Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit?

Occupational or recreational exercise reduces mortality from cardiovascular disease. The potential mechanisms for this reduction may include changes in blood pressure (BP) and autonomic control of the circulation. Therefore, we conducted the present long-term longitudinal study to quantify the dose-response relationship between the volume and intensity of exercise training, and regulation of heart rate (HR) and BP. We measured steady-state hemodynamics and analyzed dynamic cardiovascular regulation by spectral and transfer function analysis of cardiovascular variability in 11 initially sedentary subjects during 1 yr of progressive endurance training sufficient to allow them to complete a marathon. From this, we found that 1) moderate exercise training for 3 mo decreased BP, HR, and total peripheral resistance, and increased cardiovascular variability and arterial baroreflex sensitivity; 2) more prolonged and intense training did not augment these changes further; and 3) most of these changes returned to control values at 12 mo despite markedly increased training duration and intensity equivalent to that routinely observed in competitive athletes. In conclusion, increases in R-wave-R-wave interval and cardiovascular variability indexes are consistent with an augmentation of vagal modulation of HR after exercise training. It appears that moderate doses of training for 3 mo are sufficient to achieve this response as well as a modest hypotensive effect from decreasing vascular resistance. However, more prolonged and intense training does not necessarily lead to greater enhancement of circulatory control and, therefore, may not provide an added protective benefit via autonomic mechanisms against death by cardiovascular disease.     

Influence of the Personality Traits of Parent and Children on the Autonomic Regulation of Heart Rate in Children of Preschool Age and Adolescents

The relationship between personality traits and autonomic regulation of heart rate in children of preschool age and adolescents was studied. Significant positive correlations of the parameter of trait anxiety in children of preschool age with the index of tension (IT) of the cardiovascular system and of the value of extro/introversion of parents (mothers) with the IT of children were obtained. A relationship was revealed between school anxiety and the state of autonomic regulation of the heart rate in children of preschool age and adolescents.     

Characteristics of the myocardium functional state and cerebral circulation of seven- to ten-year-old children with different variants of autonomic nervous regulation of the heart rate

A complex study of the functional state of the cardiovascular system of seven- to ten-year-old children with different types of autonomic nervous regulation of the heart rate was performed. It was found that the autonomic nervous system strongly affects the adaptive capacity of the body, bioelectrical processes in the myocardium, the duration of cardiac-cycle phases, the pulse volume, and the tone of large and small cerebral vessels.     

Neural regulation of the cardiovascular system during exercise

Neural components important in control of the cardiovascular system during exercise can be divided into central nervous system (CNS) components and peripheral components. CNS components would include the cerebral cortex, cerebellum, medullary region of the brain stem, and the spinal cord. Peripheral components would include the efferent limbs of the autonomic nervous system and afferent fibers carrying information to the CNS. The neural pathways involved in the control of cardiovascular system during exercise and the relationship between the various neural components have been actively pursued in the last few years. Several new studies suggest that information arising from the active muscles and the cardiovascular system itself may be important in the control of the cardiovascular system during exercise. The cerebellum may play a modulating role in the cardiovascular response. The information from the peripheral afferent fibers, the cerebellum, and the cerebral cortex is integrated in the brain to result in overall neural control. Exercise training probably modifies the central integration of information and modifies the cardiovascular response to exercise and other stresses.     

Changes in systolic arterial pressure variability are associated with the decreased aerobic performance of rats subjected to physical exercise in the heat

Enhanced cardiovascular strain is one of the factors that explains degraded aerobic capacity in hot environments. The cardiovascular system is regulated by the autonomic nervous system, whose activity can be indirectly evaluated by analyzing heart rate variability (HRV) and systolic arterial pressure (SAP) variability. However, no study has addressed whether HRV or SAP variability can predict aerobic performance during a single bout of exercise. Therefore, this study aimed to investigate whether there is an association between cardiovascular variability and performance in rats subjected to treadmill running at two ambient temperatures. In addition, this study investigated whether the heat-induced changes in cardiovascular variability and reductions in performance are associated with each other. Male Wistar rats were implanted with a catheter into their carotid artery for pulsatile blood pressure recordings. After recovery from surgery, the animals were subjected to incremental-speed exercise until they were fatigued under temperate (25 °C) and hot (35 °C) conditions. Impaired performance and exaggerated cardiovascular responses were observed in the hot relative to the temperate environment. Significant and negative correlations between most of the SAP variability components (standard deviation, variance, very low frequency [VLF], and low frequency [LF]) at the earlier stages of exercise and total exercise time were observed in both environmental conditions. Furthermore, the heat-induced changes in the sympathetic components of SAP variability (VLF and LF) were associated with heat-induced impairments in performance. Overall, the results indicate that SAP variability at the beginning of exercise predicts the acute performance of rats. Our findings also suggest that heat impairments in aerobic performance are associated with changes in cardiovascular autonomic control.     

Autonomic tone in branches of the respiratory-hemodynamic system of junior schoolchildren

Periodic variations in the cardiac, vascular, and respiratory branches of the respiratory-hemodynamic system (RHDS) were studied in children 8–11 years of age at rest using spectral analysis. By analogy with studying the autonomous regulation of the cardiac rhythm, the averaged pattern of the autonomic tone (BAT) was determined in all RHDS branches. We aimed at studying various combinations of the autonomic balance (AB) in the same pattern and identifying individual typological peculiarities of the BAT patterns of the RHDS. Groups of children with different autonomic RHDS patterns were determined using cluster analysis; these groups differed significantly in many spectral and hemodynamic parameters.     

Detection of Autonomic Dysfunction in Hemodialysis Patients Using the Exercise Treadmill Test: The Role of the Chronotropic Index,Heart Rate Recovery,and R-R Variability

Autonomic dysfunction is highly prevalent in hemodialysis patients and has been implicated in their increased risk of cardiovascular mortality.

Objective

To evaluate the ability of different parameters of exercise treadmill test to detect autonomic dysfunction in hemodialysis patients.

Methods

Cross-sectional study involving hemodialysis patients and a control group. Clinical examination, blood sampling, echocardiogram, 24-hour Holter, and exercise treadmill test were performed. A ramp treadmill protocol symptom-limited with active recovery was employed.

Results

Forty-one hemodialysis patients and 41 controls concluded the study. There was significant difference between hemodialysis patients and controls in autonomic function parameters in 24h-Holter and exercise treadmill test. Probability of having autonomic dysfunction in hemodialysis patients compared to controls was 29.7 at the exercise treadmill test and 13.0 in the 24-hour Holter. Chronotropic index, heart rate recovery at the 1st min, and SDNN at exercise were used to develop an autonomic dysfunction score to grade autonomic dysfunction, in which, 83% of hemodialysis patients reached a scoring ≥2 in contrast to 20% of controls. Hemodialysis was independently associated with either altered chronotropic index or autonomic dysfunction scoring ≥2 in every tested model (OR=50.1, P=0.003; and OR=270.9, P=0.002, respectively, model 5).

Conclusion

The exercise treadmill test was feasible and useful to diagnose of the autonomic dysfunction in hemodialysis patients. Chronotropic index and autonomic dysfunction scoring ≥2 were the most effective parameters to differentiate between hemodialysis patients and controls suggesting that these variables portrays the best ability to detect autonomic dysfunction in this setting.     

Functional state of the cardiovascular system in 13-year-old adolescents with different types of autonomic nervous regulation

The features of the functional state of cardiovascular system in 13-year-old children with different types of autonomic nervous regulation were studied. Children with normotonic and parasympathetic types of autonomic regulation were found to have the highest adaptation capacities. The autonomic nervous system influences the bioelectrical processes in myocardium, the duration of cardiac cycle phases, and cerebral blood flow. Schoolchildren aged 13 years with higher sympathetic activity have shorter duration of the cardiac cycle, the phase of isometric contraction, and diastole. They have a lower pulse blood flow rate and a higher tone of large and medium cerebral vessels. No relationship was revealed between the initial autonomic nervous regulation of heart rate and the type of adaptation of myocardium to physical dynamic loads, as well as the type of adaptation of cerebral circulation to mental stress.     

Effect of Acute Inspiratory Muscle Exercise on Blood Flow of Resting and Exercising Limbs and Glucose Levels in Type 2 Diabetes

To evaluate the effects of inspiratory loading on blood flow of resting and exercising limbs in patients with diabetic autonomic neuropathy. Ten diabetic patients without cardiovascular autonomic neuropathy (DM), 10 patients with cardiovascular autonomic neuropathy (DM-CAN) and 10 healthy controls (C) were randomly assigned to inspiratory muscle load of 60% or 2% of maximal inspiratory pressure (PImax) for approximately 5 min, while resting calf blood flow (CBF) and exercising forearm blood flow (FBF) were measured. Reactive hyperemia was also evaluated. From the 20 diabetic patients initially allocated, 6 wore a continuous glucose monitoring system to evaluate the glucose levels during these two sessions (2%, placebo or 60%, inspiratory muscle metaboreflex). Mean age was 58 ± 8 years, and mean HbA1c, 7.8% (62 mmol/mol) (DM and DM-CAN). A PImax of 60% caused reduction of CBF in DM-CAN and DM (P<0.001), but not in C, whereas calf vascular resistance (CVR) increased in DM-CAN and DM (P<0.001), but not in C. The increase in FBF during forearm exercise was blunted during 60% of PImax in DM-CAN and DM, and augmented in C (P<0.001). Glucose levels decreased by 40 ± 18.8% (P<0.001) at 60%, but not at 2%, of PImax. A negative correlation was observed between reactive hyperemia and changes in CVR (Beta coefficient = -0.44, P = 0.034). Inspiratory muscle loading caused an exacerbation of the inspiratory muscle metaboreflex in patients with diabetes, regardless of the presence of neuropathy, but influenced by endothelial dysfunction. High-intensity exercise that recruits the diaphragm can abruptly reduce glucose levels.     

Circadian Changes of Left Ventricular Ejection Fraction in Normal Subjects

Sleep has a specific physiology with related cardiovascular changes. We have previously found in respiratory patients [chronic obstructive pulmonary disease (COPD) and sleep apnea syndrome (OSAS)] an unexpected decrease in left ventricular ejection fraction (LVEF) at waking in the morning when compared with the rest period during the day. Whether this observation was linked to the consequences of the respiratory abnormalities or reflected physiological fluctuations related to the changes in autonomic nervous system tone remained unknown. Thus, we have set out to analyze the changes in LVEF with sleep in normal individuals. Eight healthy young men had LVEF measured before and after submaximal exercise, at rest before bedtime, and on waking in the morning. Technetium-99m with in vivo red cell labelling was used. Sleep parameters were assessed using classical polysomnography. In order to detect any influence of autonomic nervous system stimulation on LVEF, sympathovagal tone (SVT) was also assessed during night-time LVEF measurements using spectral analysis of RR intervals. LVEF at rest was within the normal limits for all the subjects (range 51-62%). On submaximal exercise, the LVEF increased in four subjects, was unchanged in two, and decreased in two. The main result concerns the changes in LVEF overnight. In the morning, LVEF decreased dramatically in three subjects and reached a level of <30% in four. These decreases in LVEF were not related to changes in SVT or sleep structure. LVEF values returned to normal in 30 min. The LVEF changes during exercise are in accordance with previous data in the literature. The dramatic decrease in LVEF observed in the morning could be related either to vascular resistance changes or to nocturnal variations in cardiac contractility, which both need further studies to be established.     

The state of the cardiovascular system in children aged 8–9 in the norm and in impairments of intellectual development

The specific features of the psychophysiological regulation of the cardiovascular system in healthy 8-to 9-year-old children and in children of the same age with impairments of intellectual development are considered. An analysis of the functional heart rhythm values after mental and physical exercise is given. The directions of correctional influence on the mechanisms of functional optimization of the cardiovascular system are outlined.     

Low-magnitude whole body vibration with resistive exercise as a countermeasure against cardiovascular deconditioning after 60 days of head-down bed rest

Whole body vibration with resistive exercise is a promising countermeasure against some weightlessness-induced dysfunctions. Our objective was to study whether the combination of low-magnitude whole body vibration with a resistive exercise can prevent the cardiovascular deconditioning induced by a nonstrict 60-day head-down bed rest (Earth Star International Bed Rest Experiment Project). Fourteen healthy men participated in this study. We recorded electrocardiograms and blood pressure waves by means of a noninvasive beat-by-beat measurement system (Cardiospace, integrated by Centre National d'Etudes Spatiales and Astronaut Center of China) during an orthostatic test (20 min of 75-degree head-up tilt test) before and immediately after bed rest. We estimated heart rate, blood pressure, cardiac output, stroke volume, total peripheral resistance, baroreflex sensitivity, and heart rate variability. Low-magnitude whole body vibration with resistive exercise prevented an increase of the sympathetic index (reflecting the sympathovagal balance of cardiac autonomic control) and limited the decrease of the spontaneous baroreflex sensitivity induced by 60 days of head-down bed rest. However, this countermeasure had very little effect on cardiac hemodynamics and did not improve the orthostatic tolerance. This combined countermeasure did not efficiently prevent orthostatic intolerance but prevents changes in the autonomic nervous system associated with cardiovascular deconditioning. The underlying mechanisms remain hypothetical but might involve cutaneous and muscular mechanoreceptors.     

Integrative control of the skeletal muscle microcirculation in the maintenance of arterial pressure during exercise.

Skeletal muscle blood flow and vascular conductance are influenced by numerous factors that can be divided into two general categories: central cardiovascular control mechanisms and local vascular control mechanisms. Central cardiovascular control mechanisms are thought to be designed primarily for the maintenance of arterial pressure and central cardiovascular homeostasis, whereas local vascular control mechanisms are thought to be designed primarily for the maintenance of muscle homeostasis. To support the high metabolic rates that can be generated during muscle contraction, skeletal muscle has a tremendous capacity to vasodilate and increase oxygen and nutrient delivery. During whole body dynamic exercise at maximal oxygen consumption (VO2 max), the skeletal muscle receives 85-90% of cardiac output. Yet despite receiving such a large fraction of cardiac output during high-intensity exercise, a vasodilator reserve remains with the potential to produce further elevations in skeletal muscle vascular conductance and blood flow. However, because maximal cardiac output is reached during exercise at VO2 max, further elevations in muscle vascular conductance would produce a fall in arterial pressure. Therefore, limits on muscle perfusion must be imposed during whole body exercise to prevent such drops in pressure. Effective arterial pressure control in response to a potentially hypotensive challenge during high-intensity exercise occurs primarily through reflex-mediated increases in sympathetic nerve activity, which are capable of modulating vasomotor tone of the skeletal muscle resistance vasculature. Thus skeletal muscle vascular conductance and perfusion are primarily mediated by local factors at rest and during exercise, but other centrally mediated control systems are superimposed on the dominant local control mechanisms to provide an integrated regulation of both arterial pressure and skeletal muscle vascular conductance and perfusion during whole body dynamic exercise.     

(In)activity-dependent alterations in resting and reflex control of splanchnic sympathetic nerve activity

The negative effects of sympathetic overactivity on long-term cardiovascular health are becoming increasingly clear. Moreover, recent work done in animal models of cardiovascular disease suggests that sympathetic tone to the splanchnic vasculature may play an important role in the development and maintenance of these disease states. Work from our laboratory and others led us to hypothesize that a lack of chronic physical activity increases resting and reflex-mediated splanchnic sympathetic nerve activity, possibly through changes occurring in a key brain stem center involved in sympathetic regulation, the rostral ventrolateral medulla (RVLM). To address this hypothesis, we recorded mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SSNA) in a group of active and sedentary animals that had been housed for 10-13 wk with or without running wheels, respectively. In experiments performed under Inactin anesthesia, we tested responses to RVLM microinjections of glutamate, responses to baroreceptor unloading, and vascular reactivity, the latter of which was performed under conditions of autonomic blockade. Sedentary animals exhibited enhanced resting SSNA and MAP, augmented increases in SSNA to RVLM activation and baroreceptor unloading, and enhanced vascular reactivity to α(1)-receptor mediated vasoconstriction. Our results suggest that a sedentary lifestyle increases the risk of cardiovascular disease by augmenting resting and reflex-mediated sympathetic output to the splanchnic circulation and also by increasing vascular sensitivity to adrenergic stimulation. We speculate that regular physical exercise offsets or reverses the progression of these disease processes via similar or disparate mechanisms and warrant further examination into physical (in)activity-induced sympathetic nervous system plasticity.     

Impact of exercise training on cardiovascular disease and risk

Epidemiological studies in large cohorts support the notion that physical fitness is associated with reduced cardiovascular mortality and hospitalization due to cardiovascular disease. During the last 20 years even the concept of resting inactive after a myocardial infarction has dramatically changed and nowadays patients are mobilized and included into exercise training programs very shortly after the insult. Unfortunately, these beneficial effects of exercise training are independent of the genetic background and are only observed in case the training program is not paused for a longer time. Therefore, to take advantage of the effects of exercise training in health care the challenge for the future is to increase exercise compliance by offering interesting and effective exercise training programs. At the physiological and molecular level, exercise training affects several organs like the vascular system and the skeletal muscle. Changes elicited by regular exercise training range in the vascular system from increasing vasodilation due to an elevation of bioavailable nitric oxide to a shift in the catabolic/anabolic balance in the peripheral skeletal muscle. In this review we discuss the healthy benefit of exercise training and the molecular changes triggered by exercise training in the setting of secondary prevention.     

Endocannabinoids and liver disease. V. endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis

Cirrhosis is associated with marked cardiovascular disturbances. These include hyperdynamic circulation characterized by reduced peripheral vascular resistance and mean arterial pressure and increased cardiac output. Despite the baseline increase in cardiac output, ventricular responsiveness to stimuli is blunted. A number of cellular signaling pathways have been shown to contribute to these abnormalities, including central nervous system cardiovascular dysregulation and humoral factors such as nitric oxide. Endogenous and exogenous cannabinoids have significant cardiovascular effects. Recent evidence suggests that increased activity of the endocannabinoid system at multiple levels contributes to development of both cardiac and vascular changes in cirrhosis. This brief review surveys recent in vivo and in vitro findings in an attempt to highlight the areas of agreement and areas of controversy in the field. The endocannabinoid system affects key cardiovascular regulators, including the autonomic nervous system, cardiac muscle, and vascular smooth muscle. The interplay among these modes of action further complicates interpretation of the in vivo findings. The broad range of cardiovascular actions of endocannabinoids provides ample opportunities for pharmacological manipulation. At the same time, it increases the possibility of undesirable side effects, which need to be carefully evaluated in long-term studies.     

Electrodermal and cardiovascular manifestations of emotions in children

The purpose of this paper is to analyze the current state of developmental researches in the area of psychophysiology of emotions in preschool and elementary school children. Electrodermal and cardiovascular activity measures are considered as the sources of indices of the autonomic nervous system activation during emotion-eliciting stimulation in children. We discuss the question of sensitivity of phasic and tonic autonomic measures for the identification of occurrence of emotion, mapping it along with valence and arousal dimensions in affective space, and to further differentiate emotions by their physiological manifestations. Considered are the conceptual and methodological issues related to psychophysiological measurements and developmental factors affecting the emotional reactivity in children. Special attention is devoted to the developmental aspects of psychophysiological studies on emotion such as the maturation of organs, integration of the autonomic and central nervous systems, age and gender-related changes in autonomic reactivity, and development of inhibitory control. Summarized are main findings relevant to psychophysiology of emotions in preschool and early school-age children and suggested are most perspective directions of their integration in the framework of modern theories of emotion.     

Influence of moderate physical exercise on the cardiac rhythm parameters of elementary and junior high school children

To reveal the specific features of the influence of moderate exercise (running) on the autonomic regulation of the cardiac rhythm, changes in the heart rate variability (HRV) parameters have been analyzed during three months in 292 children aged 9–14, as dependent on the sex and the baseline autonomic tone estimated by means of cluster analysis. It has been shown that, in schoolchildren engaged in running for health, HRV changes give evidence for the optimization of the mechanisms of autonomic regulation. The HRV parameters in the girls were more resistant to muscular activity compared to boys. The data obtained indicate that running for health requires a differential approach to dosing of the exercise, taking into account the sex and the baseline autonomic tone.     

Gadolinium does not blunt the cardiovascular responses at the onset of voluntary static exercise in cats: a predominant role of central command

The cardiovascular adaptation at the onset of voluntary static exercise is controlled by the autonomic nervous system. Two neural mechanisms are responsible for the cardiovascular adaptation: one is central command descending from higher brain centers, and the other is a muscle mechanosensitive reflex from activation of mechanoreceptors in the contracting muscles. To examine which mechanism played a major role in producing the initial cardiovascular adaptation during static exercise, we studied the effect of intravenous administration of gadolinium (55 micromol/kg), a blocker of stretch-activated ion channels, on the increases in heart rate (HR) and mean arterial blood pressure (MAP) at the onset of voluntary static exercise (pressing a bar with a forelimb) in conscious cats. HR increased by 31 +/- 5 beats/min and MAP increased by 15 +/- 1 mmHg at the onset of voluntary static exercise. Gadolinium affected neither the baseline values nor the initial increases of HR and MAP at the onset of exercise, although the peak force applied to the bar tended to decrease to 65% of the control value before gadolinium. Furthermore, we examined the effect of gadolinium on the reflex responses in HR and MAP (18 +/- 7 beats/min and 30 +/- 6 mmHg, respectively) during passive mechanical stretch of a forelimb or hindlimb in anesthetized cats. Gadolinium significantly blunted the passive stretch-induced increases in HR and MAP, suggesting that gadolinium blocks the stretch-activated ion channels and thereby attenuates the reflex cardiovascular responses to passive mechanical stretch of a limb. We conclude that the initial cardiovascular adaptation at the onset of voluntary static exercise is predominantly induced by feedforward control of central command descending from higher brain centers but not by a muscle mechanoreflex.     

A Bond Graph Model of the Cardiovascular System

The study of the autonomic nervous system (ANS) function has shown to provide useful indicators for risk stratification and early detection on a variety of cardiovascular pathologies. However, data gathered during different tests of the ANS are difficult to analyse, mainly due to the complex mechanisms involved in the autonomic regulation of the cardiovascular system (CVS). Although model-based analysis of ANS data has been already proposed as a way to cope with this complexity, only a few models coupling the main elements involved have been presented in the literature. In this paper, a new model of the CVS, representing the ventricles, the circulatory system and the regulation of the CVS activity by the ANS, is presented. The models of the vascular system and the ventricular activity have been developed using the Bond Graph formalism, as it proposes a unified representation for all energetic domains, facilitating the integration of mechanic and hydraulic phenomena. In order to take into account the electro-mechanical behaviour of both ventricles, an electrophysiologic model of the cardiac action potential, represented by a set of ordinary differential equations, has been integrated. The short-term ANS regulation of heart rate, cardiac contractility and peripheral vasoconstriction is represented by means of continuous transfer functions. These models, represented in different continuous formalisms, are coupled by using a multi-formalism simulation library. Results are presented for two different autonomic tests, namely the Tilt Test and the Valsalva Manoeuvre, by comparing real and simulated signals.