Role of transdermal potential difference during intophoretic 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-/spl mu/A, 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

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

Cardiovascular oscillations:in search of a nonlinear parametric model

We suggest a fresh approach to the modeling of the human cardiovascular system. Taking advantage of a new Bayesian inference technique, able to deal with stochastic nonlinear systems, we show that one can estimate parameters for models of the cardiovascular system directly from measured time series. We present preliminary results of inference of parameters of a model of coupled oscillators from measured cardiovascular data addressing cardiorespiratory interaction. We argue that the inference technique offers a very promising tool for the modeling, able to contribute significantly towards the solution of a long standing challenge -- development of new diagnostic techniques based on noninvasive measurements

Singularities in far-from-equilibrium distributions at finite noise intensities

How to find the (strongly non-Boltzmann) distribution in a far-from-equilibrium system is a problem of long standing. It appears in many different contexts, with topical examples including stochastic resonance and Brownian ratchets. One of the most promising approaches to the problem is through asymptotic analysis of the Fokker-Planck equation in the limit of small noise intensity. In simulations and experiments on real systems, however, the noise intensity is necessarily finite. Corrections to allow for finite noise intensity have recently been introduced for the particular case of escape. We are currently investigating the non-equilibrium distribution over the whole of phase space, for two model systems: the periodically driven, overdamped, Duffing oscillator and the inverted van der Pol oscillator. A modified Monte Carlo technique is being applied to investigate the limit of very small noise intensities. The next-to-leading order of approximation of the solution of the Fokker-Planck equation is used to compare the numerical results with the theory. We show, in particular, how changes in the non-equilibrium probability distribution induced by finite noise intensity are linked to an observable modification in the pattern of optimal paths. The numerical observations are in good agreement with theory

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