Biomedical subjects

A Stefanovska

Publications and source records attributed to A Stefanovska.

At least 19 recordsLinked to original sources

PubMed2007

Incipient cardiovascular autonomic imbalance revealed by wavelet analysis of heart rate variability in Type 2 diabetic patients.

AIM: Incipient cardiovascular autonomic imbalance is not readily diagnosed by conventional methods. Spectral analysis of heart rate variability (HRV) by wavelet transform (WT) was used to measure cardiovascular autonomic function in patients with Type 2 diabetes. METHODS: Thirty-two diabetic patients without (D), 26 with cardiovascular autonomic neuropathy (DAN) and 72 control subjects (C) participated. A 30-min HRV time series was analysed by wavelet transformation and four characteristic frequency intervals were defined: I (0.0095-0.021 Hz), II (0.021-0.052 Hz), III (0.052-0.145 Hz) and IV (0.145-0.6 Hz). RESULTS: When compared with C, in both D and DAN the normalized power and amplitude of interval II were increased and of interval IV decreased, resulting in a significantly higher II/IV ratio. Furthermore, in DAN the normalized power and amplitude of interval I were increased and of interval III decreased when compared with the D and C groups. The diabetic patients were divided in two equal subgroups according to HbA(1c) < 8.0% and >or= 8.0%. In the subgroup with HbA(1c) >or= 8.0%, normalized power in interval II was significantly higher and in interval IV significantly lower than in the subgroup with HbA(1c) < 8.0%. In D, but not in DAN patients prescribed ACE inhibitors, the absolute amplitude and power of oscillations were significantly higher than in patients not taking ACE inhibitor therapy. CONCLUSIONS: Patients with diabetes have increased sympathetic and decreased parasympathetic cardiac activity regardless of the presence of autonomic neuropathy. Glycaemic control and treatment with ACE inhibitors may favourably influence HRV in diabetic patients without autonomic neuropathy.

Aged↗

PubMed2005

Nonlinear statistical modeling and model discovery for cardiorespiratory data.

We present a Bayesian dynamical inference method for characterizing cardiorespiratory (CR) dynamics in humans by inverse modeling from blood pressure time-series data. The technique is applicable to a broad range of stochastic dynamical models and can be implemented without severe computational demands. A simple nonlinear dynamical model is found that describes a measured blood pressure time series in the primary frequency band of the CR dynamics. The accuracy of the method is investigated using model-generated data with parameters close to the parameters inferred in the experiment. The connection of the inferred model to a well-known beat-to-beat model of the baroreflex is discussed.

Algorithms↗

PubMed2005

Inference of a nonlinear stochastic model of the cardiorespiratory interaction.

We reconstruct a nonlinear stochastic model of the cardiorespiratory interaction in terms of a set of polynomial basis functions representing the nonlinear force governing system oscillations. The strength and direction of coupling and noise intensity are simultaneously inferred from a univariate blood pressure signal. Our new inference technique does not require extensive global optimization, and it is applicable to a wide range of complex dynamical systems subject to noise.

Blood Pressure↗

PubMed2004

Skin blood flow in the upper and lower extremities of diabetic patients with and without autonomic neuropathy.

BACKGROUND: Microvascular blood flow in the human skin is subject to rhythmic variations reflecting the influence of heartbeat, respiration, intrinsic myogenic activity, neurogenic factors and endothelial activity. The aim of our study was to test the hypothesis that basal skin blood flow (BSBF) and its dynamic components differ (1) among diabetic patients without autonomic neuropathy and with it and healthy control subjects, and (2) among the upper and lower extremities. PATIENTS AND METHODS: BSBF at four recording sites with predominantly nutritive capillary circulation (right and left caput ulnae, right and left medial malleolus) was measured by laser Doppler flowmetry in 25 diabetic patients without cardiovascular autonomic neuropathy (D), 18 neuropathic diabetic patients (DAN) and 36 healthy controls (C). Wavelet transform was applied to the laser Doppler signal. RESULTS: In absolute terms, mean flow, mean amplitude of the total spectrum and mean amplitudes at all frequency intervals were highest in C, followed by DAN and lowest in D. However, these differences were statistically significant only in the left arm. Within all three groups, mean flow and spectral amplitudes were significantly higher in the arms than in the legs, besides there was a significant difference between the two arms in D. CONCLUSION: We have confirmed the differences in BSBF among D, DAN and C, and demonstrated differences among the four recording sites which have not been previously described. The latter indicates an uneven progression of autonomic neuropathy and allows for speculation that the left arm is the latest to be affected.

Aged↗

PubMed2001

The cardiovascular system as coupled oscillators?

Based on physiological knowledge, and on an analysis of signals related to its dynamics, we propose a model of the cardiovascular system. It consists of coupled oscillators. Each of them describes one of the subsystems involved in the regulation of one passage of blood through the circulatory system. The flow of blood through the system of closed tubes-the blood vessels-is described by wave equations.

Blood Pressure↗

PubMed2001

Modelling couplings among the oscillators of the cardiovascular system.

A mathematical model of the cardiovascular system is simulated numerically. The basic unit in the model is an oscillator that possesses a structural stability and robustness motivated by physiological understanding and by the analysis of measured time series. Oscillators with linear couplings are found to reproduce the main characteristic features of the experimentally obtained spectra. To explain the variability of cardiac and respiratory frequencies, however, it is essential to take into account the rest of the system, i.e. to consider the effect of noise. It is found that the addition of noise also results in epochs of synchronization, as observed experimentally. Preliminary analysis suggests that there is a mixture of linear and parametric couplings, but that the linear coupling seems to dominate.

Artifacts↗

PubMed2000

Reversible transitions between synchronization states of the cardiorespiratory system.

Phase synchronization between cardiac and respiratory oscillations is investigated during anesthesia in rats. Synchrograms and time evolution of synchronization indices are used to show that the system passes reversibly through a sequence of different phase-synchronized states as the anesthesia level changes, indicating that it can undergo phase transitionlike phenomena. It appears that the synchronization state may be used to characterize the depth of anesthesia.

Anesthesia↗

PubMed2000

Spectral components of heart rate variability determined by wavelet analysis.

Spectral components of heart rate variability (HRV) are determined in the time-frequency domain using a wavelet transform. Based on the finer estimation of low-frequency content enabled by the logarithmic resolution of the wavelet transform, corrections of spectral intervals, already defined by Fourier and model based methods, are proposed. The characteristic peaks between 0.0095 and 0.6 Hz are traced in time and four spectral intervals are defined, I (0.0095-0.021 Hz), II (0.021-0.052 Hz), III (0.052-0.145 Hz) and IV (0.145-0.6 Hz), within which peaks are located for all subjects included. These intervals are shown to be invariant regardless of the age and the state of the system. We also show that the frequency and power of the spectral components are related to age, AMI and particularly to type II diabetes mellitus.

Adult↗

PubMed2000

The contribution of lumbar sympathetic neurones activity to rat's skin blood flow oscillations.

Skin blood flow on the rat's paws using laser Doppler flowmeter, electrical activity of the heart (ECG) and respiration were measured simultaneously. The signals were recorded for 20 minutes, both before and after denervation, at core temperature 37 degrees C and 38.5 degrees C, that was maintained constant during the recordings. Spinal nerve fibres, at the level L3-L4, were transected. Experiments were performed on 15 adult Wistar rats under general anaesthesia. The oscillations in the measured signals were analysed in the time-frequency domain using wavelet transform. On the frequency region from 0.7 Hz to 5 Hz two characteristic peaks were observed in the skin blood flow spectrum. They correspond to the main peaks in the spectra of the ECG (around 3.3 Hz) and respiration (around 1.3 Hz). Several additional peaks were observed in the low frequency region, from 0.01 to 0.7 Hz, in all measured signals. In this frequency region the relative energy contribution of the blood flow oscillations decreased after denervation only in the denervated left hind paw. This difference was not statistically significant at 37 degrees C (p=0.098, Kruskal-Wallis test) but became statistically significant at 38.5 degrees C (p=0.017). Relative energy contribution of the low frequency region, from 0.01 to 0.7 Hz, decreased 2.5-fold in the blood flow of the denervated paw. Within this region the relative energy contribution decreased significantly in two intervals, from 0.01 to 0.08 Hz and from 0.08 to 0.2 Hz (p=0.023). In the higher frequency region, from 0.7 to 5 Hz, o statistically significant differences were obtained in any paws when compared before and after denervation at the same core temperature. We conclude that the activity of lumbar sympathetic neurones contributes to low frequency skin blood flow oscillations.

Animals↗

PubMed1999

Oscillations in the human cutaneous blood perfusion signal modified by endothelium-dependent and endothelium-independent vasodilators.

The purpose of the present study was to compare the effects of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilators on the oscillatory components of the cutaneous blood perfusion signals in humans. The unstimulated basal blood perfusion and the blood perfusion during iontophoretically delivered ACh and SNP were measured using laser Doppler flowmetry (LDF). The wavelet transform was calculated before spectral analysis of the measured signals. In the frequency interval from 0.0095 to 1.6 Hz the LDF signal consists of oscillations with five different characteristic frequencies. In addition to the cardiac (1 Hz) and respiratory (0.3 Hz) rhythms, three other oscillations in the regions around 0.1, 0.04, and 0.01 Hz were detected. The oscillations with the different frequencies were observed in unstimulated blood flow and also during stimulation with ACh and SNP. Compared to the unstimulated blood flow, both ACh and SNP increased the mean amplitude of the total spectrum (P < 0. 005 for both substances). The only significant difference between the effects of ACh and SNP was observed in the amplitude of oscillations with the frequency of around 0.01 Hz. ACh increased the absolute amplitude of this frequency to a greater extent than SNP in athletes (P = 0.03), whereas only a trend was observed in controls (P = 0.2). The relative amplitude, defined as the ratio between the absolute amplitude of a particular frequency interval and the mean amplitude of the total spectrum, was also higher for ACh compared to SNP both in controls (P = 0.008) and in athletes (P = 0.004), only for oscillations with the frequency of around 0.01 Hz. We conclude that ACh selectively influences the oscillatory component of around 0.01 Hz in the cutaneous blood perfusion signal to a greater extent than SNP. This finding indicates that endothelium-mediated vasodilatation is manifested as oscillations with a repetition time of approximately 1 min. The mechanisms for the endothelial dependency of this frequency remain to be elucidated. Our data indicate that spectral analysis based on wavelet transform of the cutaneous perfusion signal can be used clinically to investigate endothelial function. The described noninvasive method might be used to evaluate endothelial function for research, for diagnostic purposes, and maybe also to assess effects of therapy in cardiovascular diseases.

Acetylcholine↗

PubMed1999

Wavelet analysis of oscillations in the peripheral blood circulation measured by laser Doppler technique.

The wavelet transform technique, a time-frequency method with logarithmic frequency resolution, was used to analyze oscillations in human peripheral blood flow measured by laser Doppler flowmetry. The oscillations extended over a wide frequency scale and their periods varied in time. Within the frequency range studied, 0.0095-1.6 Hz, five characteristic oscillations were revealed, arising from both local and central regulatory mechanisms. After the insertion of endothelium-dependent and endothelium-independent vasodilators the spectra of blood flow markedly differed in the frequency interval 0.0095-0.02 Hz. In this way it was demonstrated that endothelial activity is a rhythmic process that contributes to oscillations in blood flow with a characteristic frequency of around 0.01 Hz. The study illustrates the potential of laser Doppler flowmetry combined with dynamical systems analysis for studies of both the micro- and macroscopic mechanisms of blood flow regulation in vivo.

Acetylcholine↗

PubMed1999

Linear and nonlinear analysis of blood flow in healthy subjects and in subjects with Raynaud's phenomenon.

The paper presents analyses of the dynamics contained in the blood flow signals measured on healthy subjects and on subjects with primary Raynaud's phenomenon. Different signal processing methods are presented and discussed. The dynamics was evaluated in the time and frequency domains and in phase space. Additionally, changes in the basal value during temperature provocation were studied using multiresolution analysis. The analyses demonstrate differences between the blood flow dynamics in healthy subjects and subjects with Raynaud's phenomenon. Moreover, the observed decrease in the amplitude of oscillation in regions approximately 0.04 Hz and approximately 0.1 Hz suggests an impairment in the neurogenic and the myogenic regulation of the blood flow. The administration of nifedipine in subjects with Raynaud's phenomenon results in an increase in the basal value and in the amplitude of the blood flow component oscillating with the heart rate. However, it does not restore the dynamics to that found in healthy subjects.

Adolescent↗

PubMed1998

Nonlinear dynamics of the blood flow studied by Lyapunov exponents.

In order to gain an insight into the dynamics of the cardiovascular system throughout which the blood circulates, the signals measured from peripheral blood flow in humans were analyzed by calculating the Lyapunov exponents. Over a wide range of algorithm parameters, paired values of both the global and the local Lyapunov exponents were obtained, and at least one exponent equaled zero within the calculation error. This may be an indication of the deterministic nature and finite number of degrees of freedom of the cardiovascular system governing the blood-flow dynamics on a time scale of minutes. A difference was observed in the Lyapunov dimension of controls and athletes.

Algorithms↗

PubMed1998

Wavelet-based analysis of human blood-flow dynamics.

To analyze signals measured from human blood flow in the time-frequency domain, we used the wavelet transform which gives good time resolution for high-frequency components and good frequency resolution for low-frequency components. Five characteristic frequency peaks, corresponding to five almost periodic rhythmic activities, were found on the time scale of minutes. These oscillations were characterized by time and spatial invariant measures. The potential of this approach in studying the blood-flow dynamics was illustrated by revealing differences between the groups of control subjects and athletes.

Cardiovascular Physiological Phenomena↗

PubMed1998

Spectral analysis of the laser Doppler perfusion signal in human skin before and after exercise.

Spectral analysis based on wavelet transformation of the periodic oscillations of the cutaneous laser Doppler flowmetry (LDF) signal was used to analyze exercise-induced changes in flow motion in humans. The measurements were performed on the forearm skin in nine healthy, less-trained subjects before and after exercise. Periodic oscillations with frequencies of around 1, 0.3, 0.1, and 0.04 Hz were demonstrated, which are proposed to represent the influence of heart beat, respiration, intrinsic myogenic activity, and the neurogenic factors, respectively, on cutaneous blood flow. We also demonstrated oscillations with a frequency of around 0.01 Hz both before and after exercise. The mean spectral amplitude in the frequency range from 0.0095 to 2.3 Hz increased twofold (P = 0.004) in response to exercise. This increase results from a significant increase in the amplitude of oscillations of around 1, 0.3, and 0.1 Hz. The amplitude of oscillations of around 1 and 0.3 Hz increased onefold in response to exercise (P = 0.02 for both frequencies), whereas the amplitude of oscillations of around 0.1 Hz increased threefold (P = 0.008). Furthermore, to evaluate relative changes of each particular oscillation in response to exercise, the absolute amplitude of each frequency interval was divided by the mean spectral amplitude. In this way, the relative contribution of oscillations of around 0.01 and 0.04 Hz were shown to decrease significantly following exercise (P = 0.008 and P = 0.004, respectively). The relative contribution of the oscillations of around 0.1 Hz increased, although not statistically significant (P = 0.08), while the relative contribution of the oscillations of around 0.3 and 1 Hz to the total flow motion remained unchanged in response to exercise (P = 0.84 and P = 0.95, respectively). These findings indicate an increased contribution of the oscillations of around 0.1 Hz to the regulation of the cutaneous blood flow following exercise, whereas oscillations of around 0.04 and 0.01 Hz contribute less. We conclude that spectral analysis using a wavelet transformation of the LDF signal is a valuable tool for use in the evaluation of exercise-induced changes in the dynamics of cutaneous microvascular blood flow, but further studies are necessary to clarify the physiological origin of these oscillations.

Exercise↗

PubMed1998

Enhanced endothelium-dependent vasodilatation in human skin vasculature induced by physical conditioning.

Functional alterations to the endothelial cells of the vascular system may contribute to the improved circulatory performance induced by physical conditioning. We evaluated microvascular reactivity to iontophoretic application of acetylcholine (ACh) and sodium nitroprusside (SNP) through the skin and blood perfusion measurements in the same area using laser Doppler flowmetry. Whereas ACh acts on smooth muscle cells of the vascular system via the production of vasodilator substances from the endothelium, SNP is an endothelium-independent vasodilator acting on vascular smooth muscle cells directly. The study was performed using two groups of subjects with different levels of aerobic endurance, long distance runners competing at national level (n = 9) and controls (n = 9). The subjects were tested for 40 min on a treadmill before and after an exercise test at 80% of their maximal oxygen uptake. During stimulation by ACh cutaneous perfusion increased to a higher level in the athletes than in the controls (overall P<0.05), whereas an acute period of exercise abolished this difference (overall P>0.6). There was no significant difference between the athletes and the controls with respect to the SNP-induced increase in cutaneous perfusion either before (P>0.9) or after (P>0.9) exercise. The higher cutaneous perfusion responses to stimulation with ACh in the athletes than in the controls may support the hypothesis that regular exercise modifies the responsiveness of the cutaneous endothelium. The difference in ACh-induced perfusion and in unstimulated forearm perfusion between the two groups was present only at rest. This finding indicated that mechanisms were introduced during exercise, which compensated for the lower endothelial sensitivity to stimulation in the controls at rest.

Acetylcholine↗

PubMed1996

Therapeutic neural effects of electrical stimulation.

The use of a functional neuromuscular stimulation (FNS) device can have therapeutic effects that persist when the device is not in use. Clinicians have reported changes in both voluntary and electrically assisted neuromuscular function and improvements in the condition of soft tissue. Motor recovery has been observed in people with incomplete spinal cord injury, stroke, or traumatic brain injury after the use of motor prostheses. Improvement in voluntary dorsiflexion and overall gait pattern has been reported both in the short term (several hours) and permanently. Electrical stimulation of skin over flexor muscles in the upper limb produced substantial reductions for up to 1 h in the severity of spasticity in brain-injured subjects, as measured by the change in torque generation during ramp-and-hold muscle stretch. There was typically an aggravation of the severity of spasticity when surface stimulation reached intensities sufficient to also excite muscle. Animals were trained to alter the size of the H-reflex to obtain a reward. The plasticity that underlies this operantly conditioned H-reflex change includes changes in the spinal cord itself. Comparable changes appear to occur with acquisition of certain motor skills. Current studies are exploring such changes in humans and animals with spinal cord injuries with the goal of using conditioning methods to assess function after injury and to promote and guide recovery of function. A better understanding of the mechanisms of neural plasticity, achieved through human and animal studies, may help us to design and implement FNS systems that have the potential to produce beneficial changes in the subject's central nervous systems.

Animals↗

PubMed1993

Treatment of chronic wounds by means of electric and electromagnetic fields. Part 2. Value of FES parameters for pressure sore treatment.

Subjects with spinal cord injury are often distressed by pressure sores, which usually appear after prolonged pressure (wheelchair, bed) across the soft tissue which has already lost sensibility and has diminished microcirculation. The healing ability and its dynamics depend on the state of the subject's overall health. Consequently, evaluation of a particular treatment requires careful consideration of as many as possible of the parameters relevant to healing and an adequate criterion for assessing the state of the pressure sore. Bearing in mind these two circumstances, the results of a multicentre clinical study are analysed. The aim of the study was to test two hypotheses: first that healing is faster when sores are also treated by electric currents (ECs) (in addition to conventional treatment); and secondly that there exist differences in the efficiency of the treatment if direct or low-frequency pulsed currents (FES parameters) are applied. The data analysed show that pressure sores are likely to heal twice as fast when treated with low-frequency pulsed currents. EC seems to improve the healing rate in cases where the natural healing mechanisms of the body are not sufficient (chronic wounds, older subjects).

Adult↗