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Biomedical subjects

M Pagani

Publications and source records attributed to M Pagani.

At least 55 records · Page 3Linked to original sources

Assessment of arterial and cardiopulmonary baroreflex gains from simultaneous recordings of spontaneous cardiovascular and respiratory variability.

OBJECTIVES: In usual models of cardiovascular regulation, arterial pressure drives RR interval through a simple baroreflex, and the influence of respiration is dismissed. We examined the applicability of a trivariate autoregressive model to obtain separate values of the gain of the arterial and non-arterial, i.e. cardiopulmonary, components of the lumped baroreflex, employing spontaneous RR interval, systolic arterial pressure and respiration variability. DESIGN: We studied 30 normal subjects (age 37 +/- 1 years), both at rest and during standing, a condition known to enhance sympathetic activity while reducing venous return. Electrocardiogram was obtained by telemetry, arterial pressure by Finapres and respiration with a piezoelectric respiratory belt Data were acquired with a PC and processed with an ad hoc Windows program. METHODS: We employed an additive and a linear multivariate approach to approximate overall gain of the arterial pressure-heart beat period baroreflex (alphalumped) and of its arterial (alphaart) and non-arterial, i.e. cardiopulmonary (alphacp), components, from continuous beat-by-beat series of RR interval, systolic arterial pressure variability and respiration, without using any non-physiological intervention. RESULTS: The overall baroreflex gain at rest (alphalumped = 23.7 +/- 3.4 ms/mmHg) was subdivided into arterial (alphaart = 5.2 +/- 1.0 ms/mmHg) and cardiopulmonary (alphacp = 18.5 +/- 3.2ms/mmHg) components. During active orthostatism, alphaluumped was diminished to 10.0 +/- 2.2 ms/ mmHg. In addition, standing selectively reduced alphacp to 4.8 +/- 1.3 ms/mmHg, while alphaart was not significantly changed. CONCLUSIONS: A trivariate autoregressive model, that considers explicitly the influence of respiration, can subdivide overall, lumped, arterial pressure-heart period baroreflex gain, into two separate components, alphaart and alphacp. Only the latter is reduced by active orthostatism.

Adult↗

Interpreting oscillations of muscle sympathetic nerve activity and heart rate variability.

Computer analysis of spontaneous cardiovascular beat-by-beat variability has gained wide credibility as a means of inferring disturbances of autonomic cardiovascular regulation in a variety of cardiovascular conditions, including hypertension, myocardial infarction and heart failure. Recent applications of spectral analysis to muscle sympathetic nerve activity (MSNA) offer a new approach to a better understanding of the relationship between cardiovascular oscillations and autonomic regulation. However, areas of uncertainty and unresolved debates remain, mostly concerning different methodologies and interpretative models that we will consider in this article. Perusal of all available literature suggests that average sympathetic nerve activity and its oscillatory components, although correlated to some extent, are likely to provide different types of information. In addition, the specific experimental context is of paramount importance, as the rules that seem to govern the relationship between average and oscillatory properties of MSNA appear to be different in usual conditions and in conditions of extremes of activation or disease. In general, dynamic experiments, such as with graded tilt or with vasoactive drugs, are more suited to investigations of the complexity of autonomic regulation than are static comparisons. In addition, because the information is spread across variables and is affected by a potentially large error, it appears that several different techniques should be perceived as complementary rather than as mutually exclusive. Available evidence suggests that low-frequency and high-frequency oscillations in peripheral signals of variability might have a predominantly central, rather than a peripheral, origin and that this applies in particular to low-frequency oscillations. A crucial point in the assessment of the meaning of spectral components relates to consideration of the varying level of very-low-frequency noise, and the mathematical manipulation of derived indices, particularly using a normalization procedure. This appears easier to obtain with auto-regressive than with fast Fourier techniques. With this approach, discrepant interpretations seem to be resolved, provided adequate care is taken in separating direct physiological data from derived meaning, which relates to hidden information and neural codes; in the case of sympathetic discharge, the latter display greater complexity than simple average spike activity per unit time. Accordingly we believe, in conclusion, that the judicious use of spectral methodology, in addition to other techniques, might provide unprecedented, useful insights into autonomic cardiovascular regulation, in both physiopathological and clinical circumstances.

Animals↗

Reproducibility and repeatability of 99Tcm-HMPAO rCBF SPET in normal subjects at rest using brain atlas matching.

The aim of this study was to assess regional cerebral blood flow (rCBF) in normal subjects at rest using 99Tcm-HMPAO single photon emission tomography (SPET). Analysis of reproducibility and repeatability was performed both before and after normalization of flow data. Six healthy volunteers were examined, three times each, according to a routine rCBF protocol. A computerized brain atlas was used to evaluate flow data in eight selected regions. The overall reproducibility of rCBF was evaluated from two scans performed at an average interval of 3 months. Repeatability was evaluated from two scans, 3 h apart and without re-injection of 99Tcm-HMPAO. For the normalized (relative) flow data, the reproducibility was +/- 1.3% and the repeatability +/- 2.2% (i.e. methodological errors dominate). For the non-normalized flow data, the corresponding values were +/- 14.8% and +/- 5.9%. rCBF SPET with 99Tcm-HMPAO is highly reproducible provided that the flow data are normalized. The variation in flow between individuals at one point in time and 3 months later was less than +/- 5% for all brain regions.

Adult↗

Prediction of short cardiovascular variability signals based on conditional distribution.

A new approach measuring the predictability of a process is proposed. The predictor is defined as the median of the distribution conditioned by a sequence of L - 1 previous samples (i.e., a pattern). A function referred to as the corrected mean squared predictor error is defined to prevent the perfect adequacy to the data (i.e., the decrease to zero of the prediction error), thus avoiding to divide the whole set of data in learning and test sets. This function exhibits a minimum and this minimum is taken as a measure of predictability of the series. The use of the minimization procedure avoids to fix a priori the pattern length L. This approach permits one a reliable measure of predictability on short data sequences (around 300 samples). Moreover, this method, in connection with a surrogate data approach, is useful to detect nonlinear dynamics. The analysis indicates that, in simulated and real data, predictability and nonlinearity measures provide different information. The application of this approach to the analysis of cardiovascular variability series of the heart period (RR interval) and systolic arterial pressure (SAP) shows: 1) SAP series is more predictable than RR interval series; 2) predictability of the RR interval series is larger during tilt, during controlled respiration at 10 breaths/min (bpm) and after high-dose administration of atropine; 3) SAP series is dominated by linear correlation; 4) RR interval series exhibits nonlinear dynamics during controlled respiration at 10 bpm and after low-dose administration of atropine, while it is linear during sympathetic activation produced by tilt and after peripheral parasympathetic blockade caused by high-dose administration of atropine.

Adult↗

Registration of neuroimaging data: implementation and clinical applications.

Image registration brings images into a form in which each voxel corresponds to a predetermined anatomic entity and is necessary for comparisons of data across scans. Intrasubject registration is a matter of translating and rotating one image volume into correspondence with another. Intersubject registration is more difficult because it requires the removal of individual anatomy dependence from the data. This article describes, with the help of clinical examples, automated methods for intrasubject registration of scans within and between modalities, and intersubject registration used for registering a three-dimensional brain atlas with a patient's brain scan.

Adult↗

Assessing baroreflex gain from spontaneous variability in conscious dogs: role of causality and respiration.

A double exogenous autoregressive (XXAR) causal parametric model was used to estimate the baroreflex gain (alpha(XXAR)) from spontaneous R-R interval and systolic arterial pressure (SAP) variabilities in conscious dogs. This model takes into account 1) effects of current and past SAP variations on the R-R interval (i.e., baroreflex-mediated influences), 2) specific perturbations affecting R-R interval independently of baroreflex circuit (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at frequencies slower than respiration), and 3) influences of respiration-related sources acting independently of baroreflex pathway (e.g., rhythmic neural inputs modulating R-R interval independently of SAP at respiratory rate, including the effect of stimulation of low-pressure receptors). Under control conditions, alpha(XXAR) = 14.7 +/- 7.2 ms/mmHg. It decreases after nitroglycerine infusion and coronary artery occlusion, even though the decrease is significant only after nitroglycerine, and it is completely abolished by total arterial baroreceptor denervation. Moreover, alpha(XXAR) is comparable to or significantly smaller than (depending on the experimental condition) the baroreflex gains derived from sequence, power spectrum [at low frequency (LF) and high frequency (HF)], and cross-spectrum (at LF and HF) analyses and from less complex causal parametric models, thus demonstrating that simpler estimates may be biased by the contemporaneous presence of regulatory mechanisms other than baroreflex mechanisms.

Animals↗

Study of arterial and autonomic effects of cyclosporine in humans.

Altered sympathetic activity and peripheral vascular function are suspected as a mechanism of the development of arterial hypertension in organ transplantation recipients treated with cyclosporine. We assessed whether cyclosporine might alter peripheral vascular properties or autonomic modulation of the sinus node and the vasculature during rest and standing. We examined 17 orthotopic heart transplantation recipients, 8 solid organ transplantation recipients, 17 patients with essential hypertension, and 42 normotensive control subjects. All except the normotensive control subjects were treated with a long-acting dihydropyridine calcium entry blocker; transplantation recipients also received cyclosporine-based immunosuppression. Radial artery compliance was reduced in patients with essential hypertension and in patients with heart and solid organ transplantation as compared with normotensive control subjects, with this reduction being more marked in heart transplantation recipients. At rest, R-R variance was lowest in heart transplantation recipients, denoting denervation. The spectral profile of both R-R and systolic blood pressure variability as well as the index of baroreflex gain was normal at rest in patients with solid organ transplantation. On standing, both transplantation groups demonstrated reduced responsiveness in markers of autonomic modulation. The decrease in arterial compliance in cyclosporine-induced hypertension seems to imply a degree of ventricular vascular uncoupling more apparent in heart transplantation recipients. These changes are associated with alterations in autonomic modulation that are evidenced by an orthostatic stimulus.

Adult↗

Production of endogenous nitric oxide in chronic obstructive pulmonary disease and patients with cor pulmonale. Correlates with echo-Doppler assessment.

Exhaled nitric oxide (NO) production in stable chronic obstructive pulmonary disease (COPD) has been loosely related to the severity of illness, being significantly reduced in the most severe cases. Pulmonary hypertension is associated with lower NO output from the lung. In this study expired NO was measured in patients with severe stable COPD with or without cor pulmonale (CP). Echocardiographic estimates of right heart function, lung function, diffusion capacity, respiratory muscle strength, and arterial blood gases were obtained in 34 consecutive patients with stable COPD (mean age, 68 +/- 7 yr). Expired NO was measured by chemiluminiscence to obtain fractional exhaled concentrations at peak (FENOp) and at plateau (FENOpl) points of the single-breath curve and resting NO output (V NO). All measurements of expired NO output, FENOp, FENOpl and V NO showed a negative correlation with both systolic pulmonary artery pressure (Pspa) (r = -0.51, -0.63, and -0.63, respectively, p < 0.01 for all) and right ventricle wall dimension (r = -0.41, -0.59, and -0.43, respectively, p < 0.05 for all), but not with any measurement of lung function. When the patients were divided according to the Pspa using a cutoff limit of 35 mm Hg, those subjects with CP showed lower FENOp (13.2 +/- 4.0 versus 36.7 +/- 30.8 ppb, p < 0.05), FENOpl (5.7 +/- 1.9 versus 8.9 +/- 4.7 ppb, p < 0.05), and V NO (69. 2 +/- 5.6 versus 107.6 +/- 14.6 nl/ min, p = 0.02) than did those with a normal resting Pspa. NO production from the airways was significantly lower and inversely related to development of CP in patients with severe COPD. Impaired endothelial release may account for the reduced levels of expired NO.

Aged↗

Hypertension, stress and erectile dysfunction: potential insights from the analysis of heart rate variability.

Increased sympathetic activity and mental stress may affect erectile function. These effects may be acute and/or chronic. Cardiovascular regulation can be assessed non-invasively using a computer-based analysis of suitable haemodynamic signals. This research may provide new insights into the complex pathogenesis of erectile dysfunction (ED). In particular, there is still a largely unexplored area of research that covers the effect of drugs on these regulatory mechanisms. Such research may provide new therapeutic options.

Autonomic Nervous System↗

Heart rate variability and autonomic diabetic neuropathy.

Aim of this paper is to briefly summarize available evidence about potential usefulness of heart rate variability (HRV) analysis for the clinical evaluation of autonomic diabetic neuropathy. HRV contains hidden information that can be extracted from tachogram sections of several hundred beats with spectral analysis. Subsequent normalization and the use of a paradigm including standardized stimuli (such as tilt) are commonly employed to assess autonomic cardiac regulation. In the resulting spectra, two major components of similar amplitude are usually observed (at low--LF--and high frequency--HF), their relative power is best appreciated using normalized units that provide an estimate of the balance between sympathetic and vagal modulatory activity. In states of sympathetic predominance, such as during orthostatic positions, LF increases and HF decreases. In diabetics, consistent alterations in spectral properties are a frequent early finding: initially a reduction of HRV (ie spectral power) is followed by progressive functional denervation, which is associated to severe autonomic dysfunction. The spectral methodology provides some useful potential advantages in respect to the more traditional approach employing several simple bedside tests. In conclusion, spectral analysis of HRV appears a convenient method to assess various degrees of diabetic autonomic dysfunction: it appears easy to perform, while giving results similar to traditional methods, with greater sensibility.

Autonomic Nervous System Diseases↗

Late miocene atmospheric CO(2) concentrations and the expansion of C(4) grasses

The global expansion of C(4) grasslands in the late Miocene has been attributed to a large-scale decrease in atmospheric carbon dioxide (CO(2)) concentrations. This triggering mechanism is controversial, in part because of a lack of direct evidence for change in the partial pressure of CO(2) (pCO(2)) and because other factors are also important determinants in controlling plant-type distributions. Alkenone-based pCO(2) estimates for the late Miocene indicate that pCO(2) increased from 14 to 9 million years ago and stabilized at preindustrial values by 9 million years ago. The estimates presented here provide no evidence for major changes in pCO(2) during the late Miocene. Thus, C(4) plant expansion was likely driven by additional factors, possibly a tectonically related episode of enhanced low-latitude aridity or changes in seasonal precipitation patterns on a global scale (or both).

Journal Article↗

Sympathetic rhythmicity in cardiac transplant recipients.

BACKGROUND: Variability of R-R interval and muscle sympathetic nerve activity (MSNA) occurs predominantly at a low frequency (LF, +/-0.1 Hz) and a high frequency (HF, +/-0.25 Hz) in normal humans. Increased sympathetic drive in normal humans is associated with an increased LF component of the R-R interval and MSNA. Patients with severe heart failure have high sympathetic activity but decreased or absent LF power of both R-R and MSNA. We tested the hypothesis that this dysfunction in autonomic modulation in heart failure can be reversed by heart transplantation. METHODS AND RESULTS: We performed spectral analysis of resting MSNA, R-R interval, and respiration in 9 patients with heart transplants, 9 chronic heart failure patients, and 9 normal control subjects, all closely matched for age, sex, and body mass index. MSNA (bursts per minute) was higher in patients with heart transplants (74+/-3) than either patients with heart failure (56+/-6) or normal subjects (40+/-4) (P<0.001). LF variability in the R-R interval was reduced in both heart transplant recipients and heart failure patients compared with the control subjects (P<0.01). The LF variability in MSNA was also nearly absent in the heart failure patients (P<0.01). However, the LF and HF oscillations in MSNA in patients with heart transplants were comparable to those evident in the control subjects. CONCLUSIONS: Cardiac transplantation does not reduce MSNA. However, LF oscillations in sympathetic activity are restored after transplantation such that the MSNA oscillatory profile is similar to that observed in normal subjects.

Female↗

Dual chamber pacing with optimal AV delay in congestive heart failure: a randomized study.

AIM: A prospective randomized trial was set up to evaluate contractile parameters and quality of life in patients with congestive heart failure. METHODS AND RESULTS: We describe the results from 38 patients in sinus rhythm and with chronic heart failure due to congestive cardiomyopathy, prospectively randomized to optimal medical therapy (Group 1, 19 patients) or optimal medical therapy plus dual chamber pacemaker programmed to optimal AV delay (Group 2, 19 patients). At a 6 month follow-up, 7/19 patients in Group 1 had died compared with 5/19 patients in Group 2. During follow-up, there were few significant changes in evaluated parameters except for mitral regurgitation time, which was prolonged in Group 1 and shortened in Group 2. The systolic left ventricular diameter shortened significantly only in Group 2. An energy and activity questionnaire showed that the effect of DDD pacing in the latter patient population was beneficial. CONCLUSIONS: From these results we may conclude that at the 6 month follow-up DDD pacing with echo-optimized AV interval programming can improve quality of life without affecting survival.

Aged↗

Cardiac autonomic adjustments to normal human pregnancy: insight from spectral analysis of R-R interval and systolic arterial pressure variability.

OBJECTIVE: To assess the adaptation in autonomic control mechanisms that accompanies the marked haemodynamic changes, such as increases in cardiac size and output, that occur in the course of normal human pregnancy. DESIGN: We studied 14 healthy pregnant women (aged 30+/-1 years) before the 6th week (early stage) and within weeks 32-34 (late stage) of pregnancy, while they were at rest or in a state of active orthostatism (standing), which enhances sympathetic activity. METHODS: We used echocardiography to assess cardiac volumes and mass, and spectral analysis of the R-R interval and systolic arterial pressure variability to obtain indices of autonomic regulation of the circulation. This non-invasive methodology, recently validated with direct recordings of muscle sympathetic nerve activity, furnishes quantitative markers of sympathetic modulation of the sino-atrial node (low frequency component, LF in normalized units, nu), vagal modulation (high frequency component, HF in normalized units, nu) and the overall arterial pressure-heart rate baroreflex gain (alpha index). RESULTS: Late pregnancy was characterized by an increase in cardiac size and volumes and by a reduction of R-R interval, R-R interval variance and the alpha index, together with an increase in the LF/HF ratio (from 1.4+/-0.4 to 5.6+/-1.9). Changes in markers of autonomic modulation of the sino-atrial node normally induced by the standing position were blunted. CONCLUSIONS: The late stage of normal human pregnancy appears to be characterized by alterations in the autonomic control of the circulation and by attenuated responsiveness to active standing, possibly as a consequence of the accompanying increase in cardiac size.

Adult↗

Complications of subcutaneous infusion port in the general oncology population.

Subcutaneous infusion ports (SIPs) represent a valid method for long-term chemotherapy. The SIPs have several advantages over other methods of venous access: they are easy to implant under local anaesthesia, have less discomfort for the patients, allow low costs, can be implanted in day hospital, and can be managed ambulatorily. However, SIPs have delayed complications, frequently related to clinical conditions of the neoplastic patients, and immediate complications, often due to the placement technique. From March 1992 to March 1997 we placed, under local anaesthesia and under fluoroscopic control, 102 SIPs in 99 general oncology patients for long-term chemotherapy (88% solid, 12% haematological tumours). The percutaneous venous access devices were in the subclavian vein in 96% of the cases and in the internal jugular vein in 4% of them. Immediate complications were: 1 haemopneumothorax, which required thoracic aspirations and two blood transfusions, 1 loop of the tunneled part of the catheter without alterations in SIP function, and 1 left jugular thrombosis in a patient with subclavian veins already thrombosed. The venous access was in the subclavian vein in the first 2 cases, and it was not necessary to suspend the therapeutic program. In the third instance, implanted in jugular vein, it was necessary to remove the SIP. Delayed complications were: 1 necrosis of the skin over the port, 1 infection of subcutaneous pocket, 2 infections of the system, 1 catheter deconnection, and 3 catheter ruptures with embolization of the catheter tip. The SIPs were removed in all cases but 1 in whom infection was successfully treated by appropriate antibiotic therapy. Embolization of the catheter required removal from the pulmonary artery under fluoroscopic guidance in the cardiac catheterization laboratory. In conclusion, infection and thrombosis are the two major complications of SIP in general oncology patients. In these cases it is not necessary to remove systematically the system, but a correct therapy (antibiotic, fibrinolytic agents) can be utilized with good results. The catheter rupture is often due to the wear over the costoclavicular angle. The interventional radiology is the method of choice in the treatment of the catheter embolization by rupture or dislocation. The experience of the surgical and nursing staff is probably the most important factor in decreasing the total rate of complications.

Antineoplastic Agents↗

Effects of oxygen on autonomic nervous system dysfunction in patients with chronic obstructive pulmonary disease.

Chronic hypoxaemia can play a pathological role in abnormalities of the autonomic nervous system (ANS). In patients with chronic obstructive pulmonary disease (COPD), chronic hypoxaemia is associated with increased mortality and only long-term oxygen therapy is able to improve their survival. Normoxaemic COPD patients have been shown to suffer from abnormalities in ANS function. The aims of this study were to evaluate ANS function in COPD patients with chronic hypercapnic respiratory insufficiency and to test whether oxygen supplementation could reverse any ANS dysfunction. Eleven stable COPD patients with chronic hypercapnic respiratory insufficiency underwent evaluation of ANS by analysis of variability in cardiac frequency at rest and during both vagal (controlled breathing) and sympathetic (tilting) stimuli breathing with and without oxygen supplementation. Thirteen male, healthy, nonsmoking volunteers served as controls. Evaluation of ANS in COPD patients during hypoxic conditions showed alterations both at rest and in response to vagal and sympathetic stimuli. Oxygen supply reversed hypoxaemia without significant changes in arterial carbon dioxide tension and, therefore, ANS alterations were corrected during sympathetic stimulus only. Breathing room air and oxygen, the resting low-frequency (LF) powers were 45+/-15 and 148+/-55 ms2 x Hz(-1), respectively, and controlled breathing LF were 107+/-41 and 141+/-113 ms2 x Hz(-1), respectively. In stable patients with chronic obstructive pulmonary disease with chronic respiratory insufficiency, hypoxaemia is associated with derangements in the autonomic nervous system which may be partially reversed by oxygen administration.

Aged↗