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Biomedical subjects

M Pagani

Publications and source records attributed to M Pagani.

At least 109 records · Page 6Linked to original sources
PubMed1995

Immunological reactivity in ranitidine factory workers.

The involvement of immunological reactivity to ranitidine base (R-b) and ranitidine hydrochloride (R-HCl) in the development of occupationally related symptomatology was analyzed in 40 subjects employed in a pharmaceutical plant producing ranitidine and in 33 nonexposed controls, using a specific dose-response lymphocyte proliferative test (lymphocyte transformation test: LTT). Of the 40 workers, 11 (28%) gave positive reactions to LTT: 3/11 to R-b, 4/11 to R-HCl, and 4/11 to both compounds. None of the controls gave positive reactions. Cutaneous, oculonasal, or respiratory work-related symptoms were cited by 23 of the 40 (58%) subjects; ten of these 23 subjects (43%) were LTT positive. One asymptomatic case was LTT positive. The present results indicate that specific immune reactivity to ranitidine, analyzed by LTT, is associated with the presence of occupational symptomatology; R-HCl and R-b seem to share some antigenic determinants, because of the partial cross-reactivity shown by the examined compounds. Nonimmunological, probably irritative, mechanisms are also present in some of the symptomatic subjects.

Eye Diseases↗
PubMed1995

Progression of atrophy of the corpus callosum with deterioration of cerebral cortical oxygen metabolism after carotid artery occlusion: a follow up study with MRI and PET.

In cerebrovascular disease, progression of brain atrophy may reflect an increase in ischaemic changes. The purpose of this study was to determine whether atrophy of the corpus callosum progresses in association with a deterioration in cerebral cortical oxygen metabolism after occlusion of the carotid artery. Magnetic resonance imaging and PET were used to serially evaluate six patients with occlusion of the unilateral internal carotid artery at intervals ranging from 12 to 50 months. One patient had no symptoms, one had a transient ischaemic attack, and four had a minor stroke. All patients had presented at most only subcortical lesions at the first evaluation. During follow up, no patient showed extension of subcortical lesions or recurrent stroke. The initial total callosal area:skull area ratio for the patients was significantly less than that for 14 age matched normal control subjects. The yearly decrease of callosal size in the patients, which differed significantly from zero and exceeded that in the controls, was significantly correlated with the deterioration in mean cerebral cortical oxygen metabolism. Three of the four patients who showed significant progression of callosal atrophy presented deterioration in haemodynamic states as well. It is concluded that in some patients atrophy of the corpus callosum progresses after occlusion of the carotid artery even in the absence of any overt episode of stroke, and that this atrophy is associated with deterioration in cerebral cortical oxygen metabolism. An increase in cerebral morphological changes with deterioration in cerebral metabolism related to ischaemia may occur after occlusion of the carotid artery, even in the absence of symptoms.

Aged↗
PubMed1995

Ultra-high resolution SPECT system using four pinhole collimators for small animal studies.

UNLABELLED: We describe a newly developed ultra-high resolution SPECT system using four pinhole collimators for small animal studies. METHODS: The system utilizes a clinical four-head SPECT scanner with specially designed pinhole collimators. Four types of pinholes with different configurations were designed with different effective aperture sizes (1.0, 2.0 and 4.0 mm) and rotating radii (40 mm and 50 mm). The distance from the axis of rotation to the scintillator was fixed to 180 mm. A filtered backprojection algorithm was used to reconstruct SPECT images after fanbeam-to-parallel-beam data conversion. RESULTS: The system provided a reconstructed spatial resolution of 1.65 mm (FWHM) and sensitivity of 4.3 kcps/microCi/ml with the best type of pinholes, respectively. The 99mTc-HMPAO SPECT image in rat studies clearly visualized small brain structures, and the left ventricular myocardium and cardiac cavity were clearly separated with 99mTc-MIBI. Dynamic SPECT imaging of rat brain with [123I]iomazenil was also feasible. CONCLUSION: This ultra-high resolution SPECT system can be used to measure the regional distribution of radiolabeled tracers in small animals in vivo and may play a significant role in the development of new radiopharmaceuticals and in studies of various disease models using living animals.

Animals↗
PubMed1995

A circadian perspective on myocardial ischaemia.

The non-uniform occurrence of myocardial ischaemia, with a trough at night and a peak in the morning, is at the base of the concept of a circadian distribution of coronary events. Cardiovascular variables known to influence the occurrence of ischaemia have similar rhythms, and a likely culprit could be hidden among them. Nevertheless, in many cases an identifiable trigger is lacking and the prediction of ischaemia is still elusive.

Autonomic Nervous System↗
PubMed1995

Mechanical effects of respiration and stepping on systolic arterial pressure variability during treadmill exercise.

AIM: To evaluate the changes produced by maximal dynamic exercise in the rhythmic components of systolic arterial pressure variability. PATIENTS AND METHODS: We studied seven normotensive subjects during different levels of a modified treadmill test (Bruce protocol, up to stage 4). Arterial pressure was measured directly by a high-fidelity microtip pressure transducer. Spectral analysis provided two main oscillatory components of systolic arterial pressure variability, a low-frequency component related to the sympathetic-mediated neural control of vasomotion and a high-frequency component reflecting the mechanical effects of respiration on blood pressure. RESULTS: The low-frequency component increased at the beginning of exercise and remained stable thereafter, while the high-frequency component increased progressively. A third rhythmic component (very high frequency) with a frequency higher than respiration and synchronous with the rate of the subjects' footsteps, which was undetectable on a visual inspection of analog tracings, became progressively more apparent, reaching its maximum at exercise stage 4. CONCLUSIONS: These findings emphasize the importance of high-fidelity techniques and computer analysis for the evaluation of arterial pressure variability in dynamic conditions.

Adult↗
PubMed1995

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↗
PubMed1994

Physiology and clinical implications of variability of cardiovascular parameters with focus on heart rate and blood pressure.

Power spectral analysis of heart period (R-R) and arterial pressure short-term variability reveals the existence of two rhythmic oscillations: a high frequency (HF) component corresponding to respiratory activity (around 0.25 Hz) and a low frequency (LF) component corresponding to vasomotor waves (around 0.10 Hz). Further, a very low frequency (VLF) component, with a center frequency around 0 Hz, can be identified. It is generally accepted that the power of the HF component of R-R variability is a marker of vagal activity to the sinoatrial node. We have introduced the hypothesis, which is becoming progressively accepted, that the LF component of R-R variability is a marker of sympathetic modulation of the sinoatrial node, whereas the LF component of arterial pressure variability is a marker of sympathetic modulation of vasomotor tone. Moreover, we have suggested that the evaluation (in normalized units) of the LF and HF components of R-R variability (or the LF/HF ratio) can assess the state of the sympatho-vagal balance modulating the sino-atrial node in numerous physiologic and physiopathologic conditions. A large body of evidence has been gathered on the basis of multiple recordings of cardiovascular signals obtained in humans and in acute and chronic animal experiments in favor of this hypothesis.

Blood Pressure↗
PubMed1994

Model for the assessment of heart period and arterial pressure variability interactions and of respiration influences.

A model which assesses the closed-loop interaction between heart period (HP) and arterial pressure (AP) variabilities and the influence of respiration on both is applied to evaluate the sources of low frequency (LF approximately 0.1 Hz) and high frequency (HF, respiratory rate approximately 0.25 Hz) in conscious dogs (n = 18) and humans (n = 5). A resonance of AP closed-loop regulation is found to amplify LF oscillations. In dogs, the resonance gain increases slightly during baroreceptor unloading (mild hypotension obtained with nitroglycerine (NTG) i.v. infusion, n = 8) and coronary artery occlusion ((CAO), n = 6), and it is abolished by ganglionic transmission blockade ((ARF), Arfonad i.v. infusion, n = 3). In humans, this gain is considerably increased by passive tilt. Different, possibly central, sources of LF oscillations are also evaluated, finding a strong rhythmic modulation of HP during CAO. At HF, a direct respiratory arrhythmia is dominant in dogs at control, while it is considerably reduced during CAO. On the contrary, in humans, a strong influence of respiration on AP is shown which induces a reflex respiratory arrhythmia. An index of the gain of baroreceptive response, alpha cl, was decreased by NTG and CAO, and virtually abolished by chronic arterial baroreceptive denervation (TABD, n = 4) and ARF.

Animals↗
PubMed1994

Altered dynamics of the circadian relationship between systemic arterial pressure and cardiac sympathetic drive early on in mild hypertension.

1. This study was designed to test the hypothesis that simultaneous non-invasive assessment of the circadian variations in both intermittent arterial pressure and the continuous 24 h changes of spectral markers of cardiac neural control could provide new information on cardiovascular regulatory mechanisms, in hypertensive patients and normotensive subjects. To test this hypothesis we studied 18 subjects with mild hypertension and 11 normotensive subjects in whom we recorded simultaneously non-invasive intermittent arterial pressure and Holter electrocardiogram for 24 h. We also studied the same subjects during resting and standing conditions in the clinical laboratory. 2. The normalized power of the low-frequency (approximately 0.1 Hz) spectral component of R-R interval variability, considered mainly a marker of sympathetic drive to the sino-atrial node, was, at rest, significantly higher in the hypertensive than in the normotensive subjects, as already reported. Moreover, the values of the low-frequency component at rest recorded in the clinical laboratory were significantly correlated with those obtained from ambulatory recording during night rest. The decrease in the values of arterial pressure during the night-time was accompanied by a reduction in the power of the low-frequency component only in the case of normotensive subjects. Accordingly, the slope of the regression of the low-frequency component as a function of systolic arterial pressure during ambulatory recordings was steep in normotensive subjects and flat in hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Power spectral analysis of cardiovascular variability in patients at risk for sudden cardiac death.

The time series of successive heart periods present important variations around its mean value, determining the phenomenon of heart rate variability (HRV), assessed with both time and frequency domain approaches. A low standard deviation of the heart period (a time domain index of HRV) is a powerful prognostic indicator of sudden coronary death in patients recovering from acute myocardial infarction. Spectral analysis of HRV usually demonstrates two major components: indicated as LF (low frequency, approximately 0.1 Hz) and HF (high frequency, approximately 0.25 Hz). They are defined by center frequency and associated power, which is expressed in msec2 or normalized units. When assessed in normalized units, LF and HF provide quantitative indicators of neural control of the sinoatrial node. Numerous experimental and clinical studies have consistently indicated that the LF component is a marker of sympathetic modulation and HF a marker of vagal modulation; the LF/HF ratio is a synthetic index of sympathovagal balance. In the analysis of 24-hour Holter recordings of normal subjects, a circadian rhythmicity of spectral markers of sympathetic and vagal modulation is clearly present, with a sympathetic predominance during the day and a vagal predominance during the night. In patients recovering from an acute myocardial infarction, spectral analysis of HRV revealed an increased sympathetic and decreased vagal activity during early convalescence, and a return to their normal balance by 6 to 12 months. A clear increase of LF was also evident in patients studied within a few hours of the onset of symptoms related to an acute myocardial infarction, independent of its location. Similarly, LF increased during transient myocardial ischemia. An increase in markers of sympathetic activity has also been observed prior to episodes of malignant arrhythmias. Spectral analysis of HRV could help in the understanding of the role of abnormal neural mechanisms in sudden coronary death, thus contributing to its prevention.

Death, Sudden, Cardiac↗
PubMed1994

Restraining effects of captopril on sympathetic excitatory responses in dogs: a spectral analysis approach.

This study was planned to clarify the effects of captopril administration on the autonomic control of the circulation in conscious dogs and in dynamic conditions using spectral analysis of R-R interval and systolic arterial pressure (SAP) variabilities. Changes in sympathovagal balance modulating the sinoatrial (SA) node were inferred, respectively, from the low (LFR-R)- and high-frequency (HFR-R) components of R-R variability; LFSAP furnished a marker of sympathetic vasomotor control. Increases in sympathetic activity were induced by three different experimental maneuvers [bilateral carotid occlusion (BCO), coronary artery occlusion (CAO), and dynamic exercise] capable of increasing sympathetic outflow to the SA node and to the vessels. Studies were performed both before and after intravenous captopril administration. During BCO, only LFSAP increased from 4.3 +/- 1.5 to 19.7 +/- 4.1 mmHg2; during CAO, both LFR-R and LFSAP increased, respectively, from 3 +/- 1 to 21 +/- 2 normalized units (nu) and from 4.1 +/- 1.3 to 7.2 +/- 1.5 mmHg2. Dynamic exercise at 2 and 4 km/h progressively raised LFR-R from 8 +/- 2 to 58 +/- 7 and 75 +/- 5 nu, respectively; LFSAP showed a parallel trend increasing from 2.5 +/- 0.7 to 8.04 +/- 1.9 and 12.7 +/- 2.2 mmHg2. In all experimental conditions, captopril significantly (P < 0.05) blunted the increase of LFSAP. A restraining effect on LFR-R was apparent only with CAO. Spectral analysis of cardiovascular variabilities indicates that, in the conscious dog, acute captopril administration has an important inhibitory effect on cardiac sympathetic excitatory mechanisms as well as on sympathetic vasomotor control.

Animals↗
PubMed1994

Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt.

BACKGROUND: The powers of the low-frequency (LF) and high-frequency (HF) oscillations characterizing heart rate variability (HRV) appear to reflect, in their reciprocal relationship, changes in the state of the sympathovagal balance occurring during numerous physiological and pathophysiological conditions. However, no adequate information is available on the quantitative resolution of this methodology. METHODS AND RESULTS: We studied 22 healthy volunteers (median age, 46.5 years) who were subjected after a rest period to a series of passive head-up tilt steps randomly chosen from the following angles: 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 90 degrees. From the continuous ECG, after appropriate analog-to-digital conversion, a personal computer was used to compute, with an autoregressive methodology, time and frequency domain indexes of RR interval variability. Spectral and cross-spectral analysis with the simultaneously recorded respiratory signal excluded its contribution to LF. Age was significantly correlated to variance and to the absolute values in milliseconds squared of very-low-frequency (VLF), LF, and HF components. The tilt angle was correlated to both LF and HF (expressed in normalized units [nu]) and to the LF-to-HF ratio (r = .78, -.72, and .68; respectively). Lower levels of correlation were found with HF (in ms2) and RR interval. No correlation was present between tilt angle and variance, VLF, or LF (in ms2). Individual analysis confirmed that the use of nu provided the greatest consistency of results. CONCLUSIONS: Spectral analysis of HRV, using nu or LF-to-HF ratio, appears to be capable of providing a noninvasive quantitative evaluation of graded changes in the state of the sympathovagal balance.

Adult↗