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Biomedical subjects

Aneta Stefanovska

Publications and source records attributed to Aneta Stefanovska.

13 recordsLinked to original sources

Low-frequency oscillations of the laser Doppler perfusion signal in human skin.

Spectral analysis of the laser Doppler flow (LDF) signal in the frequency interval from 0.0095-2.0 Hz reveals blood flow oscillations with frequencies around 1.0, 0.3, 0.1, 0.04 and 0.01 Hz. The heartbeat, the respiration, the intrinsic myogenic activity of vascular smooth muscle, the neurogenic activity of the vessel wall and the vascular endothelium influence these oscillations, respectively. The first aim of this study was to investigate if a slow oscillatory component could be detected in the frequency area below 0.0095 Hz of the human cutaneous blood perfusion signal. Unstimulated basal blood skin perfusion and enhanced perfusion during iontophoresis with the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were measured in healthy male volunteers and the wavelet transform was computed. A low-frequency oscillation between 0.005 and 0.0095 Hz was found both during basal conditions and during iontophoresis with ACh and SNP. Iontophoresis with ACh increased the normalized amplitude to a greater extent than SNP (P = 0.001) indicating modulation by the vascular endothelium. To gain further insight into the mechanisms for this endothelium dependency, we inhibited nitric oxide (NO) synthesis with N(G)-monomethyl-L-arginine (L-NMMA) and prostaglandin (PG) synthesis by aspirin. L-NMMA did not affect the increased response to ACh vs. SNP iontophoresis in the 0.005-0.0095-Hz interval (P = 0.006) but abolished the difference in the 0.0095-0.021-Hz interval (P = 0.97). Aspirin did not affect the difference in response to ACh and SNP in either of the two frequency intervals. Thus, other endothelial mechanisms, such as endothelium-derived hyperpolarizing factor (EDHF), might be involved in the regulation of this sixth frequency interval (0.005-0.0095 Hz).

Acetylcholine↗

Macro- and microcirculation in the lower extremities--possible relationship.

AIMS: Impaired blood supply is a significant risk factor for diabetic foot ulceration and gangrene. A possible relationship between peripheral macroangiopathy and the spectral components of microvascular skin blood flow in the lower extremities was tested in diabetic patients (DP) and non-diabetic subjects (C). PATIENTS AND METHODS: Basal skin blood flow (BSBF) was recorded for 30min at the right and left medial malleolus (predominantly nutritive capillary circulation) by laser Doppler flowmetry in 64 DP and 31 C. Its oscillatory components were analyzed using wavelet transform. Peripheral arterial obliterative disease (PAOD) was defined according to ankle/brachial index (ABI): PAOD+ (ABI<0.9: 21 DP, 12 C), PAOD- (ABI 0.91-1.3: 43 DP, 19 C). RESULTS: No statistically significant differences in BSBF and its oscillatory components were observed between PAOD+ and PAOD-, neither in DP nor in C. In DP, the spectral component of microvascular flow associated with endothelial activity was in significant positive correlation with systolic pressures on brachial and dorsal pedal artery (p=0.001 and 0.010, respectively). CONCLUSIONS: These results indicate that mean BSBF and its oscillatory components do not change with diabetic PAOD; however there is a strong correlation between systolic pressure and the oscillatory components of BSBF related to endothelial activity manifested in the frequency interval 0.0095-0.02Hz.

Aged↗

Left-right asymmetry of the facial microvascular control.

Facial blood flow and temperature were significantly higher on the right side of the forehead compared to the left. This asymmetry implies that the hemispheric autonomic control of the face differs and could influence the expression of emotion.

Adult↗

Human skin microcirculation after brachial plexus block evaluated by wavelet transform of the laser Doppler flowmetry signal.

BACKGROUND: The skin microcirculation may be evaluated noninvasively by laser Doppler flowmetry and iontophoresis with acetylcholine and sodium nitroprusside. Wavelet transform of the perfusion signal shows periodic oscillations of five characteristic frequencies in the interval 0.0095-1.6 Hz. The aim of the current study was to investigate alterations in skin microcirculation induced by brachial plexus block, with emphasis on the periodic oscillations. METHODS: Healthy nonsmokers undergoing hand surgery (n = 13) were anesthetized with brachial plexus block, using bupivacaine, lidocaine, and epinephrine. Skin microcirculation was evaluated by laser Doppler flowmetry and iontophoresis with acetylcholine and sodium nitroprusside before and after brachial plexus block. Wavelet transform of the perfusion signal was performed. As a control group, 10 healthy nonsmokers were included. RESULTS: In the anesthetized arm, skin perfusion after brachial plexus block increased from 19 (12-30) to 24 (14-39) arbitrary units (P < 0.01). A significant increase was also seen in the contralateral arm from 17 (14-32) to 20 (14-42) arbitrary units (P < 0.01). After brachial plexus block, spectral analysis revealed a significant reduction in relative amplitude of the oscillatory components within the 0.0095- to 0.021- (P < 0.001) and 0.021- to 0.052-Hz (P < 0.001) intervals in the anesthetized arm. CONCLUSION: Alterations in skin microcirculation induced by brachial plexus block can be evaluated by wavelet transform of the laser Doppler flowmetry signal. Brachial plexus block reduces the oscillatory components within the 0.0095- to 0.021- and 0.021- to 0.052-Hz intervals of the perfusion signal. These alterations are related to inhibition of sympathetic activity and a possible impairment of endothelial function.

Acetylcholine↗

Lyapunov exponents of laser Doppler flowmetry signals in healthy and type 1 diabetic subjects.

The skin of diabetic subjects presents abnormalities in capillary blood flow and its regulation, often leading to the generation of plantar ulcers. In order to gain insight into this pathology for type 1 diabetic patients, Lyapunov exponents (LEs) of signals reflecting microvascular perfusion--laser Doppler flowmetry (LDF) signals--are calculated. The algorithm to compute LEs is first validated on simulated data and LDF surrogates. Then, LDF signals recorded at rest and during the application of local and progressive pressure of 11.1 Pa/s are processed. The exponents appear in pairs and are different for healthy and type 1 diabetic subjects at rest; P = 0.0556 for the 7th, 8th, and 9th LEs. Furthermore, progressive pressure has also a distinct effect on LEs. The difference is more pronounced for diabetic patients, for whom P = 0.0625 for the four LEs of highest absolute value. Because these differences arise from abnormalities in microvascular blood flow, they may help to explain the high prevalence of type 1 diabetic patients developing foot ulcers.

Animals↗

Nonlinear cardio-respiratory interactions revealed by time-phase bispectral analysis.

Bispectral analysis based on high order statistics, introduced recently as a technique for revealing time-phase relationships among interacting noisy oscillators, has been used to study the nature of the coupling between cardiac and respiratory activity. Univariate blood flow signals recorded simultaneously by laser-Doppler flowmetry on both legs and arms were analysed. Coupling between cardiac and respiratory activity was also checked by use of bivariate data and computation of the cross-bispectrum between the ECG and respiratory signals. Measurements were made on six healthy males aged 25-27 years. Recordings were taken during spontaneous breathing (20 min), and during paced respiration at frequencies both lower and higher than that of spontaneous respiration (either two or three recordings with a constant frequency in the interval between 0.09 and 0.35 Hz). At each paced frequency recordings were taken for 12 min. It was confirmed that the dynamics of blood flow can usefully be considered in terms of coupled oscillators, and demonstrated that interactions between the cardiac and respiratory processes are weak and time-varying, and that they can be nonlinear. Nonlinear coupling was revealed to exist during both spontaneous and paced respiration. When present, it was detected in all four blood flow signals and in the cross-bispectrum between the ECG and respiratory signal. The episodes with nonlinear coupling were detected in 11 out of 22 recordings and lasted between 19 s in the case of high frequency (0.34 Hz) and 106 s in the case of low frequency paced respiration (0.11 Hz).

Adult↗

Wavelet analysis of blood flow dynamics: effect on the individual oscillatory components of iontophoresis with pharmacologically neutral electrolytes.

Iontophoresis currents are used in the transcutaneous delivery of vasoactive substances for noninvasive assessment of skin vascular properties. The blood flow rate can be recorded by laser Doppler flowmetry (LDF), its average value and the amplitudes of its oscillatory components being used to evaluate the effect of the drugs. Because non-drug-specific, current-induced, vasodilation could confound the interpretation of the response, we have investigated the effect of currents of both polarities on the spectral components of the LDF signal in the absence of vasoactive substances. It was recorded for healthy volunteers with both high conductance (5 mol/l NaCl) and low conductance (deionized water) electrolytes. The oscillatory components were analysed by wavelet transform within 0.0095-1.6 Hz, divided into five sub-intervals. Only cathodal iontophoresis with deionized water increased the oscillatory energy and amplitude. It did so at all frequencies, but none of the sub-intervals associated with vasodilation (0.0095-0.145 Hz) was selectively affected compared to the others.

Adult↗

Role of transdermal potential difference during iontophoretic drug delivery.

Potential differences have been measured during transdermal iontophoresis in order to establish the effect of voltage, as opposed to current, on cutaneous blood flow. It is known that, even in the absence of drugs, the iontophoresis current can sometimes produce increased blood flow. The role of voltage in this process is studied through single-ended measurements (between electrode and body) of the potential difference during iontophoresis with 100-microA, 20-s current pulses through deionized water, saturated 20.4% NaCl solution, 1% acetylcholine, and 1% sodium nitroprusside. It is found that the voltage needed to deliver the current varied by orders of magnitudes less than the differences in the conductance of these different electrolytes, and it is concluded that, at least for the present current protocol, the voltage as such is not an important factor in increasing the blood flow.

Acetylcholine↗

Time-phase bispectral analysis.

Bispectral analysis, a technique based on high-order statistics, is extended to encompass time dependence for the case of coupled nonlinear oscillators. It is applicable to univariate as well as to multivariate data obtained, respectively, from one or more of the oscillators. It is demonstrated for a generic model of interacting systems whose basic units are the Poincaré oscillators. Their frequency and phase relationships are explored for different coupling strengths, both with and without Gaussian noise. The distinctions between additive linear or quadratic, and parametric (frequency modulated), interactions in the presence of noise are illustrated.

Journal Article↗

Enhanced endothelial activity reflected in cutaneous blood flow oscillations of athletes.

Functional alterations of vascular endothelial cells may be evaluated by analysing differences in effects of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilators. We evaluated whether a dynamic approach using spectral analysis of the blood flow signal, resulting from the cutaneous red cell flux and recorded by the technique of laser Doppler flowmetry (LDF), can detect higher endothelial responsiveness in trained versus less trained individuals. There was a 1.6 times higher ACh-induced cutaneous perfusion in athletes than in controls ( P<0.05), both when evaluated as a mean value of the LDF signal or as the amplitudes of its spectral components. In the frequency interval from 0.009 to 1.6 Hz, ACh induced a 1.6 times higher average spectral amplitude ( P<0.01) in athletes compared with controls. ACh also induced a 1.6 times higher absolute spectral amplitude of the oscillator at around 0.01 Hz ( P<0.05) in the athletes compared with the controls, whereas the endothelial oscillation at around 0.01 Hz during basal unstimulated perfusion was 1.5 times higher ( P<0.01). There were no significant differences in absolute or relative amplitude during iontophoresis with SNP. These results indicate that athletes have higher endothelial activity than less trained individuals.

Adult↗

Direction of coupling from phases of interacting oscillators: an information-theoretic approach.

A directionality index based on conditional mutual information is proposed for application to the instantaneous phases of weakly coupled oscillators. Its abilities to distinguish unidirectional from bidirectional coupling, as well as to reveal and quantify asymmetry in bidirectional coupling, are demonstrated using numerical examples of quasiperiodic, chaotic, and noisy oscillators, as well as real human cardiorespiratory data.

Journal Article↗

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.

Acetylcholine↗

Involvement of sympathetic nerve activity in skin blood flow oscillations in humans.

We have used the wavelet transform to evaluate the time-frequency content of laser-Doppler flowmetry (LDF) signals measured simultaneously on the surfaces of free microvascular flaps deprived of sympathetic nerve activity (SNA), and on adjacent intact skin, in humans. It was thereby possible to determine the frequency interval within which SNA manifests itself in peripheral blood flow oscillations. The frequency interval from 0.0095 to 2 Hz was examined and was divided into five subintervals: I, approximately 0.01 Hz; II, approximately 0.04 Hz; III, approximately 0.1 Hz; IV, approximately 0.3 Hz; and V, approximately 1 Hz. The average value of the LDF signal in the time domain as well as the mean amplitude and total power in the interval from 0.0095 to 2 Hz and amplitude and power within each of the five subintervals were significantly lower for signals measured on the free flap (P < 0.002). The normalized spectral amplitude and power in the free flap were significantly lower in only two intervals: I, from 0.0095 to 0.021 Hz; and II, from 0.021 to 0.052 Hz (P < 0.05); thus indicating that SNA is manifested in at least one of these frequency intervals. Because interval I has recently been shown to be the result of vascular endothelial activity, we conclude that we have identified SNA as influencing blood flow oscillations in normal tissues with repetition times of 20-50 s or frequencies of 0.02-0.05 Hz.

Adrenergic Fibers↗