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Biomedical subjects

Massimo Pagani

Publications and source records attributed to Massimo Pagani.

At least 19 recordsLinked to original sources

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.

Adult↗

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.

Adaptation, Physiological↗

Is reduced baroreflex gain a component of the metabolic syndrome? Insights from the LINOSA study.

OBJECTIVE: To assess the relationship between insulin resistance and baroreflex gain (BRS) in the context of the metabolic syndrome. DESIGN: Observational population study. PATIENTS: We studied the healthy population of a small Mediterranean island (Linosa, about 0.5 square miles, 450 inhabitants) where genetic, psychosocial and behavioral bias is likely to be minimal for historical and social reasons. MEASURES: Baroreflex gain (BRS, by the frequency domain alpha index) and indices of autonomic regulation of the sino-atrial (SA) node derived from spectral analysis of RR interval variability were obtained, together with metabolic and behavioral indicators in the 144 participating subjects (age range 20-82 years). Carotid artery thickness (CCA) was also obtained with computer-aided ultrasound techniques. Insulin resistance was estimated by the homeostasis model assessment (HOMA), and subjects divided in tertiles accordingly. RESULTS: BRS appeared to be reduced progressively with increasing levels of HOMA (respectively, 21.0 +/- 2.6, 17.7 +/- 1.7, 15.7 +/- 1.9 ms/mmHg, P < 0.03), while spectral indices of autonomic SA regulation appeared to be only insignificantly affected. Conversely, CCA was significantly increased with increasing HOMA (P < 0.024). Furthermore, BRS appeared to be significantly correlated with various elements of the metabolic syndrome, with CCA and abdominal obesity showing the strongest link. CONCLUSIONS: In an otherwise healthy population, BRS, but not spectrally derived indices of SA node autonomic regulation, are progressively reduced with increasing severity of insulin resistance, possibly as a consequence of attendant carotid artery thickening.

Adult↗

Coupling arterial windkessel with peripheral vasomotion: modeling the effects on low-frequency oscillations.

Arterial pressure (AP) and heart rate (HR) waves have long been recognized as an important sign of cardiovascular regulation, however, the underlying interactions involving vasomotion, arterial mechanisms and neural regulation have not been clarified. With the aid of simple dynamical models consisting of active peripheral vascular districts (PVDs) fed by a compliant/resistant arterial tree, the relationship between local AP and flow and systemic AP waves were analyzed. A PVD was described as a nonlinear flow regulation loop. Various feedback dynamics were experimented and general properties were focused. The PVDs displayed a region of active flow compensation against pressure changes, in which self-sustained low-frequency (LF, 0.1 Hz) appeared. Oscillations critically depended on parameter, Teq, analogous to a windkessel time constant, proportional to arterial compliances: a value of about 2 s (consistent with a normal pulse pressure) performed a buffering effect essential for LF oscillations in peripheral flow; conversely, stiffer arteries damped LF vasomotion. Two PVDs fed by a common compliance oscillated in phase opposition; the consequent negative interference cancelled systemic AP waves, even in presence of large peripheral oscillations. The partial disruption of phase opposition by a common neural drive oscillating at a LF proximal to that of the PVDs unveiled LF waves in AP. Also, several PVDs with randomly different natural frequencies displayed a tendency to reciprocal cancellation, while a limited neurally induced phase alignment unmasked LF oscillations at systemic level. It is concluded that vasomotion, arterial compliances and, neural drives are all elements which may cooperate in forming AP waves.

Animals↗

Impact of chronic psychosocial stress on autonomic cardiovascular regulation in otherwise healthy subjects.

Elevated psychosocial stress might favor the occurrence of cardiovascular disease; however, mechanisms are incompletely understood. We hypothesized that patients (n=126; 44+/-1 years of age) referred to an internal medicine clinic because of symptoms related to chronic psychosocial stress would demonstrate signs of autonomic dysregulation compared with controls (n=132; 42+/-1 years of age). We used autoregressive spectral analysis of RR interval variability to obtain indirect markers of sympathetic and of vagal (respectively, low-frequency and high-frequency components, both expressed in normalized units) oscillatory modulation of sinoatrial node, as well as of sympathetic vasomotor regulation (low-frequency component of systolic arterial pressure variability) and of cardiac baroreflex sensitivity (alpha-index). Higher values of systolic and diastolic arterial pressure (respectively, 124+/-1 versus 117+/-1 mm Hg and 80+/-1 versus 75+/-1 mm Hg; both P<0.001), altered markers of autonomic regulation (increased normalized low-frequency and reduced high-frequency component of RR variability, P<0.005; increased-low frequency component of systolic arterial pressure variability, P<0.002), and reduced baroreflex sensitivity (19.3+/-1.4 versus 23.0+/-2.0 ms/mm Hg; P<0.05) were observed in patients compared with controls. Autonomic responses to active standing were also blunted in stressed patients. Autonomic markers were significantly correlated to stress perception score and were capable of discriminating between controls and patients with a high degree of accuracy. Chronic real-life stress in humans appears associated to increased arterial pressure and to impaired autonomic regulation of cardiovascular functions. The combination of sympathetic predominance, vagal withdrawal, and blunted baroreflex sensitivity might represent a treatable mechanistic link between psychosocial factors and future incidence of hypertension.

Adult↗

Selective reductions of cardiac autonomic responses to light bicycle exercise with aging in healthy humans.

We examined on 56 (age 38+/-2 [range: 16-60] years) healthy subjects the effects of aging on cardiovascular autonomic responses to progressive supine bicycle exercise of light intensity. Autoregressive spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided measures of the exercise-induced changes in baroreflex gain (by index alpha) and in sympathetic and vagal modulation of the SA node (by the normalized low [LF] and high frequency [HF] component of RR interval variability, respectively), as well as of changes in sympathetic vasomotor control (LF(SAP)). For each hemodynamic and autonomic variable, the gain of the response was expressed both as individual step increments, and as the slope of the linear regression of the sequential data points from rest and during the three steps of exercise. Age resulted significantly correlated to changes in spectral derived markers of SA modulation (LF(RR), HF(RR) and index alpha). Conversely, no significant relationships were found with changes in RR interval, in SAP and indices of vascular regulation (LF(SAP)). In addition, exercise-induced changes in indices of SA node regulation were more evident in the youngest tertile (age 25+/-1 years), compared to the oldest tertile (age 52+/-1 years). In conclusion, we have observed that aging progressively and selectively reduces the cardiac autonomic excitatory response to light exercise, while hemodynamic and vascular responsiveness are maintained.

Adolescent↗

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.

Congo↗

Contrasting effects of acute and chronic cigarette smoking on skin microcirculation in young healthy subjects.

OBJECTIVE: The aim of our study was to assess the effects of acute and chronic smoking on skin microvascular properties of young healthy subjects. DESIGN: An observational study, using a totally non-invasive approach, employing continuous palmar microvascular flow (laser Doppler) and arterial pressure measurements, to compute estimates of microvascular resistive (Z0) and oscillatory (impedance, i.e. ZC) properties. Measures were obtained at baseline and after iontophoretic administration of acetylcholine (ACh), an endothelium-dependent vasodilator and of sodium nitroprusside (NP), an endothelium-independent vasodilator. PARTICIPANTS: A total of 20 healthy male subjects (nine habitual smokers and 11 non-smokers; aged 27 +/- 1 and 29 +/- 2 years, respectively) in resting conditions and during administration of ACh and of NP (in two different days), before and after smoking one cigarette were evaluated. RESULTS: Smokers showed significant lower baseline Z0 and ZC than non-smokers. In non-smokers, ACh and NP iontophoresis induced a significant decrease of both Z0 and ZC, before and after smoking one cigarette (P < 0.02). Conversely, in smokers, both Z0 and ZC were not affected by ACh iontophoresis before acute smoking, while, after smoking, a significant decrease of both Z0 and ZC (P < 0.02) was detected after ACh challenge. In smokers, both Z0 and ZC were not affected by NP iontophoresis, either before or after smoking a cigarette. CONCLUSIONS: Smokers appeared characterized by a complex disruption of peripheral microcirculatory regulation, including inappropriate resting vasodilation, impaired endothelium-dependent and independent vasodilation, paradoxical recovery of endothelium-dependent vasodilation in response to acute smoking.

Acetylcholine↗

Altered profile of baroreflex and autonomic responses to lower body negative pressure in chronic orthostatic intolerance.

BACKGROUND: Chronic orthostatic intolerance (COI) is a common and disabling autonomic syndrome of unclear pathophysiology. We tested the hypothesis that baroreflex and autonomic responses to graded lower body suction (LBNP, up to -40 mmHg) could be altered in COI patients. METHODS: Electrocardiogram (ECG), non-invasive arterial blood pressure and respiratory activity were measured during progressive LBNP (seven patients and seven volunteers). Lumped arterial baroreflex sensitivity (alpha index), and its arterial and cardiopulmonary components, were assessed by multivariate closed-loop analysis of RR interval and systolic arterial pressure (SAP) spontaneous variabilities and respiration. Monovariate spectral analysis of RR interval and SAP variability provided markers of autonomic regulation of the sinoatrial (SA) node and of vascular sympathetic modulation. RESULTS: Similar reductions in overall and cardiopulmonary baroreflex gain were observed in both groups in response to graded LBNP. In contrast, only controls demonstrated a selective increase in arterial baroreflex sensitivity, at low-grade LBNP. Clear increases in the low-frequency component of RR interval variability (LFRR) [and decreases in the high-frequency component of RR interval variability (HFRR), both in normalized units] were observed in controls with graded LBNP, while insignificant changes occurred in COI patients, who showed, conversely, exaggerated sympathetic vasomotor responses [as assessed by the low frequency component of SAP variability (LFSAP)]. CONCLUSIONS: Patients with chronic orthostatic intolerance show distinct signs of altered baroreflex and autonomic regulation of the SA node and of the vasculature in response to graded LBNP.

Adult↗

T-wave and heart rate variability changes to assess training in world-class athletes.

PURPOSE: A decrease of electrocardiographic T-wave voltage with increasing training loads has been reported in elite endurance athletes and ascribed to training-related adaptation in sympathetic activity to the ventricles. A switch from vagal to sympathetic predominance in sino-atrial node regulation on going from low to peak training load has been reported in world-class rowers. In this study on world-class endurance athletes, we tested the hypothesis that training-induced variations in T-wave amplitude at higher training loads are paralleled by changes in HR spectral profile. METHODS: We studied eight male rowers of the Italian national team in the season culminating with the Rowing World Championship. Athletes were evaluated at 50 and 100% of training load, approximately 20 d before the World Championship, and during the World Championship, when the intensity was markedly reduced. We assessed T-wave maximum amplitude in chest lead V6 and cardiac autonomic regulation by power spectral analysis of R-R interval variability. RESULTS: The increase in training load from 50 to 100% was accompanied by a significant decrease in high frequency and a significant increase in low-frequency R-R variability (in normalized units) with a concomitant significant decrease in T-wave amplitude (microV). Reduction in training load during the World Championship resulted in a return of spectral profile to the level observed at 50% training load and in a partial recovery of T-wave amplitude. HR did not change significantly. CONCLUSIONS: In high-performance world-class athletes, training load simultaneously affects both ventricular repolarization and HR variability patterns possibly through variations in cardiac sympathetic modulation to the ventricles and the sino-atrial node. Information on concomitant changes in ventricular repolarization and autonomic cardiac regulation might be employed to tailor training protocols of elite athletes.

Adult↗

Assessing autonomic disturbances of hypertension in the general practitioner's office: a transtelephonic approach to spectral analysis of heart rate variability.

OBJECTIVES: Spectral analysis of heart rate variability (HRV) provides potentially useful information on autonomic disturbances of human hypertension. However, its practical use outside the clinical laboratory is largely unexplored. The aim of this study was to test the feasibility of assessing HRV from the general practitioner's (GP's) office, using a novel transtelephonic approach. DESIGN: Parallel study on two similar groups: 150 subjects (100 hypertensives and 50 normotensives) studied in our hospital clinic and compared with 150 subjects studied in an out-of-hospital practice (100 hypertensive subjects from GPs' surgeries and 50 normotensive subjects participating in a multinational company's health maintenance programme). METHODS: Spectral analysis of RR interval variability was used to assess autonomic regulation of the sino-atrial (SA) node, both at rest and during standing. For the out-of-hospital practice, strings of continuous electrocardiograms (ECGs), recorded with a microminiature instrument, were fed, off line, through standard telephone lines to our laboratory for subsequent spectral analysis. RESULTS: RR spectral profiles obtained from healthy controls or hypertensive patients examined in their GPs' surgeries were similar to those obtained in a hospital clinic, both at rest and when standing up. CONCLUSIONS: The present study shows the feasibility of using a transtelephonic approach to perform spectral analysis of heart rate variability from physicians' surgeries. This method could favour a more widespread use of autonomic assessment in the clinical management of hypertension.

Adult↗

Impairment in cardiac autonomic regulation preceding arterial hypertension in humans: insights from spectral analysis of beat-by-beat cardiovascular variability.

BACKGROUND: Subjects in the upper-normal range of arterial pressure have an excess cardiovascular risk, which suggests that other factors, such as impaired autonomic regulation, might be implicated. This study was designed to assess whether noninvasive markers of cardiac and vascular autonomic regulation might already be altered in subjects with high-normal arterial pressure levels. METHODS AND RESULTS: We performed an observational study on a population comprising 300 subjects of both sexes with arterial pressure ranging from 90/60 to 210/120 mm Hg, who were divided into 3 groups (each n=100) with average systolic pressures of 103, 133, and 163 mm Hg. Autonomic regulation was inferred from spectral analysis of RR interval and systolic arterial pressure variability, considering rest and stand-induced changes, to account for sympathetic excitatory components. Significant alterations in markers of sinoatrial regulation (increased low-frequency normalized units, reduced high-frequency normalized units, and alpha-index) were already apparent in subjects in the second tertile, ie, those with arterial pressure within normal limits. Markers of vascular regulation instead showed significant alterations in the third (hypertensive) tertile. In response to standing, changes in markers of sinoatrial modulations were gradually reduced, whereas those of vascular regulation were increased. A tight link between progression of arterial pressure and the continuum of changes in autonomic markers as shown by simple correlation analysis appeared strongly affected by age and was spread across many spectral analysis-derived variables. Hypertensive autonomic dysregulation was particularly apparent in the youngest group. CONCLUSIONS: RR-variability parameters might prove useful to assess, with longitudinal studies, the mechanistic role of autonomic impairment in the increased risk of prehypertensive conditions.

Adolescent↗

Conversion from vagal to sympathetic predominance with strenuous training in high-performance world class athletes.

BACKGROUND: Benefits of moderate endurance training include increases in parasympathetic activity and baroreflex sensitivity (BRS) and a relative decrease in sympathetic tone. However, the effect of very intensive training load on neural cardiovascular regulation is not known. We tested the hypothesis that strenuous endurance training, like in high-performance athletes, would enhance sympathetic activation and reduce vagal inhibition. METHODS AND RESULTS: We studied the entire Italian junior national team of rowing (n=7) at increasing training loads up to 75% and 100% of maximum, the latter approximately 20 days before the Rowing World Championship. Autoregressive power spectral analysis was used to investigate RR interval and blood pressure (BP) variabilities. BRS was assessed by the sequences method. Increasing training load up to 75% of maximum was associated with a progressive resting bradycardia and increased indexes of cardiac vagal modulation and BRS. However, at 100% training load these effects were reversed, with increases in resting heart rate, diastolic BP, low-frequency RR interval, and BP variabilities and decreases in high-frequency RR variability and BRS. Three athletes later won medals in the World Championship. CONCLUSIONS: This study indicates that very intensive endurance training shifted the cardiovascular autonomic modulation from a parasympathetic toward a sympathetic predominance. This finding should be interpreted within the context of the substantial role played by the sympathetic nervous system in increasing cardiovascular performance at peak training. Whether the altered BP and autonomic function shown in this study might be in time hazardous to human cardiovascular system remains to be established.

Adult↗

Combined use of morphology discrimination, sudden onset, and stability as discriminating algorithms in single chamber cardioverter defibrillators.

Morphology Discrimination (MD) is a rhythm discriminator based on QRS morphology analysis that can be combined with other discriminators like Stability, with or without Sinus Interval History (SIH) and Sudden Onset. Thirty-five patients implanted with a St. Jude Medical single chamber ICD were evaluated during exercise testing, during induced AF, and during follow-up for 14 +/- 5 months. At exercise testing (60 episodes detected) MD had a specificity (SP) of 96.7% and Sudden Onset a SP of 91.7%; during induced AF (25 episodes) both MD and Stability had a SP of 96.0%. The diagnostic performance on spontaneous arrhythmias was as follows: for ventricular tachycardia (126 episodes) a sensitivity (SE) of 94.4% for MD, 92.1% for Sudden Onset, 89.7% for Stability without SIH and 79.4% for Stability + SIH; for sinus tachycardia (44 episodes) a SP of 86.4% for MD, 97.7% for Sudden Onset, 2.3% for Stability and of 95.5% for Stability + SIH. For AF (165 cases) a SP of 67.9% for MD, 69.1% for Stability and 90.3% for Stability + SIH, 44.8% for Sudden Onset. Use of MD alone provided a SE of 94.4% and a SP of 71.4% for spontaneous arrhythmias and combined use of the discriminators in a "2 of 3" diagnostic logic implied a SP of 90.9% with maintenance of 96.0% of SE. In single chamber ICDs a wide range of SE/SP ratios may be obtained by use of multiple discriminators, but use of the algorithm in a 2 of 3 diagnostic logic may achieve a SP of 90.9% and a SE of 96.0%.

Algorithms↗