training load (TL). METHODS Twenty patients with stable postinfarction CHF under optimal medical treatment were randomized to either aerobic continuous training (ACT) or aerobic interval training (AIT) for 12weeks. Individualized TL was monitored by the Training Impulses (TRIMPi) method, which was determined using the individual HR and lactate profiling determined during a treadmill test at baseline. HRV (standard deviation of mean R-R interval) and BRS were assessed at rest and 3weeks apart, throughout the study. RESULTS HRV, BRS and R-R interval increased significantly with training, being very highly correlated to the dose of exercise with a second-order regression model (r(2) ranged from 0.75 to 0.96; P<0.001), resembling a bell-shaped in the ACT, and an asymptotic-shaped curve in the AIT groups, respectively. These changes were accompanied by a significant increase in functional capacity. No significant differences were detected between ACT and AIT in any variable. CONCLUSIONS These results suggest that improvements in HRV and BRS by exercise training in CHF patients are dose related to TL in a non-linear fashion on an individual basis, with optimal results at moderate doses of exercise.