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Biomedical subjects

D Lucini

Publications and source records attributed to D Lucini.

33 records · Page 2Linked to original sources

Cyclosporine-induced hypertension: evidence for maintained baroreflex circulatory control.

BACKGROUND: The clinical use of cyclosporine as an immunosuppressive agent enhanced long-term survival in transplant recipients at the expense of a high incidence of induced hypertension. Altered neurovegetative (autonomic) cardiovascular control is suspected as a mechanism of this form of hypertension. METHODS: Spectral analysis of systolic arterial pressure and R-R interval variability (electrocardiographic recordings) were performed, and the index alpha of baroreflex gain was computed in four groups of subjects matched for age: 13 orthotopic heart transplant recipients; 13 solid organ transplant recipients; 13 patients with essential hypertension; and 18 control subjects with normal blood pressure. All but the control subjects were treated with similar dihydropyridine calcium entry blockers. Heart and solid organ transplant recipients also received cyclosporine. RESULTS: R-R variance was lowest in the heart transplant recipients. The spectral profile of R-R interval was suggestive of sympathetic predominance in the patients with hypertension, but not in the solid organ transplant recipients or the control subjects. Systolic blood pressure variability and low frequency component (a marker of sympathetic vasomotor modulation) were similar in the four groups. The index alpha was 1.8 +/- 2.2 in heart transplant recipients, 11.7 +/- 6.6 in solid organ transplant recipients, 7.3 +/- 3.6 in patients with hypertension, and 13.5 +/- 6.4 msec/mm Hg in control subjects (p = 0.0001). CONCLUSIONS: These data indicate that (1) cyclosporine-induced hypertension in heart transplant recipients is associated with a loss of baroreflex function as a result of cardiac denervation-related uncoupling; (2) compared with patients with hypertension, organ transplant recipients with hypertension demonstrated a maintained baroreflex function as indicated by a lack of reduction of the index alpha; (3) baroreflex heart rate control in dihydropyridine-treated cyclosporine-induced hypertension is well maintained.

Adult↗

Effects of aging and of chronic obstructive pulmonary disease on RR interval variability.

Clinical and experimental investigations suggest that spectral analysis of RR interval variability might be employed to assess changes in autonomic regulation of the SA node occurring in various chronic, cardiac or respiratory conditions. We studied three groups of subjects: young healthy, older healthy, and old patients with chronic obstructive pulmonary disease (COPD), considering RR interval and breathing, i.e. tidal volume, variability in the frequency domain (AR algorithms), in order to obtain markers of the sympathetic and vagal modulation of the SA node [by way, respectively, of the low (LF) and high frequency (HF) spectral components]. The gain of the relationship between tidal volume and heart period variation (index beta) was also examined. COPD patients demonstrated a reduced resting RR variance with maintained spectral power distribution; upon tilting they did not manifest the usual increase of LF (and attendant decrease of HF) component. Additionally, we observed that the index beta at rest was significantly reduced in older as opposed to younger subjects. This index was also reduced by tilt, in both groups. In patients the index beta was reduced as compared to the group of similar age and younger subjects, and did not diminish further with tilt. This study indicates that in patients with COPD, sympathetic excitatory modulation of the SA node is depressed. Furthermore, the index beta, which provides an assessment of the gain of respiratory modulation of RR interval variability is significantly reduced in patients, as compared to healthy subjects of similar age. These abnormalities of autonomic control, may represent a functional correlation of the hyperinflated state present in this clinical condition which can be assessed non-invasively with spectral analysis of RR interval and respiration.

Adult↗

A controlled study of the autonomic changes produced by habitual cigarette smoking in healthy subjects.

OBJECTIVES: An increased sympathetic drive, in view of its proarrhythmic, proatherosclerotic, and prothrombotic actions, could contribute to the elevated cardiovascular risk of habitual smokers. However, the underlying mechanisms are still debated. In this study we address the hypothesis that spectral analysis of RR interval and systolic arterial pressure short-term variabilities may be used to assess the complex autonomic changes produced by habitual cigarette smoking. METHODS: A cross-sectional design compared heavy (> 20 cigarettes/day) habitual smokers (n = 20; 40 +/- 3 years), with similar age controls. Spectral analysis of RR interval variability provided markers of the sympatho-vagal balance modulating the SA node, by way of the normalised low frequency (LF approximately equal to 0.10 Hz) and high frequency (HF approximately equal to 0.25 Hz) components. The LF component of systolic arterial pressure (SAP) variability assessed the sympathetic vasomotor modulation. The frequency domain index (alpha) measured the baroreflex gain of the SA node. Subjects were studied at rest, and during the sympathetic excitation produced by active standing. RESULTS: In smokers LFRR was, at rest, greater than in controls (70.6 +/- 3.8 vs 46.0 +/- 2.5 normalised units, nu); concurrently HFRR was reduced (22.1 +/- 3.2 vs 42.0 +/- 2.8 nu). Baroreflex gain and RR variance were also smaller in smokers. LFSAP was, instead, similar in the smokers and control groups. The standing induced increase in LFRR was blunted (P < 0.001) in smokers. CONCLUSIONS: Spectral analysis of RR interval and systolic arterial pressure variability indicates that habitual cigarette smoking induces selective alterations in neural control of the SA node. An increase at rest in markers of sympathetic modulation is accompanied by signs of reduced vagal drive and depressed baroreflex gain; while sympathetic vasomotor modulation appears similar in controls and smokers. Data are consistent with the hypothesis that autonomic alterations may contribute to the increased cardiovascular risk present in smokers.

Adult↗

Analysis of initial autonomic adjustments to moderate exercise in humans.

OBJECTIVE: To determine whether signs of cardiac sympathetic activation (together with vagal withdrawal) can be observed in the autonomic balance modulating the sino-atrial node as early as the initial levels of a graded light dynamic exercise. PATIENTS AND METHODS: We studied 15 healthy ambulant subjects (mean +/- SD age 32 +/- 9 years; systolic/diastolic blood pressure 120 +/- 19/77 +/- 7 mmHg; heart rate 65 +/- 9 beats/min), who underwent a control recording of 10 min, followed by a three-step progressive (10, 20 and 30% of nominal maximum for age and sex) supine bicycle exercise. Spectral and cross-spectral analysis of RR and systolic arterial pressure variabilities were used to obtain non-invasive markers of the autonomic adjustments to exercise. RESULTS: The low-frequency component of RR interval variability (which, in normalized units, is a marker of sympathetic modulation of the sino-atrial (SA) node) was progressively increased during all three stages of bicycle exercise. No significant changes were observed in the low-frequency component of systolic arterial pressure variability (i.e. a marker of sympathetic drive to the vasculature) in the early stages of exercise, while a significant increase was observed at 30% of maximum. The index alpha (which provides a measure of the gain of the arterial pressure-heart period baroreflex) was progressively reduced during all three stages of exercise. CONCLUSIONS: While the sympathovagal balance modulating the SA node is immediately shifted towards sympathetic predominance (and vagal withdrawal), markers of peripheral vascular sympathetic activation appear increased only when 30% of maximum exercise is attained.

Adult↗

Sympathetic restraint of baroreflex control of heart period in normotensive and hypertensive subjects.

1. We assessed the effects of changing levels of sympathetic drive on the gain of baroreflex control of the sino-atrial node, in normotensive and hypertensive subjects. 2. Autoregressive spectral and cross-spectral analysis of R-R interval and systolic arterial pressure (non-invasive Finapres method) variabilities providing an estimate of baroreflex gain through the frequency domain index alpha were performed on data from 63 normotensive and 78 mild hypertensive subjects. Subjects were studied at rest and during active orthostatism, which induces sympathetic predominance. Seven control subjects and 14 hypertensive subjects were also studied after chronic atenolol treatment, to attenuate beta-adrenoceptor-mediated responses. 3. In both normotensive and hypertensive subjects, the index alpha was reduced by active standing and increased by chronic beta-adrenoceptor blockade. Furthermore, at rest, the index alpha was correlated with R-R variance and appeared significantly reduced with age. The age-related negative correlation of the index alpha was no longer evident during the standing-induced increase in sympathetic drive, in both normotensive and hypertensive subjects. 4. The index alpha, a non-invasive frequency domain estimate of the overall gain of baroreflex control of the sino-atrial node, which appears to be reduced in essential hypertension, is negatively modulated by physiological increases in sympathetic drive, and augmented by pharmacological blockade of beta-adrenoceptors. 5. In essential hypertension the enhanced sympathetic drive present already at rest, and the simultaneous reduction of the gain of baroreflex mechanisms, are the expression of a complex alteration in neural cardiovascular control.

Adult↗

Sympathetic overactivity in subjects complaining of unexplained fatigue.

1. Theoretical and practical considerations suggest that in subjects complaining of fatigue, in the absence of evident organ dysfunction, an alteration in the autonomic nervous system might be present as a functional correlate. 2. Autoregressive spectral analysis of R-R interval variability from a surface ECG, was used in healthy control subjects (n = 24, age 45 +/- 4 years) and in subjects complaining of unexplained fatigue (n = 53, age 46 +/- 9 years) to obtain quantitative indices of the state of the sympathovagal balance, both at rest and during a mental stimulus (mental arithmetic), capable of enhancing sympathetic drive. Sympathetic and vagal modulations were inferred from the normalized powers of the low frequency and high frequency spectral components respectively. 3. We observed in patients, at rest, a prevailing low frequency component of R-R variability (patients low frequency = 73 +/- 11, control subjects 51 +/- 10 normalized units, P < 0.05). The responsiveness to mental arithmetic was reduced in patients as compared with controls. Systolic blood pressure variability did not differ. This suggested a selective imbalance in autonomic control of the sinoatrial node, characterized by sympathetic predominance as well as by vagal withdrawal, at rest. 4. The possibility of discriminating patients from control subjects on the basis of simple non-invasive functional markers might provide a better understanding of the mechanisms, clinical evolution and outcome of conditions such as the chronic fatigue syndrome, which lack ordinary evidence of disease, but comprise, as physiopathological correlate, a quantitative alteration of autonomic control.

Autonomic Nervous System↗

[The effects of chronic cilazapril treatment on sympathetic vasomotor tonus: a spectral analysis study of pressure variability].

Animal experiments suggest that an important component of the antihypertensive effects of ACE inhibitors might derive from an inhibition of the sympathetic vasomotor tone. We addressed this problem on 22 mildly hypertensive subjects (48 +/- 2 years; arterial pressure 151 +/- 3/95 +/- 1 mmHg), in whom sympathetic vasomotor tone was non invasively inferred by the power of the low frequency component (0.1 Hz) of the spontaneous oscillations of systolic arterial pressure (LFSAP), during placebo and after 4 weeks of treatment with a new ACE inhibitor, cilazapril, 5 mg per os oid. LFSAP was computed at rest and during physical (active orthostatism) and mental (computerized attentional test and mental arithmetic) stimuli capable of enhancing sympathetic drive. Cilazapril treatment reduced resting arterial pressure to 128 +/- 3/80 +/- 2 mmHg, without affecting heart rate (78 +/- 2 and 74 +/- 2 b/min, respectively). The increases in LFSAP produced by standing were significantly greater during placebo than during active treatment (delta LFSAP = 10 +/- 3 and 5 +/- 2 mmHg2, respectively). These data suggest that an important reduction of sympathetic vasomotor tone accompanies the antihypertensive effects of chronic ACE-inhibitor treatment.

Blood Pressure↗

Effects of chronic cilazapril treatment on cardiovascular control: a spectral analytical approach.

In 11 subjects with mild hypertension (sitting arterial pressure of 146 +/- 5/97 +/- 2 mm Hg), the effects of chronic angiotensin-converting enzyme (ACE) inhibition (cilazapril, 5 mg p.o. once daily for 4 weeks) were studied at rest and during active standing by means of spectral analysis. Sympathetic vascular control was inferred from the power of the low-frequency (LF) component of the systolic arterial pressure (SAP) variability, assessed noninvasively with a plethysmographic technique. Simultaneously, quantitative indices of neural control of the sinoatrial (SA) node were obtained with the power of the LF and of the high-frequency (respiration linked) component of R-R variability. Before treatment, active standing produced a clear increase in the LF components of R-R and SAP variabilities. At the end of the 4 weeks of cilazapril treatment, the LF component of SAP variability during standing was significantly lower than prior to treatment, while the increase in the LF component of R-R variability was left unchanged. These findings suggest an inhibitory effect of chronic ACE inhibition upon vasomotor sympathetic control, as assessed non-invasively by this technique.

Angiotensin-Converting Enzyme Inhibitors↗

[A noninvasive assessment of the gain in baroceptor control of the heart rate in man].

In this study we addressed the problem of the noninvasive evaluation of the overall gain of baroreceptor control of heart period. We studied a population of healthy controls (n = 49, age 30 +/- 2 years, systolic arterial pressure [by Finapres] 114 +/- 1 mmHg) and a group of mild hypertensive subjects (n = 14, age 51 +/- 2 years, systolic arterial pressure 151 +/- 5 mmHg). Subjects were studied at rest both in absence and in presence of chronic beta-adrenergic receptor blockade (atenolol: controls 50 mg po oid x 4 days; hypertensives 100 mg po oid x 2 weeks). Spectral analysis of RR interval and of systolic arterial pressure variabilities provided noninvasive markers of autonomic control of the SA node and of the vasculature. The index alpha, obtained from bivariate cross spectral and spectral analysis provided a quantitative assessment of the closed loop gain of baroreceptor control of the heart period. The index alpha resulted more elevated in the normotensive than in the hypertensive group. Additionally it appeared significantly increased at the end of the treatment with the beta-adrenergic blocking drug atenolol. Furthermore, alpha appeared significantly and negatively correlated with age, systolic arterial pressure and, although weakly, with low frequency; it was positively correlated with the average RR interval. In conclusion, this study suggested an important link between the average level of sympathetic activity and baroreceptor control of heart rate in normotensive and mild hypertensive subjects. The clinical importance of this sympathetic modulation of the gain of the heart period/arterial pressure relationship can now be assessed with this noninvasive approach.

Adult↗

Adaptational changes in the neural control of cardiorespiratory function in a confined environment: the CNEC#3 experiment.

The goal of the study was to characterize the changes in neurovegetative control of the circulation, attending the presumed physiological and psychological stress originated by the isolation and confinement typical of the living condition of space stations, as simulated in a ground based unit, using time and frequency domain analysis. As a secondary goal we sought to verify the implementation of real time data acquisition, for off line spectral analysis of R-R interval, systolic arterial pressure (by Finapres) and respiration (by PVF2 piezoelectric sensors). We addressed the cardiorespiratory and neurovegetative responses to standardized, simple stressors (active standing, dynamic and static handgrip) on the EXEMSI 92 crew, before, during and after the isolation period. On average the appropriate excitatory responses (to stand, dynamic and static handgrip) were elicited also in isolation and confinement. Active standing and small masses muscular exercises are easy to be performed in a confined and isolated environment and provide a valuable tool for investigating the adaptational changes in neural control mechanisms. The possibility there exists of using this time and frequency domain approach to monitor the level of performance and well being of the space crew in (quasi) real time.

Adaptation, Physiological↗

A controlled study of the effects of mental relaxation on autonomic excitatory responses in healthy subjects.

OBJECTIVE: Circumstantial evidence indicates that, in the presence of a suitable substratum, sudden, behaviorally induced increases in sympathetic drive to the cardiovascular system might play an important physiopathological role in various conditions, ranging from arterial hypertension to sudden coronary death. Accordingly, it might be useful to study the effects of behavioral interventions, such as mental relaxation, that might be capable of blunting excitatory autonomic responses. It would also be preferable to study healthy subjects in whom autonomic control is not modified by the presence of disease, and to use noninvasive approaches to minimize the possible emotional impact produced by invasive recordings. METHODS: We examined healthy subjects who were either subjected to relaxation training (N = 13) or sham relaxation (N = 12). An additional group, treated with beta-adrenergic blockade (N = 12), was also examined. Spectral and cross-spectral analysis of RR interval and systolic arterial pressure (SAP) variabilities provided quantitative markers of sympathovagal balance modulating the sinoatrial (SA) node, of sympathetic vasomotor modulation, and of the gain of the arterial pressure/heart period baroreflex (index alpha). Subjects were studied at rest, during standing, and during mental arithmetic. RESULTS: Data indicate that both beta-adrenergic blockade and relaxation training significantly blunted the excitatory autonomic responses to standing and to mental arithmetic. Indices of sympathetic modulation also seemed reduced by beta blockade at rest. No changes were observed with sham training. CONCLUSIONS: Frequency domain analysis of cardiovascular variabilities, using a totally noninvasive approach, indicates that relaxation training significantly blunts the excitatory autonomic changes produced by standardized behavioral laboratory stimuli.

Adrenergic beta-Antagonists↗