Cardiovascular re-adjustments and baroreflex response during clinical reambulation procedure at the end of 35-day bed rest in humans.

During the reambulation procedure after 35-day head-down tilt bed rest (HDTBR) for 9 men, we recorded for the first time heart rate (HR; with electrocardiogram) and arterial pressure profiles (fingertip plethysmography) for 5 min in HDTBR and horizontal (SUP) positions, followed by 12 min in standing position, during which 4 subjects fainted (intolerant, INT) and were laid horizontal again (Recovery). We computed: mean arterial pressure (P̄; pressure profiles integral mean), stroke volume (SV; obtained with Modelflow method), and cardiac output (Q̇; SV × HR). All cardiovascular data remained stable in HDTBR and SUP for both groups (EXP). Taking the upright posture, EXP showed a decrease in SV and an increase in HR, becoming significantly different from SUP within 1 min. Further evolution of these parameters kept Q̇ stable in both groups until the second minute of standing. Afterward, in INT, P̄ precipitated without further HR increases: SV stopped being corrected and Q̇ reached 2.9 ± 0.4 L·min(-1) at the last 15 s of standing. Sudden drop in P̄ allowed identification of a low-pressure threshold in INT (70.7 ± 12.9 mm Hg), after which syncope occurred within 80 s. During Recovery, baroreflex curves showed a flat phase (P̄ increase, HR stable), followed by a steep phase (P̄ increased, HR decreased, starting when P̄ was 84.5 ± 12.5 mm Hg and Q̇ was 9.6 ± 1.5 L·min(-1)). INT, in contrast with tolerant subjects, did not sustain standing because HR was unable to correct for the P̄ drop. These results indicate a major role for impaired arterial baroreflexes in the onset of orthostatic intolerance.

Cardiovascular determinants of maximal oxygen consumption in upright and supine posture at the end of prolonged bed rest in humans.

We tested the hypothesis that, after bed rest, maximal oxygen consumption ( VO2max ) decreases more upright than supine, because of adequate cardiovascular response supine, but not upright. On 9 subjects, we determined VO2max and maximal cardiac output (Q ) upright and supine, before and after (reambulation day upright, the following day supine) 35-day bed rest, by classical steady state protocol. Oxygen consumption, heart rate (f(H)) and stroke volume (Q(st)) were measured by a metabolic cart, electrocardiography and Modelflow from pulse pressure profiles, respectively. We computed Q as f(H) times Q(st), and systemic oxygen flow ( QaO2) as Q. times arterial oxygen concentration, obtained after haemoglobin and arterial oxygen saturation measurements. Before bed rest, all parameters at maximal exercise were similar upright and supine. After bed rest, VO2max was lower (p<0.05) than before, both upright (-38.6%) and supine (-17.0%), being 30.8% higher supine than upright. Maximal Q(st) decreased upright (-44.3%), but not supine (+3.7%), being 98.9% higher supine than upright. Maximal Q decreased upright (-45.1%), but not supine (+9.0%), being higher supine than upright (+98.4%). Maximal QaO2 decreased upright (-37.8%), but not supine (+14.8%), being higher (+74.8%) upright than supine. After bed rest, the cardiovascular response (i) did not affect VO2max supine, (ii) partially explained the VO2max decrease upright, and (iii) caused the VO2max differences between postures. We speculate that impaired peripheral oxygen transfer and/or utilisation may explain the VO2max decrease supine and the fraction of VO2max decrease upright unexplained by cardiovascular responses.

Time-independent indices of circadian blood pressure and heart rate regulation from ambulatory blood pressure monitoring.

OBJECTIVES: We hypothesized that addressing the 24-h relationship between RR interval and systolic arterial pressure (SAP) during ambulatory blood pressure monitoring could detect alterations in circadian arterial pressure and heart rate profile and could also be linked to the ambulatory arterial stiffness index. METHODS: We analyzed retrospectively 676 ambulatory blood pressure monitoring 24-h recordings. Individuals were median split into low (n = 338) and high (n = 338) SAP groups (mean 24 h of 120 +/- 7, 140 +/- 10 mmHg, respectively). We estimated for each individual ambulatory blood pressure monitoring, the slope (ms/mmHg) of the regression of RR interval on SAP over 24-h (defined as theta index). RESULTS: Theta index was significantly (P < 0.001) steeper in individuals with lower pressure than those with higher pressure, whereas day-night difference in SAP did not differ significantly. Theta index was also less negative in nondipper than in dipper individuals and displayed a significant interaction (P < 0.001) with hypertension. The theta index correlated significantly with age and ambulatory arterial stiffness index. Moreover, approximately 14-month reproducibility, as assessed by intraclass correlation coefficient, for theta index was similar to SAP (0.703 and 0.757, respectively). CONCLUSION: These results indicate that theta can detect differences in circadian arterial pressure profile that could assess the efficiency of arterial pressure (and heart rate) regulatory mechanisms over the whole day in individuals with different arterial pressure levels. Theta can be easily obtained under ambulatory conditions without any assumption on underlying mathematical models or operator-dependent attribution of arterial pressure and heart rate values to daytime or night-time subperiods. Cross-sectional and prospective studies relating theta to target organ damage and cardiovascular outcomes will inform us about its clinical relevance.

Baroreflex and metaboreflex control of cardiovascular system during exercise in space.

This brief review summarizes current knowledge on the neural mechanisms of cardiovascular regulation during exercise in space, with specific emphasis on the role of the arterial baroreflex and the muscle metaboreflex, with the attendant modifications in autonomic nervous system activity, in determining the cardiovascular responses to exercise in microgravity conditions. Available data suggest that the muscle metaboreflex is enhanced during dynamic exercise in space and that the potentiation of the muscle metaboreflex affects the vagally mediated arterial baroreflex contribution to HR control.

Prolonged head down bed rest-induced inactivity impairs tonic autonomic regulation while sparing oscillatory cardiovascular rhythms in healthy humans.

BACKGROUND: Physical inactivity represents a major risk for cardiovascular disorders, such as hypertension, myocardial infarction or sudden death; however, underlying mechanisms are not clearly elucidated. Clinical and epidemiological investigations suggest, beyond molecular changes, the possibility of an induced impairment in autonomic cardiovascular regulation. However, this hypothesis has not been tested directly. METHODS: Accordingly, we planned a study with noninvasive, minimally intrusive, techniques on healthy volunteers. Participants were maintained for 90 days strictly in bed, 24 h a day, in head-down (-6 degrees ) position (HDBR). Physical activity was thus virtually abolished for the entire period of HDBR. We examined efferent muscle sympathetic nerve activity, as a measure of vascular sympathetic control, baroreceptor reflex sensitivity, heart rate variability (assessing cardiovagal regulation), RR and systolic arterial pressure and low-frequency and high-frequency normalized components (as a window on central oscillatory regulation). Measures were obtained at rest and during simple maneuvers (moderate handgrip, lower body negative pressure and active standing) to assess potential changes in autonomic cardiovascular responsiveness to standard stimuli and the related oscillatory profiles. RESULTS: HDBR transiently reduced muscle sympathetic nerve activity, RR, heart rate variability and baroreceptor reflex sensitivity late during HDBR or early during the recovery phase. Conversely, oscillatory profiles of RR and systolic arterial pressure variability were maintained throughout. Responsiveness to test stimuli was also largely maintained. CONCLUSION: Prolonged inactivity as induced by HDBR in healthy volunteers reduces both cardiovagal and vascular sympathetic regulation, while largely maintaining peripheral responsiveness to standardized stimuli and sparing the functional structure of central oscillatory cardiovascular regulation.

A point-to-point simple telehealth application for cardiovascular prevention: the ESINO LARIO experience. Cardiovascular prevention at point of care.

Recent epidemiological evidence indicates that chronic degenerative diseases, notably cardiovascular, represent the major toll in terms of death and of impaired quality of life. Recent estimates indicate that a small increase in financial resources in a number of clinical cases may be sufficient to minimize the consequences of elevated cardiovascular risk per individual. The observation that lifestyle choices, and in particular increased physical exercise, might strongly impact cardiovascular risk, suggests a redesign of preventive strategies, based on the combination of pharmacological and behavioral interventions. Following our recent experience with the INteractive teleConsultation network for worldwide healthcAre Services (INCAS) system, we designed a simpler point-to-point telehealth infrastructure, to be employed in cardiovascular risk reduction programs, predicting a high level of acceptance from the population, at the cost of very limited investment. This model was tested on 181 subjects (ages 18-80 years) in the Italian mountain village of Esino Lario. These subjects underwent a screening test to evaluate arrhythmia and cardiometabolic risks (arrhythmias were found in 14% of subjects, systolic arterial pressure was observed in 43% of subjects above 140 mm Hg, diastolic arterial pressure in 31% above 90 mm Hg). This study demonstrates the feasibility of a scaled-down telehealth application particularly suited to cardiovascular prevention in remote areas, such as in mountain villages.

Hemodynamic, autonomic and baroreflex changes after one night sleep deprivation in healthy volunteers.

BACKGROUND: Sleep disorders are associated to a number of cardiovascular disturbances that might increase cardiovascular risk. Sleep deprivation, in particular, might, by inducing autonomic dysregulation, raise arterial pressure and hypertensive risk. Available evidence however is contradictory. METHODS: We tested the main hypothesis that one night sleep deprivation in 24 volunteers might alter hemodynamics (heart rate and Arterial Pressure - AP), autonomic regulation (mono and bivariate spectral analysis of RR and non invasive AP variability) and baroreflex control (spectral index alpha and spontaneous baroreflex slope), performance indices (reaction time) and subjective stress (questionnaires and salivary cortisol). Volunteers were studied in normal living conditions and while kept in isolation and confinement, to test the presence of possible bias related to environmental stress. RESULTS: Results indicate that there were no differences between normal living conditions and isolation and confinement (Intraclass Correlation Coefficient >0.75 for most variables). Conversely, after one night sleep deprivation subjects felt tired (p<0.05), and performance deteriorated (p<0.05), while cortisol profile was substantially maintained, hemodynamic parameters did not change and HRV and index alpha increased slightly. CONCLUSIONS: Findings support the contention that one night sleep deprivation, in absence of significant additional stress or disturbances, does not lead to increased arterial pressure values or to changes in autonomic or baroreflex profiles that could conceivably favor hypertension development, but induces the expected increase in tiredness and reduction in performance.

Evidence of autonomic dysregulation in otherwise healthy cancer caregivers: a possible link with health hazard.

Caregiving, an important component of cancer patient treatment, may set forth a cascade of stress responses such as sympatho-adrenal activation, immuno-humoral changes and an unhealthy lifestyle, which could be hazardous to caregivers' health. In this observational study, we addressed whether autonomic nervous system (ANS) regulation and perception of stress would be altered in a group of 58 health cancer caregivers as compared to 60 controls. We employed non invasive autoregressive spectral analysis of cardiovascular variabilities and ad hoc questionnaires. Caregivers show, in addition to signs of psychological involvement, a clear autonomic imbalance, suggestive of sympathetic predominance at rest and of a reduction of vagal cardiac regulation (overall gain of baroreflex -index alpha- was respectively of 17.5+/-1.5 versus 25.1+/-1.8 msec/mmHg, p<<0.02). These data suggest possible preventive strategies, based on tailored treatments aiming at a betterment of individual autonomic profile.

Feasibility of assessing autonomic dysregulation at a distance: the case of the HIV-positive patient.

Alterations in lipid metabolism are a possible consequence of highly active antiretroviral therapies (HAART) for human immunodeficiency virus (HIV)-positive patients with consequent increase of cardiovascular risk. In this context we hypothesized that both acquired immunodeficiency syndrome (AIDS) and HAART might be associated to alterations in autonomic cardiovascular regulation. In this preliminary investigation we enrolled a total of 66 men, subdivided in two groups, 33 HIV-positive patients, and 33 healthy controls, and we tested the hypothesis that heart rate variability (HRV) of HIV positive patients can be assessed with a transtelephonic approach from the HIV clinic: 100% of the total of electrocardiograms (ECG) recordings that were sent from the distant site were successfully received and analyzed. Evaluation of the signal was subsequently performed in the centralized laboratory, and consisted in extracting the RR interval variability (RRV) series and afterward subjecting it to autoregressive spectral analysis. This study shows the feasibility of obtaining, from personnel without specific training, adequate RR variability data for further spectral analysis form a distant specialized autonomic laboratory. This feature is of critical importance in the context of possible large-scale application of this simple telemedicine approach.

Stress management at the worksite: reversal of symptoms profile and cardiovascular dysregulation.

Work stress may increase cardiovascular risk either indirectly, by inducing unhealthy life styles, or directly, by affecting the autonomic nervous system and arterial pressure. We hypothesized that, before any apparent sign of disease, work-related stress is already accompanied by alterations of RR variability profile and that a simple onsite stress management program based on cognitive restructuring and relaxation training could reduce the level of stress symptoms, revert stress-related autonomic nervous system dysregulation, and lower arterial pressure. We compared 91 white-collar workers, enrolled at a time of work downsizing (hence, in a stress condition), with 79 healthy control subjects. Psychological profiles were assessed by questionnaires and autonomic nervous system regulation by spectral analysis of RR variability. We also tested a simple onsite stress management program (cognitive restructuring and relaxation training) in a subgroup of workers compared with a sham subgroup (sham program). Workers presented an elevated level of stress-related symptoms and an altered variability profile as compared with control subjects (low-frequency component of RR variability was, respectively, 65.2+/-2 versus 55.3+/-2 normalized units; P<0.001; opposite changes were observed for the high-frequency component). These alterations were largely reverted (low-frequency component of RR variability from 63.6+/-3.9 to 49.3+/-3 normalized units; P<0.001) by the stress management program, which also slightly lowered systolic arterial pressure. No changes were observed in the sham program group. This noninvasive study indicates that work stress is associated with unpleasant symptoms and with an altered autonomic profile and suggests that a stress management program could be implemented at the worksite, with possible preventive advantages for hypertension.

Muscle metaboreflex contribution to cardiovascular regulation during dynamic exercise in microgravity: insights from mission STS-107 of the space shuttle Columbia.

One of the most important features of prolonged weightlessness is a progressive impairment of muscular function with a consequent decrease in exercise capacity. We tested the hypothesis that the impairment in musculo-skeletal function that occurs in microgravity results in a potentiation of the muscle metaboreflex mechanism and also affects baroreflex modulation of heart rate (HR) during exercise. Four astronauts participating in the 16 day Columbia shuttle mission (STS-107) were studied 72-71 days before launch and on days 12-13 in-flight. The protocol consisted of 6 min bicycle exercise at 50% of individual V(o2,max) followed by 4 min of postexercise leg circulatory occlusion (PECO). At rest, systolic (S) and diastolic (D) blood pressure (BP), R-R interval and baroreflex sensitivity (BRS) did not differ significantly between pre- and in-flight measurements. Both pre- and in-flight, SBP increased and R-R interval and BRS decreased during exercise, whereas DBP did not change. During PECO preflight, SBP and DBP were higher than at rest, whereas R-R interval and BRS recovered to resting levels. During PECO in-flight, SBP and DBP were significantly higher whereas R-R interval and BRS remained significantly lower than at rest. The part of the SBP response (delta) that was maintained by PECO was significantly greater during spaceflight than before (34.5 +/- 8.8 versus 13.8 +/- 11.9 mmHg, P = 0.03). The tachycardic response to PECO was also significantly greater during spaceflight than preflight (-141.5 +/- 25.2 versus - 90.5 +/- 33.3 ms, P = 0.02). This study suggests that the muscle metaboreflex is enhanced during dynamic exercise in space and that the potentiation of the muscle metaboreflex affects the vagally mediated arterial baroreflex contribution to HR control.

Preliminary experience of shared clinical management between Milan and Pointe Noire using the INteractive TeleConsultation Network for Worldwide HealthcAre Services (INCAS): telemedicine between Milan and Africa.

This paper describes preliminary experience in shared clinical management of patients located in Pointe Noire, Africa, and a referral center, Sacco University Hospital, located in Milan, Italy. The employed infrastructure INteractive TeleConsultation Network for Worldwide HealthcAre Services (INCAS) jointly developed by CEFRIEL (Center of Excellence For Research, Innovation, Education & Industrial Labs partnership) and ENI (Ente Nazionale Idrocarburi) is based on commercial off-the-shelf technology. This minimizes maintenance problems, while permitting a simple and friendly sharing of data using the telephone and e-mail for store-and-forward applications. The critical aspect of the flow of events comprising the exchange of information is discussed. In 60% of cases, only one telemedicine consultation was required. In the remainder 40%, a number of telemedicine consultations were required for appropriate management of clinical cases. The project demonstrated flexibility as documented by the wide range of pathologies that can be dealt with it. Finally the possibility of using shared clinical management as a learning tool is highlighted by the steep and rising learning curve. We conclude, however, that the patient, although handled in a "virtual" manner, should be viewed as very "real," as some of them elected to close the gap physically between Pointe Noire and Milan, and chose to be treated at the referral site.