Aneta Stefanovska

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 state 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 how 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.

Regulation of human cutaneous circulation evaluated by laser Doppler flowmetry, iontophoresis, and spectral analysis: importance of nitric oxide and prostaglandines

Nitric oxide (NO) and prostaglandines (PGs) are important in regulation of vascular tone and blood flow. Their contribution in human cutaneous circulation is still uncertain. We inhibited NO synthesis by infusing N(G)-monomethyl-L-arginine (L-NMMA) in the brachial artery (16 micromol/min for 5 min) and reversed it by intraarterial infusion of L-arginine (40 micromol/min for 7.5 min). PG synthesis was inhibited by the cyclooxygenase inhibitor aspirin (600 mg over 5 min intravenously). Basal cutaneous perfusion and perfusion responses during iontophoresis with the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were recorded by laser Doppler flowmetry (LDF). We performed wavelet transforms of the measured signals. Mean spectral amplitude within the frequency interval from 0.0095 to 1.6 Hz and mean and normalized amplitudes of five intervals around 1, 0.3, 0.1, 0.04, and 0.01 Hz were analysed. The oscillations with frequencies around 1, 0.3, 0.1, and 0.04 Hz are influenced by the heartbeat, the respiration, the intrinsic myogenic activity of vascular smooth muscle, and the neurogenic activity of the vessel wall, respectively. We have previously shown that the oscillation with a frequency around 0.01 Hz is modulated by the vascular endothelium. L-NMMA reduced mean value of the LDF signal by approximately 20% (P = 0.0067). This reduction was reversed by L-arginine. Mean value of the LDF signals during ACh and SNP iontophoresis did not change after infusion of L-NMMA. Aspirin did not affect mean value of the LDF signal or the LDF signal during ACh or SNP iontophoresis. Before interventions the only significant difference between the effects of ACh and SNP was observed in the frequency around 0.01 Hz, where ACh increased normalized amplitude to a greater extent than SNP. L-NMMA abolished this difference, whereas it reappeared after infusion of L-arginine (P = 0.0084). Aspirin did not affect this difference (P = 0.006). We conclude that basal cutaneous blood flow and the endothelial dependency of the oscillation around 0.01 Hz are partly mediated by NO, but not by endogenous PGs. Other aspects of human cutaneous circulation studied are not regulated by NO or PGs.

Physics of the human cardiovascular system

Contemporary measurement techniques permit the non-invasive observation of several cardiovascular functions, both from the central and peripheral points of view. We show that, within one cycle of blood through the cardiovascular system, the same dynamics characterizes heart function as well as blood flow in the capillary bed where cells exchange energy and matter. Analyses of several quite different signals derived from respiration, cardiac function and blood flow, all reveal the existence of five almost periodic frequency components. This result is interpreted as evidence that cardiovascular dynamics is governed by five coupled oscillators. The couplings provide co-ordination among the physiological processes involved, and are essential for efficient cardiovascular function. Understanding the dynamics of a system of five coupled oscillators not only represents a theoretical challenge, but also carries practical implications for diagnosis and for predicting the future behaviour of this life giving system.

Synchronization and modulation in the human cardiorespiratory system

We analyse phase and frequency synchronization in the human cardio-respiratory system. The method for analysis of noisy nonstationary bivariate data is applied to simultaneously measured cardiac and respiratory activity. Short epochs of phase and/or frequency locking between respiratory and cardiac rhythms are detected in healthy relaxed subjects (non-athletes). We reveal that the strength of phase synchronization is inversely related to the extent of respiratory modulation of the heart rate.

Wavelet Phase Coherence Analysis: Application to Skin Temperature and Blood Flow

The technique of wavelet phase coherence analysis is introduced and used to explore relationships between oscillations on blood flow and temperature in the skin of 10 healthy subjects. Their skin temperature and blood flow were continuously recorded: under basal conditions for 30 min; during local cooling of the skin with an ice-pack for 20 min: and 30 min thereafter. The group mean basal skin temperature of 33.4°C was decreased to 29.2°C during the cooling period, and had recovered to 32.1°C by the end of the recording. The wavelet transform was used to obtain the time–frequency content of the two signals, and their coherence. It is shown that cooling increases coherence to a statistically significant extent in two frequency intervals, around 0.007 and 0.1 Hz, suggesting that these oscillatory components are involved in the regulation of skin temperature when cold is applied as a stress.

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 subjects central nervous systems.

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.

The Effects of General Anesthesia on Human Skin Microcirculation Evaluated by Wavelet Transform

BACKGROUND:Time-frequency analysis of the laser Doppler flowmetry signal, using wavelet transform, shows periodic oscillations at five characteristic frequencies related to the heart (0.6–2 Hz), respiration (0.15–0.6 Hz), myogenic activity in the vessel wall (0.052–0.15 Hz), sympathetic activity (0.021–0.052 Hz), and very slow oscillations (0.0095–0.021), which can be modulated by the endothelium-dependent vasodilator acetylcholine. We hypothesized that wavelet transform of laser Doppler flowmetry signals could detect changes in the microcirculation induced by general anesthesia, such as alterations in vasomotion and sympathetic activity. METHODS:Eleven patients undergoing faciomaxillary surgery were included. Skin microcirculation was measured on the lower forearm with laser Doppler flowmetry and iontophoresis with acetylcholine and sodium nitroprusside before and during general anesthesia with propofol, fentanyl, and midazolam. The laser Doppler flowmetry signals were analyzed using wavelet transform. RESULTS:There were significant reductions in spectral amplitudes in the 0.0095–0.021 (P < 0.01), the 0.021–0.052 (P < 0.001), and the 0.052–0.15 Hz frequency interval (P < 0.01) and a significant increase in the 0.15–0.6 Hz frequency interval. General anesthesia had no effect on the difference between acetylcholine and sodium nitroprusside on relative amplitudes in the 0.0095–0.021 Hz frequency interval (P < 0.001). CONCLUSION:General anesthesia reduces the oscillatory components of the perfusion signal related to sympathetic, myogenic activity and the component modulated by the endothelium. However, the iontophoretic data did not reveal a specific effect on the endothelium. The increase in the 0.15–0.6 Hz interval is related to the effect of mechanical ventilation.

Interactions between cardiac, respiratory and EEG-δ oscillations in rats during anaesthesia

We hypothesized that, associated with the state of anaesthesia, characteristic changes exist in both cardio‐respiratory and cerebral oscillator parameters and couplings, perhaps varying with depth of anaesthesia. Electrocardiograms (ECGs), respiration and electroencephalograms (EEGs) were recorded from two groups of 10 rats during the entire course of anaesthesia following the administration of a single bolus of ketamine–xylazine (KX group) or pentobarbital (PB group). The phase dynamics approach was then used to extract the instantaneous frequencies of heart beat, respiration and slow δ‐waves (within 0.5–3.5 Hz). The amplitudes of δ‐ and θ‐waves were analysed by use of a time–frequency representation of the EEG signal within 0.5–7.5 Hz obtained by wavelet transformation, using the Morlet mother wavelet. For the KX group, where slow δ‐waves constituted the dominant spectral component, the Hilbert transform was applied to obtain the instantaneous δ‐frequency. The θ‐activity was spread over too wide a spectral range for its phase to be meaningfully defined. For both agents, we observed two distinct phases of anaesthesia, with a marked increase in θ‐wave activity occurring on passage from a deeper phase of anaesthesia to a shallower one. In other respects, the effects of the two anaesthetics were very different. For KX anaesthesia, the two phases were separated by a marked change in all three instantaneous frequencies: stable, deep, anaesthesia with small frequency variability was followed by a sharp transition to shallow anaesthesia with large frequency variability, lasting until the animal awoke. The transition occurred 16–76 min after injection of the anaesthetic, with simultaneous reduction in the δ‐wave amplitude. For PB anaesthesia, the two epochs were separated by the return of a positive response to the pinch test at 53–94 min, following which it took a further period of 45–70 min for the animal to awaken. δ‐Waves were not apparent at any stage of PB anaesthesia. We applied non‐linear dynamics and information theory to seek evidence of causal relationships between the cardiac, respiratory and slow δ‐oscillations. We demonstrate that, for both groups, respiration drives the cardiac oscillator during deep anaesthesia. During shallow KX anaesthesia the direction either reverses, or the cardio‐respiratory interaction becomes insignificant; in the deep phase, there is a unidirectional deterministic interaction of respiration with slow δ‐oscillations. For PB anaesthesia, the cardio‐respiratory interaction weakens during the second phase but, otherwise, there is no observable change in the interactions. We conclude that non‐linear dynamics and information theory can be used to identify different stages of anaesthesia and the effects of different anaesthetics.

Coupled Oscillatros: Complex But Not Complicated Cardiovascular and Brain Interactions

In coupled nonlinear oscillators approach, the framework that has been used for the studies of cardiovascular and brain oscillations. As background, it describes the human CVS and present results of time-frequency analysis using wavelet transforms of several noninvasive measurements of cardiovascular signals. Studies of neuronal oscillations have been undertaken since the first human electroencephalographic (EEG) recording, and the recent resurgence of interest in neuronal oscillations. It is concluded that interactions occur between the oscillatory processes, both within and between the cardiovascular and the neuronal systems. The strengths and directions of these interactions may be used, in principle, for characterization of the state of the organism as demonstrated here for the case of deep anesthesia.