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Biomedical subjects

S Cavalcanti

Publications and source records attributed to S Cavalcanti.

At least 19 recordsLinked to original sources

Real-time supervisor system based on trinary logic to control experiments with behaving animals and humans.

A new method is presented based on trinary logic able to check the state of different control variables and synchronously record the physiological and behavioral data of behaving animals and humans. The basic information structure of the method is a time interval of defined maximum duration, called time slice, during which the supervisor system periodically checks the status of a specific subset of input channels. An experimental condition is a sequence of time slices subsequently executed according to the final status of the previous time slice. The proposed method implements in its data structure the possibility to branch like an if-else cascade and the possibility to repeat parts of it recursively like the while-loop. Therefore its data structure contains the most basic control structures of programming languages. The method was implemented using a real-time version of LabVIEW programming environment to program and control our experimental setup. Using this supervision system, we synchronously record four analog data channels at 500 Hz (including eye movements) and the time stamps of up to six neurons at 100 kHz. The system reacts with a resolution within 1 ms to changes of state of digital input channels. The system is set to react to changes in eye position with a resolution within 4 ms. The time slices, experimental conditions, and data are handled by relational databases. This facilitates the construction of new experimental conditions and data analysis. The proposed implementation allows continuous recording without an inter-trial gap for data storage or task management. The implementation can be used to drive electrophysiological experiments of behaving animals and psychophysical studies with human subjects.

Animals↗

Electrophysiological response to dialysis: the role of dialysate potassium content and profiling.

UNLABELLED: The task of dialysis therapy is, amongst other things, to remove excess potassium (K+) from the body. The need to achieve an adequate K+ removal with the risk of cardiac arrhythmias due to sudden intra-extracellular K+ gradient advises the distribution of the removal throughout the dialysis session instead of just in the first half. The aim of the study was to investigate the electrical behavior of two different K+ removal rates on myocardial cells (risk of arrhythmia and ECG alterations). Constant acetate-free biofiltration (AFB) and profiled K+ (decreasing during the treatment) AFB (AFBK) were used in a patient sample to understand, first of all, the effect on premature ventricular contraction (PVC) and on repolarization indices [QT dispersion (QTd) and principal component analysis (PCA)]. The study was divided into two phases: phase 1 was a pilot study to evaluate K+ kinetics and to test the effect on the electrophysiological response of the two procedures. The second phase was set up as an extended cross-over multicenter trial in patient subsets prone to arrhythmias during dialysis. Phase 1: PVC increased during both AFB and AFBK but less in the latter in the middle of dialysis (298 in AFB vs. 200 in AFBK). The PVC/h in a subset of arrhythmic patients was 404 +/- 145 in AFB and 309 +/- 116 in AFBK (p = 0.0028). QT interval (QTc) prolongation was less pronounced in AFBK than in AFB. Phase 2: The PVC again increased in both AFB and AFBK but less in the latter mid-way through dialysis (79 +/- 19 AFB vs. 53 +/- 13 AFBK). Moreover, in the most arrhythmic patients the benefit accruing from the smooth K+ removal rate was more pronounced (103 +/- 19 in AFB vs. 78 +/- 13 in AFBK). CONCLUSION: It is not the K+ dialysis removal alone that can be destabilizing from an electrophysiological standpoint, but rather its removal dynamics. This is all the more evident in patients with arrhythmias who benefit from the K+ profiling during their dialysis treatment.

Adult↗

alpha-Amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors in spinal cord motor neurons are altered in transgenic mice overexpressing human Cu,Zn superoxide dismutase (Gly93-->Ala) mutation.

There are many evidences implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). This neurodegenerative disorder is characterized by the progressive loss of motor neurons, whose pathogenesis is thought to involve Ca(2+) influx mediated by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptors (AMPARs). In the present study we report alterations in the AMPARs function in a transgenic mouse-model of the human SOD1(G93A) familial ALS. Compared with those expressed in motor neurons carrying the human wild type gene, AMPAR-gated channels expressed in motor neurons carrying the human mutant gene exhibited modified permeability, altered agonist cooperativity between the sites involved in the process of channel opening and were responsible for slower spontaneous synaptic events. These observations demonstrate that the SOD1(G93A) mutation induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS.

Alanine↗

Numerical simulation of flow oscillations in stenotic arterial segment.

The hypothesis that stenosis-induced flow disturbances may be the cause of vascular sounds was investigated. The onset of flow oscillations in a vessel with a severe constriction was simulated by a computer model based on the axi-symmetric Navier-Stokes equations. Model includes fluid non-linear inertial forces, viscoelastic wall motion, anatomical taper and proximal and distal circulation. Self-excited flow oscillations with different oscillatory patterns were reproduced. A common characteristic of such flow oscillations was a high-frequency component in the audible band (100-500 Hz). Numerical results support the hypothesis that vascular sounds may be generated by high-frequency flow oscillations.

Animals↗

Analysis by mathematical model of haemodynamic data in the failing Fontan circulation.

Several late complications jeopardize the clinical performance of recipients of the Fontan operation. The underlying causes have been referred to disturbed flow dynamics in the cavopulmonary connections. Presumably, the large pressure drops occurring in the inferior and superior connections play a pivotal role in the pressure level of the entire circulation, especially in the venous. To address this issue, we retrospectively reviewed catheterization data of six patients with failing Fontan circulation and compared them with those of six patients with functioning Fontan circulation. The impact on the systemic and pulmonary pressure of the increase in the cavopulmonary connection resistances was studied through a steady-state mathematical model of the univentricular closed-loop circulation. In the patients with failing Fontan, pressure in the venae cavae was found to be significantly higher, especially at the inferior cava (19.3 +/- 2.2 versus 12.5 +/- 2.3 mmHg) with the pressure drop at the inferior cavopulmonary connection significantly increased (4.7 +/- 3.1 versus 0.33 +/- 0.82 mmHg). The proposed mathematical model permits us to clearly relate the pressure increase in the venae cavae to an increased resistance in the cavopulmonary connections. Therefore, the present analysis confirms that, to avoid possible congestion of venous circulation, the definitive palliation of univentricular heart should not cause pressure drops at the cavopulmonary connections.

Adolescent↗

Validation of automated oscillometric sphygmomanometer (HDBPM) for arterial pressure measurement during haemodialysis.

An HDBPM oscillometric sphygmomanometer used for the automatic measurement of arterial blood pressure is evaluated according to the ANSI/AAMI SP10-1992 standard. The accuracy of the HDBPM is ascertained by comparing it against the standard Riva-Rocci ascultatory method. Following the ascultatory method, two independent observers use the HDBPM devise to simultaneously measure the arterial blood pressure in 92 subjects of varying ages and having different blood pressures and arm sizes. High agreement is found when comparing the observers' pressure determinations (within 10 mmHg for 100% of observations). Correlation between the average of two ascultatory determinations and the HDBPM is high both for the systolic (r = 0.98) and diastolic (r = 0.94) pressures. The mean of the differences between the pressures measured by the observers and the HDBPM device are 0.2 mmHg (systolic) and -0.4 mmHg (diastolic). The percentages of readings within 10 mmHg between those taken by the observers and those taken by the HDBPM are 88% (systolic) and 97% (diastolic). These results largely satisfy current requirements.

Adolescent↗

Arterial baroreflex influence on heart rate variability: a mathematical model-based analysis.

The influence of the arterial baroreflex on the heart rate variability is analysed by using a mathematical model of heart rate baroreceptor control. The basic mechanisms of the model, sufficient to elicit heart rate variability include: systemic circulation, a non-pulsatile cardiac pump and nonlinear negative feedback simulating arterial baroreflex closed-loop control of the heart rate (-3 bpm/mmHg as maximum reflex sensitivity). The latter reproduces, through two distinct delayed branches (0.8 and 2.8 s), the short-term autonomic control effected respectively by sympathetic and parasympathetic divisions on the sinus node. By means of this model, two distinct self-sustained oscillatory components with incommensurate frequencies (0.1 and 0.26 Hz) are reproduced. Frequencies of these two oscillatory components closely agree with the main heart rate rhythms in humans (0.09 +/- 0.01 Hz and 0.26 +/- 0.01 Hz). When sympathetic-mediated regulation prevails over parasympathetic activity, simulated heart rate oscillation is characterised by a low frequency (approximately 0.1 Hz). On the other hand, a high-frequency oscillatory component (approximately 0.26 Hz) appears when enhanced vagal activation or partial inhibition of the sympathetic control is simulated. When both autonomic divisions are operative, both low- and high-frequency components are present and the heart rate oscillates quasi-periodically. This variability in heart rate at different frequencies is reproduced without including outside perturbations and is due to the nonlinear delayed structure of the closed-loop control. Bifurcation theory of nonlinear system is used to explain the high sensitivity of the heart rate oscillatory pattern to model parameter changes.

Baroreflex↗

Electrolyte and pH dependence of heart rate during hemodialysis: a computer model analysis.

The influence of hemodialysis-induced modifications in extracellular fluid characteristics on heart rate was investigated by using a detailed computer model of sinus-node electrical activity. Changes similar to those occurring in the course of hemodialysis in extracellular concentrations of sodium (from 138 to 140 mM), potassium (from 6 to 3.3 mM), and calcium (from 1.2 to 1.5 mM) ions as well as in pH (from 7.31 to 7.4) and intracellular volume were simulated. The model predicted that such changes may largely influence the rhythm of the sinoatrial node pacemaker, causing the heart rate to range from 69 to 86 bpm. Heart rate increases after removing potassium (up to 7 bpm) and also after calcium perfusion (up to 11 bpm) whereas restoring pH slows heart beat (up to 6 bpm). Extracellular sodium has no significant influence, but the heart rate strictly depends on intracellular sodium concentration (5 bpm/mM). A complex dependence of heart rate on electrolytes and pH was also recognized. Providing extracellular potassium concentration is maintained above 5 mM, heart rate exhibits low sensitivity to changes in calcium and potassium. When potassium concentration is reduced below 4.5 mM, heart rate sensitivity to calcium and potassium increases significantly to 10 and 30 bpm/mM, respectively. A sustained increase in heart rate always corresponds to an increase in intracellular sodium concentration.

Acetylcholine↗

Hemodynamic and mechanical performance of arterial grafts assessed by numerical simulation: a design oriented study.

The hemodynamic and mechanical characteristics of an end-to-end implanted prosthesis for a small artery were theoretically investigated. The changes in the main physical and geometrical properties of the prosthesis were simulated by means of a numerical model of arterial hemodynamics. Variation in the pressure-radius curve due to changes in lumen size, wall thickness, elasticity, and tapering were considered. The effects of such changes on pressure, flow, and wall stresses during the cardiac cycle were evaluated. To avoid superimposing the effects, only 1 of the graft properties was varied with respect to a reference condition in each simulation. A prosthesis with a reduced lumen size (20%) was subjected to higher shear stress, which was dangerously doubled. Wall thickening (200%) primarily determined decreased circumferential stress (300%) and increased wall shear stress (48%) because it caused a reduction of the graft lumen size. The time averages of flow and pressure over the cardiac cycle were not significantly influenced by the simulated changes, being imposed primarily by the proximal and distal circulations.

Biomechanical Phenomena↗

Numerical simulation of the hemodynamic response to hemodialysis-induced hypovolemia.

To provide a framework for analyzing cardiovascular response to hemodialysis-induced hypovolemia, we developed a computer model which simulates arterial pressure changes caused by loss of blood volume. The model includes arterial and venous systemic circulation, Starling's law and inotropic regulation of heart, arterial and cardiopulmonary baroreflex control of capacitance, and resistance vessels. The performance of this model was assessed by analyzing the hemodynamic responses recorded in 12 patients undergoing chronic hemodialysis, 6 classified as hypotension resistant (stable group) and 6 as hypotension prone (unstable group). Arterial pressure, heart rate, and blood volume were recorded during regular hemodialysis. Blood volume and heart rate were used as inputs to the simulator whereas the arterial pressure response obtained by simulation was fitted to the measured data by tuning simulator parameters relative to the capacitance and resistance controls. Although analyzed pressure responses exhibited a wide variety of time patterns, for each one it was possible to identify an optimal set of parameters allowing the recorded pressure data to be accurately reproduced by the model. Sensitivity analysis performed with the model indicated that pressure response strongly depends on the parameter Kv accounting for the capability to control vascular capacitance. According to these results, the parameter Kv in the stable group was 9 times that of the unstable group, thereby suggesting a possible cause of their different hemodynamic behavior.

Analysis of Variance↗

Analysis of oscillatory components of short-term heart rate variability in hemodynamically stable and unstable patients during hemodialysis.

Short period oscillatory components embedded in heart rate variability (HRV) were studied during hemodialysis induced hypovolemia in 15 hypotension-resistant (stable) and 15 hypotension-prone (unstable) patients. Hemodialysis was undertaken so that a similar blood volume reduction was induced in all patients (p > 0.05) without causing acute hypotension events. Autoregressive HRV power spectrums were calculated using an eigenanalysis-based approach. The frequencies of the main HRV rhythmic components were estimated through the Pisarenko harmonic decomposition. Percent changes during the hemodialysis in both heart rate and arterial pressure were similar in the stable and unstable groups (p > 0.05). The HRV spectral density showed markedly different power distributions. In the stable patients, power was mainly in the low frequency band (74+/-7 nU in the low frequency [LF] band vs. 21+/-6 nU in the high frequency [HF] band) whereas in stable patients, it was mainly in the high frequency band (39+/-10 nU in the LF band vs. 47+/-7 nU in the HF band). The frequency of the main oscillation was 0.1+/-0.02 Hz in stable patients and 0.18+/-0.04 Hz in unstable ones (p < 0.01). These HRV spectral parameters have a clear diagnostic value in discriminating between stable and unstable patients when their hemodynamic behaviors are similar.

Adult↗

Autonomic nervous function during haemodialysis assessed by spectral analysis of heart-rate variability.

1. Short-term autonomic response to haemodialysis-induced hypovolaemia was studied in 30 patients undergoing chronic haemodialysis by analysing power spectra of heart-period variability. Patients were classified as haemodynamically stable (15 patients) and unstable (15 patients) according to their past history of cardiovascular collapse during the treatment. Blood volume, systolic arterial pressure and heart period were measured during sessions that ended without the occurrence of collapse. 2. No significant differences were observed when comparing blood volume, heart rate and arterial pressure of stable and unstable patients during the dialysis, and the two groups could not be distinguished merely on the basis of these haemodynamic parameters. Conversely, spectral analysis of beat-to-beat heart-period variability showed markedly different power patterns: in stable patients power was mainly in the low-frequency (LF) band (0.06-0.15 Hz), whereas in unstable patients it was mainly in the high-frequency (HF) band (0.15-0.4 Hz). 3. The efficiency of the autonomic response to hypovolaemia was evaluated by the ratio between the powers in the LF and HF bands. Stable patients exhibited an LF/HF power ratio systematically greater than unstable patients during the entire dialysis, and on the basis of this index the two groups were clearly separated. 4. Results obtained with spectral analysis lead us to conclude that reduced efficiency in the autonomic control of cardiovascular functions could be the main cause of the haemodynamic instability of patients prone to collapse.

Aged↗

Heart rate variability spectral indices for haemodynamic classification of haemodialysis patients.

The usefulness of spectral indices extracted from the heart rate variability (HRV) in discriminating between hypotension-prone and hypotension-resistant haemodialysis patients was investigated. In 30 patients, classified as hypotension resistant (stable group) or hypotension prone (unstable group), beat-to-beat heart period was measured during haemodialysis sessions terminated without collapses. HRV was analysed in the frequency domain combining classic autoregressive spectral estimation with two eigen decomposition-based techniques: the reduced rank approximation (RRA) of the autocorrelation matrix and the Pisarenko harmonic decomposition (PHD). Five spectral indices were obtained: the ratio between the powers in the LF and HF bands (LF/HF), the same ratio calculated after application of RRA (LF/HFRRA), the frequency of the main oscillatory component of HRV estimated through PHD with a decomposition order equal to 1 (F1) and equal to 2 (F2) and the difference between the frequencies of the two oscillatory components resolved in the latter cas (Fd). The performances of these indices in discriminating between the two groups of patients were evaluated estimating the misclassification probability (Pm) of a Bayesian quadratic classifier. The HRV spectral pattern was markedly different: in the stable patients power was mainly in the low-frequency band, whereas in the unstable group it was mainly in the high-frequency band. The frequency of the main oscillatory component was significantly greater in the unstable group than in the stable one. Spectral indices displayed good discrimination power, increasing with the length of the dialysis interval. Best performances were achieved by LF/HFRRA both over short dialysis periods (Pm approximately 12% over 20 min intervals) and over longer periods (Pm = 3.3% over 160 min); similar results were obtained with Fd over short periods and LF/HF over long periods. Spectral HRV indices demonstrate, therefore, a diagnostic value in discriminating between hypotension-resistant and hypotension-prone patients.

Bayes Theorem↗

Theoretical analysis of complex oscillations in multibranched microvascular networks.

A mathematical model was used to study the origin of complex self-sustained diameter oscillations in multibranched microvascular networks. The model includes three branching levels (order 3, 2, and 1 arterioles) of a microvascular network derived from in vivo observation in the hamster dorsal cutaneous muscle. The main biomechanical aspects covered by the model are (1) the dependence of the elastic and active wall stress on the inner radius and (2) the static and dynamic myogenic response. Simulations on isolated arterioles indicate that self-sustained periodic diameter oscillations may occur at constant transmural pressure. Conversely, simulations on the entire network reveal different oscillatory patterns, including periodic, quasiperiodic, and chaotic fluctuations. Chaos in the model is revealed by the presence of a broad noise-like component in the frequency spectrum and by the sensitivity dependence of model results on small perturbations. Our results suggest that, owing to the intrinsic nonlinearity of the system, a contracting mechanism, such as the myogenic response, may induce different oscillatory patterns. The change from periodic to chaotic oscillations may be a consequence of a modest variation in a parameter (systemic pressure or arterial resistance) not necessarily related to pathophysiological conditions. Accordingly, our in vivo observations in the skeletal muscle showed that in some instances arteriolar vasomotion is converted from regular to highly irregular patterns in basal conditions. Vasomotion is found to affect mean blood flow compared with the nonoscillatory steady state. Chaotic oscillations tend to maintain a constant ratio of blood flows entering into bifurcation vessels, whereas periodic vasomotion determines a different flow distribution at branches.

Animals↗

Parametric analysis of heart rate variability during hemodialysis.

The problem of evaluating short-term autonomic response to hypovolemia in patients under chronic hemodialysis treatment is considered. Power spectra of the beat-to-beat heart rate variability were evaluated during the dialysis treatment in twenty hemodynamically stable and unstable patients, using a parametric technique. The autoregressive model coefficients were calculated by the modified covariance method, while model order was selected according to the minimum description length criterion. Reported results demonstrate that stable and unstable patients present markedly different spectral patterns. The efficiency of the compensatory response to hemodialysis-induced hypovolemia was evaluated through the ratio between the powers in LF and HF bands. Stable patients exhibit a LF/HF ratio greater than one with large fluctuations over the whole dialysis session. In contrast, all the unstable patients are characterized by a value of LF/HF lower than one and with a reduced time variability. This result suggests that the hemodynamic instability of the hypotension-prone patients may be due to a deficiency in the short-term compensatory response to the hemodialysis-induced hypovolemia.

Algorithms↗

Modeling of cardiovascular variability using a differential delay equation.

The influence of time delay in the baroreflex control of the heart activity is analyzed by using a simple mathematical model of the short-term pressure regulation. The mean arterial pressure in a Windkessel model is controlled by a nonlinear feedback driving a nonpulsatile model of the cardiac pump in accordance with the steady-state characteristics of the arterial baroreceptor reflex. A pure time delay is placed in the feedback branch to simulate the latent period of the baroreceptor regulation. Because of system nonlinearity model dynamics is found to be highly sensitive to time delay and changes of this parameter within a physiological range cause the model to exhibit different patterns of behavior. For low values of time delay (shorter than 0.5 s) the model remains in a steady state. When time delay is longer than 0.5 s, a Hopf bifurcation is crossed and spontaneous oscillations occur with frequencies in the high-frequency (HF) band. Further increases of time delay above 1.2s cause the oscillations to become more complex, and following the typical Feigenbaum cascade, the system becomes chaotic. In this condition heart rate, and flow show evident variability. The heart rate power spectrum exhibits a peak whose frequency moves from the HF to LF band depending on whether simulated time delay is as short as the vagal-mediated control or long as the sympathetic one.

Baroreflex↗

Velocity profile distribution along an arterial vessel: way to improve detection of stenotic sites.

The influence of an arterial stenosis on the pattern of blood velocity spatial distribution is investigated. The blood velocity field in a human femoral artery in a stenotic state is computed by means of numerical simulation. Four distributions of velocity profiles along the vessel are shown, corresponding to four different instants of the cardiac cycle. The shape of the spatial pattern of the velocity profile is strongly perturbed by the stenosis: disturbances are so clear that an easy, precise localisation of the stenotic site is always possible, whatever instant of the cardiac cycle is considered. The reported results prove that a three-dimensional view of the velocity profile distribution along the vessel best emphasises the relevant haemodynamic information from a diagnostic point of view.

Arterial Occlusive Diseases↗

Hemodynamics of an artery with mild stenosis.

In this study the hemodynamics in the early stages of the atherosclerotic process--when a neointimal hyperplasia or an intimal fibrocellular hypertrophy takes place--is theoretically investigated. A local, slight increase in the wall thickness of a canine femoral artery is simulated using an original two-dimensional mathematical model of arterial hemodynamics and the effects induced on the velocity field by the simulated mild stenosis--only 2% of area reduction--are analysed. The model incorporates: fluid non-linear inertial forces, viscoelastic wall motion, anatomical taper, unsteady flow, pressure propagation and reflections on both the proximal and distal vessel ends. Two different physiological pulsatile flows are considered: a basal flow condition and a light vasodilation state inducing in the vessel segment a limited increase in mean flow (50%). The distribution along the vessel during the cardiac cycle of both the velocity profile and wall shear stress, are shown. The shape of velocity distributions is strongly perturbed by the stenosis and disturbances are clearly evident whatever instant of the cardiac cycle is considered. After vasodilatation, during the phase of systolic deceleration, a vortex circulation appears in the post-stenotic region. The vortex persists for the whole diastolic phase, causing a very strong stress at the arterial wall: wall shear stress in the distal part of the simulated mild stenosis is at least five times the basal value. The reported results provide a coherent explanation of the critical role that hemodynamic factors may play in the early stages of atherogenic process.

Algorithms↗