Dyslipidemia and heart failure: current evidence and perspectives of use of statins.

Heart failure (HF) is a condition with growing morbidity and mortality. Dyslipidemia in HF is not concentrated around hypercholesterolemia as in coronary artery disease. As a corollary, the robust benefits seen with statins across the spectrum of CAD have not been replicated in HF. Multiple potential pleiotropic effects of statins include anti-inflammatory, antioxidant, endothelial stabilization, antiapoptotic, anti-thrombotic, and modulation of the autonomic system apart from lipid lowering. These benevolent actions need to be counterbalanced with the potential derangement of ubiquinone, selenoprotein and endotoxin pathways. While small randomized and non-randomized studies demonstrated a multitude of benefits in clinical and surrogate endpoints, two large RCTs failed to demonstrate unequivocal benefits. However, multiple large meta-analyses do demonstrate definite improvement in clinical endpoints including death and heart failure hospitalization. The clinical likelihood of benefit was higher in younger patients with less advanced HF and use of lipophilic statins.

Sarcopenic obesity: etiology and lifestyle therapy.

OBJECTIVE: Sarcopenic obesity (OS) is a multifactorial condition characterized by the simultaneous presences of sarcopenia and obesity. The prevalence of OS is increasing in adults over 65 years of age; people with OS present greater health risks than people who are only sarcopenic or obese. Therefore, the study of OS and the search for effective treatment are important due to the constant increase of the elderly population. MATERIALS AND METHODS: This review discusses the etiology and evolutionary mechanisms of OS while exploring its molecular, metabolic, oxidative, inflammatory, hormonal, and nutritional stresses. Studies have tried to unravel the causes related to the onset of sarcopenia, which is responsible for the decrease of muscle mass and strength in elderly subjects. The diagnostic criteria and the methods of evaluation of OS are described in these research studies, although there is no univocal definition for these parameters. The most studied treatments in OS are illustrated and highlight how the physical activity performed through both aerobic and resistance exercises, as well as a correct nutritional treatment, prove to be the most effective interventions in the regression of the pathology and in the improvement of physical function. RESULTS: New therapies for OS are hypothesized that will open the way to other possible types of intervention in the future. CONCLUSIONS: The deficiency of muscle mass in obese elderly subjects will be one of the health challenges of the future to reduce the risk of chronic diseases.

Effects of testosterone on the Q-T interval in older men and older women with chronic heart failure.

The Q-Tc interval duration on the electrocardiogram is recognized to differ between the sexes. In vitro data and data from humans before and after puberty and menopause suggest that sex hormones play a role in the longer Q-Tc intervals in women, or conversely, the shorter Q-Tc intervals in men. Direct investigations of sex hormone effects on the Q-Tc interval in humans, however, are limited and reach conflicting conclusions. Our objective was to determine effects of testosterone on ECG Q-T intervals of older men and older women. ECG's from 84 older men and older women in double-blind placebo-controlled investigations of testosterone supplementation for the treatment of chronic heart failure (CHF) were analysed. Thirty men received 1000mg intramuscular long-acting testosterone undecanoate and 28 men received saline at 0, 6 and 12weeks. ECG's were recorded at baseline and 12weeks. Sixteen women received transdermal testosterone (33µg) and 10 women received matching placebo twice weekly for 24 weeks with ECG's at baseline and after 24weeks. Testosterone, but not placebo, shortened Q-T and Q-Tc intervals without heart rate changes. Q-T intervals decreased from 385±28 (mean±SD) to 382±28 ms (p<0.002) and Q-Tc intervals decreased from 398±26 to 392±27 (p<0.006) in men on testosterone. In women, Q-T intervals decreased from 400±25 to 397±23ms (p=0.06) and Q-Tc intervals from 415±26 to 409±27ms (p=0.3) on testosterone. Q-T intervals were longer in women compared with men under all conditions (p<0.03). The data support a direct effect of testosterone to shorten Q-T intervals in older men and older women in the absence of HR changes or hypogonadal status. Mean decreases are small and unlikely to affect risks of arrhythmic events in patients receiving Q-T prolonging medications.

Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight.

This study explored the process of arterial baroreflex adaptation to microgravity, starting from the first day of flight, during the 16-day STS-107 Columbia Space Shuttle mission. Continuous blood pressure (BP), ECG, and respiratory frequency were collected in four astronauts on ground (baseline) and during flight at days 0-1, 6-7, and 12-13, both at rest and during moderate exercise (75 W) on a cycle ergometer. Sensitivity of the baroreflex heart rate control (BRS) was assessed by sequence and spectral alpha methods. Baroreflex effectiveness index (BEI); low-frequency (LF) power and high-frequency (HF) power of systolic BP (SBP), diastolic BP (DBP), and R-R interval (RRI); the RRI LF/HF ratio; and the RRI root mean square of successive differences (RMSSD) index were also estimated. We found that, at rest, BRS increased in early flight phase, compared with baseline (means +/- SE: 18.3 +/- 3.4 vs. 10.4 +/- 1.2 ms/mmHg; P < 0.05), and it tended to return to baseline in subsequent days. During exercise, BRS was lower than at rest, without differences between preflight and in-flight values. At rest, in the early flight phase, RMSSD and RRI HF power increased (P < 0.05) compared with baseline, whereas LF powers of SBP and DBP decreased. No statistical difference was found in these parameters during exercise before vs. during flight. These findings demonstrate that heart rate baroreflex sensitivity and markers of cardiac vagal modulation are enhanced during early exposure to microgravity, likely because of the blood centralization, and return to baseline values in subsequent flight phases, possibly because of the fluid loss. No deconditioning seems to occur in the baroreflex control of the heart.

The long-acting phosphodiesterase inhibitor tadalafil does not influence athletes' VO2max, aerobic, and anaerobic thresholds in normoxia.

Whereas experimental studies showed that in healthy trained subjects, the phosphodiesterase-5 inhibitor (PDE-5i) sildenafil improves exercise capacity in hypoxia and not in normoxia, no studies on the effects of the long half-life PDE-5i tadalafil exist. In order to evaluate whether tadalafil influences functional parameters and performance during a maximal exercise test in normoxia, we studied 14 healthy male athletes in a double-blind cross-over protocol. Each athlete performed two tests on a cycle ergometer, both after placebo or tadalafil (at therapeutic dose: 20 mg) administration. Oxygen consumption (VO2), blood lactate, respiratory exchange ratio, rate of perceived exertion, arterial blood pressure (BP), heart frequency (HR) and oxygen pulse (VO2/HR) were evaluated before exercise, at individual ventilatory and anaerobic thresholds (IVT and IAT), at VO2max and during recovery. Compared to placebo, a single tadalafil administration significantly reduced systolic BP before and after exercise (p < 0.05), decreased VO2/HR at IVT (13.3 +/- 1.8 vs. 14.5 +/- 2.1 mL . beat (-1); p = 0.03), but did not modify individual VO2max, IVT, or IAT. In healthy athletes, 20 mg of tadalafil does not substantially influence physical fitness-related parameters, exercise tolerance, and cardiopulmonary responses to maximal exercise in normoxia; it remains to be verified if higher doses/prolonged use influence health and/or sport performance in field conditions.

Autonomic and psychological adaptations in Olympic rowers.

AIM: Power spectral analysis of heart rate variability has been used to assess the time course of neurovegetative adaptations to training. This study was undertaken: 1) to evaluate whether and which indicator(s) of autonomic cardiac regulation and psychophysical stress can identify successful athletes during a training season culminating with the Olympic Games and 2) to evaluate the feasibility of a quasi-on-line assessment of autonomic cardiac regulation from training field, by a telematic approach. METHODS: This study was conducted on the group of male athletes composing the Italian national team of rowing (n=34), in the season preceding the 2004 Olympic Games. Complete results are from 18 subjects (age 25.3+/-0.5 years), who were selected to participate to the Athens' Olympic games. Athletes were studied while partially detrained, at mid-training season and close to the games. The RR interval was obtained through a miniature transtelephonic-ECG recorder in the supine and standing posture, thus allowing the evaluation of cardiovascular responses to a sympathetic challenge. Data were downloaded through a telephone line, to the referral center where RR-interval variability data were analyzed with the autoregressive method. Also, in each study sessions, athletes filled a self-administered questionnaire of stress perception and somatic symptoms (4S-Q). RESULTS: All ECG recordings were transmitted successfully by phone to the referral center. No significant difference was detected in any marker of autonomic cardiac regulation between athletes who won a medal at the Olympic Games and those who did not. However, respiratory rate was faster in medal winners (P=0.02), while the questionnaire addressing stress (4S-Q) provided greater scores in the group that did not win a medal (F=5.55, P<0.022) at mid-training season and close to the Olympic Games. CONCLUSIONS: The results of this study would suggest the possibility of an early detection of psychosomatic symptoms resulting from long duration and elevated stress of preparing for top level competitions, whose better handling might identify the most successful athletes. In addition, it indicates the feasibility of a quasi-on-line assessment of autonomic cardiac adaptations to strenuous training directly from field to be possibly used for improving individual training programs, allowing athletes evaluation in their natural environment.

Vigorous exercise training is not associated with prevalence of ventricular arrhythmias in elderly athletes.

AIM: Physical activity, when vigorous, is not devoided of arrhythmic risk. Since the risk of developing arrhythmias increase as an otherwise healthy person ages, the question arises as to whether high intensity physical activity could be dangerous in the elderly person. The present study addressed the incidence of arrhythmias in elderly athletes in comparison to age-matched control subjects. METHODS: We studied 49 male athletes engaged in various sport disciplines, mean age 62.3+/-2.3 and 24 sedentary or moderately physically active healthy males, mean age 62.9+/-1.7 years (Controls). All subjects underwent 2-D, M-mode and Doppler echocardiographic examination, resting ECG and exercise stress test followed by 24-hour electrocardiographic monitoring. RESULTS: No pathological findings were detected in both experimental groups at echocardiographic examination. Exercise performance was greater in athletes than controls (206.9+/-5.2 vs 156.3+/-12 watt, p<0.01). During exercise test, no significant between-groups difference was detected in the incidence of ventricular arrhythmias, that is multiple premature ventricular contractions (MPVC), polymorphous premature ventricular contractions (PPVC) and repetitive premature ventricular contractions (RPVC). No subject featured horizontal or downsloping ST segment depression in both groups. At 24-hour electrocardiographic monitoring the incidence of the overall number of premature ventricular contractions was significantly greater in controls than athletes (87.0% vs 63.3%, p<0.05), whereas no significant difference were detected in the incidence of discrete ventricular arrhythmias between athletes (4.1% MPVC, 14.3% PPVC, 8.2% couplets) and controls (0.5% MPVC, 16.7% PPVC, 12.5% couplets). CONCLUSION: These finding indicate that in elderly, otherwise healthy, athletes vigorous training even to competition does not result in a greater incidence of ventricular arrhythmias, although caution should be made for a careful preparticipation evaluation.

The stress of competition dissociates neural and cortisol homeostasis in elite athletes.

AIM: Stressful situations affect autonomic nervous system activity and hormonal responses. This study aimed to investigate the effects of the stress of sports competition on both endocrine system functioning and neurovegetative control of heart rate (HR) in elite athletes. METHODS: In 7 top-level pentathletes salivary cortisol levels and autoregressive power spectral analysis of HR variability (HRV) were assessed in the morning and in the afternoon on a regular training day (control) and on the day of a competitive selection trial, held 4 weeks apart. RESULTS: HR, as well as low (LF) and high (HF) frequency components of HRV did not differ significantly both between and within the control and the trial days. On the selection day, morning cortisol levels were significant and markedly greater than on the control day and increased further in the afternoon in contrast to the control day, when cortisol levels decreased in the afternoon as expected from the normal diurnal variation. CONCLUSION: These results would indicate a dissociation of the neural and hypothalamic-pituitary-adrenal axis functioning in response to the stress of competition in elite athletes, and the considerable extent to which competition may alter selectively the physiology of stress-related hormones while sparing autonomic cardiac regulation.

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 degrees 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.

Neural mechanisms of cardiovascular regulation during exercise.

This brief review addresses current hypotheses concerning the reflex control of circulation during exercise in humans. In particular, the specific objective of this review is to describe how time and frequency domain analysis of blood pressure and heart rate variability signals permitted to gain new insights onto reflex mechanisms of cardiovascular regulation during exercise, without the need of perturbing the cardiovascular system from the outside, utilizing fully noninvasive approaches and avoiding artificially isolating the influence of the different neural pathways involved in the control of the cardiovascular system. Throughout the article, particular emphasis is given to the complexity and plasticity of the neural control of the circulation during exercise, by presenting data that show how the reflex mechanisms involved in cardiovascular regulation, namely, the arterial baroreflex and the muscle metaboreflex, may be differently modulated in relation to the muscular activity being performed, such as the type of exercise, the intensity of exercise and the size of active muscle masses.

Selective impairment of excitatory pressor responses after prolonged simulated microgravity in humans.

The haemodynamic and autonomic effects of prolonged exposure to simulated microgravity were assessed non-invasively in seven healthy volunteers completing a 42-day -6 degrees head down tilt. Before, during and after head down tilt, subjects were exposed to moderate excitatory stimuli (mental arithmetic and static handgrip) to gauge possible progressive impairment of pressor responses. Before and after head down tilt, subjects were also exposed to orthostatic stress, to assess influences of simulated microgravity on orthostatic defence. Simple haemodynamics (heart rate and systolic arterial blood pressure), linear (i.e., oscillatory) components of beat-by-beat variability, non-linear properties (i.e., corrected conditional entropy (CCE)) of RR interval variability, and baroreflex slope furnished a non-invasive evaluation of autonomic regulatory mechanisms. Pressor responses to mental arithmetic and to handgrip were markedly impaired after 42 days head down tilt, whereas responses in markers of autonomic regulation were not modified. Standing, performed 8 days after head down tilt to limit the risk of syncope, still induced a variable degree of hypotension, with signs of progressively greater sympathetic activation than before head down tilt. Simulated microgravity-induced reduction of pressor responses, in spite of largely maintained autonomic activation, favours the hypothesis of a peripheral impairment of cardiovascular homeostasis. rights reserved.

Effects of aerobic exercise training on 24 hr profile of heart rate variability in female athletes.

BACKGROUND: The aim of this study was to investigate the effects of exercise training on autonomic regulation of heart rate under daily life conditions. METHODS: Twenty-six healthy female athletes (age 24.5 +/- 1.9 yrs) involved in regular physical activity were recruited during a period of yearly rest and randomly assigned to a five-week aerobic exercise training program (n = 13) or to a non-exercise control group (n = 13). MEASURES: Before and after the five-week training, all subjects underwent a bycicle ergometer stress test and a 24-hour dynamic ECG monitoring. Autonomic regulation of heart rate has been investigated by means of both time and frequency domain analyses of heart rate variability (HRV). Spectral analysis of R-R interval variability (autoregressive algorithm) provided markers of sympathetic (low frequency, LF, 0.10 Hz) and parasympathetic (high frequency, HF, 0.25 Hz) modulation of the sinus node. RESULTS: Trained subjects showed a reduced heart rate response to submaximal workload. Before training there was no significant difference between the two groups. After training resting heart rate did not significantly differ between trained and untrained subjects. No significant differences were observed in the different time domain indexes of heart rate variability. The day-night difference in SD and SDRR were significantly less in the trained as compared to the untrained group. Normalized LF and HF components did not significantly differ between trained and untrained subjects, during the awake period. The decrease in the LF and the increase in the HF component during nighttime were significantly less in the trained group. The LF/HF ratio was significantly decreased during the night in the untrained group whereas it was not significantly different from the awake state in the trained group. CONCLUSIONS: These findings of the relative night-time increase in LF and the decrease in the day-night difference in time domain indexes of heart rate variability suggest that, in young female athletes, exercise training is able to induce an increase in the sympathetic modulation of the sinus node which may coexist with signs of relatively reduced, or unaffected, vagal modulation.

Neural control of the cardiovascular system during exercise.

The objective of this review was to give an overview on the current knowledge on the neural mechanisms of cardiovascular regulation during exercise. Evidence derived mainly from human studies which supports the contribution of the different control mechanisms, namely the central command, the reflex drive from active muscles and the arterial baroreflex, with the attendant modifications in autonomic nervous system activity, in determining the cardiovascular responses to exercise are discussed, along with some controversial issues and evolving concepts in exercise physiology. In particular, data that show how the various neural mechanisms involved in cardiovascular regulation during exercise are differently modulated by factors related to the muscular activity being performed, such as the type and intensity of exercise and the size of the active muscle masses are presented, stressing the plasticity of the neural network. Finally, clinical implications pertaining to neural cardiovascular regulation and exercise are advanced.

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.

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.

Group III muscle afferents evoke reflex depressor responses to repetitive muscle contractions in rabbits.

Repetitive-twitch contraction of the hindlimb muscles in anesthetized rabbits consistently evokes a reflex depressor response, whereas this type of contraction in anesthetized cats evokes a reflex pressor response in about one-half of the preparations tested. Rapidly conducting group III fibers appear to comprise the afferent arm of the reflex arc, evoking the depressor response to twitch contraction in rabbits because electrical stimulation of their axons reflexly decreases arterial pressure. In contrast, electrical stimulation of the axons of slowly conducting group III and group IV afferents reflexly increases arterial pressure in rabbits. In the present study, we examined the discharge properties of group III and IV muscle afferents and found that the former (i.e., 13 of 20), but not the latter (i.e., 0 of 10), were stimulated by 5 min of repetitive-twitch contraction (1 Hz) of the rabbit triceps surae muscles. Moreover, most of the group III afferents responding to contraction appeared to be mechanically sensitive, discharging in synchrony with the muscle twitch. On average, rapidly conducting group III afferents responded for the 5-min duration of 1-Hz repetitive-twitch contraction, whereas slowly conducting group III afferents responded only for the first 2 min of contraction. We conclude that rapidly conducting group III afferents, which are mechanically sensitive, are primarily responsible for evoking the reflex depressor response to repetitive-twitch contractions in anesthetized rabbits.

Effect of 4 hours HD -6 degrees on heart rate variability in symptomatic and non symptomatic subjects.

Orthostatic intolerance is the most serious symptom of cardiovascular deconditioning induced by microgravity exposure. In fact the neural control mechanisms of the cardiovascular system are significantly affected by this condition. Non-invasive measurement of Heart Rate Variability (HRV) have been used as a valuable tool to characterize the ability of neuroendocrine regulatory systems to modulate the cardiovascular function by analyzing the spontaneous fluctuations of arterial pressure and heart period on a beat-to-beat basis. Concerning this, conflicting results have been reported on the heart rate and blood pressure variability responses during exposure to microgravity. These differences seem to be due to different experimental designs used. Moreover, the different behavior of normal subjects in response to orthostatic stress after HD, i.e. Symptomatic (S) or Non Symptomatic (NS), could play some roles in producing these discrepancies. Therefore the aim of the present study was to examine BP and HR variability before and after 4 hours of HD in two groups of normal subjects with and without symptoms of orthostatic intolerance to orthostatic stress.

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.