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Comparative investigations of aspirin and indomethacin effects on blood flow in the vascular bed of skeletal muscles at rest and during muscle contractions in dogs and cats.

The effecs of two different inhibitors of prostaglandin synthesis--aspirin and indomethacin--on the blood flow in the vascular bed of the hindleg of vagotomized animals were studied before, during and after muscular activity of this limb. The responses of resistance and capacitance vessels were recorded simultaneously. Muscular contractions were evoked stimulating electrically (4 impulses/second) the peripheral part of the sciatic nerve. It was found that both inhibitors reduced exercise hyperaemia and postexercise hyperaemia. The response of the capacitance vessels was also reduced during muscular contractions. The obtained results confirmed that endogenous prostaglandins participate in the vascular response during exercise in the precapillary and postcapillary sections of microcirculation in the muscles. The particularly important effect of aspirin on postexercise hyperaemia in dogs in relation to cats is stressed.

Animals↗

Electrical detection of DNA hybridization: three extraction techniques based on interdigitated Al/Al2O3 capacitors.

Based on interdigitated aluminum electrodes covered with Al(2)O(3) and silver precipitation via biotin-antibody coupled gold nano-labels as signal enhancement, three complementary electrical methods were used and compared to detect the hybridization of target DNA for concentrations down to the 50 pM of a PCR product from cytochrome P450 2b2 gene. Human hepatic cytochrome P450 (CYP) enzymes participate in detoxification metabolism of xenobiotics. Therefore, determination of mutational status of P450 gene in a patient could have a significant impact on the choice of a medical treatment. Our three electrical extraction procedures are performed on the same interdigitated capacitive sensor lying on a passivated silicon substrate and consist in the measurement of respectively the low-frequency inter-electrodes capacitance, the high-frequency self-resonance frequency, and the equivalent MOS capacitance between the short-circuited electrodes and the backside metallization of the silicon substrate. This study is the first of its kind as it opens the way for correlation studies and noise reduction techniques based on multiple electrical measurements of the same DNA hybridization event with a single sensor.

Aluminum↗

Electric circuit model for electrical field flow fractionation.

In electrical field flow fractionation (EFFF or ElFFF), an electric potential is applied across a narrow gap filled with a weak electrolyte fluid. Charge buildup at the two poles (electrodes) and the formation of an electric double layer shields the channel, making the effective field in the bulk fluid very weak. Recent computational research suggests that pulsed field protocols, however, should improve retention and may enhance separation in EFFF through systematic disruptions of the double layer resulting in a stronger effective field in the bulk fluid. Improved retention has already been demonstrated experimentally. Accurate modeling and subsequent device optimization and design, however, depends, in part, on formulating a suitable model for the capacitative response of the channel and double layer at the electrode surfaces. Early models do not correctly describe experimentally observed current-time response and are not physically meaningful even when accurate mathematical fits of the data are realized. A new model and conceptual framework based on electrical resistance and capacitance variations of the double layer is suggested here. Physical interpretations of the electrical response have been developed and compared to published experimental data sets.

Electrochemistry↗

Impedance profiles of peripheral and central neurons.

The electrical impedance of trigeminal ganglion cells (in vivo) and hippocampal CA1 neurons (in vitro) of guinea pigs was measured in the frequency range of 5-1250 Hz using intracellular recording techniques with single microelectrodes and computerized methodology. The transfer functions of the electrode and the electrode-neuron system were computed from the ratio of fast Fourier transforms of the output voltage response from the neuron and input current composed of sine waves with rapidly increasing frequency which displaced membrane potential by 2-5 mV. We believe these to be the first measurements of complex impedance and transfer functions in peripheral and central neurons of vertebrates and the first use of such input current functions. The majority of trigeminal ganglion cells did not exhibit electrical behaviour ascribable to a simple resistance-capacitance (RC) circuit but showed a hump at low frequencies (5-250 Hz) in the computed transfer function, probably attributable to resonance. The transfer function in less than 20% of the trigeminal neurons could be fitted approximately to a theoretical transfer function (resistance in series with a parallel RC circuit model) providing values for electrode resistance, effective input resistance, and effective input capacitance. The transfer functions measured in hippocampal CA1 neurons were characterized by a rapid fall-off in the low frequency range (less than 200 Hz). Impedance locus plots approximate the locus corresponding to a series RC circuit in parallel with a parallel RC circuit.

Animals↗

On the mechanism of electrical coupling between cells of early Xenopus embryos.

The mechanism of electrical coupling between cells of early Xenopus embryos has been studied by examination of the nonjunctional membrane resistances and capacitances as a function of cleavage stage, the junctional and nonjunctional membrane resistances as functions of time during the first cleavage, and the electrical properties of the primitive blastocoel. The changes in membrane resistances and capacitances during the first two cleavages may be completely explained by the addition of new membrane, identical in specific resistance and capacitance to the original membrane, at a constant rate to furrows which are electrically connected to the perivitelline space. Microelectrode recording from the primitive blastocoel indicates that there is no electrical difference detectable between it and the perivitelline space. These results are discussed in the context of current theories of the mechanism of intercellular electrotonic coupling.

Animals↗

Hydraulic analogs as teaching tools for bioelectric potentials.

Hydraulic analogs of bioelectrical potentials are proposed as teaching tools in helping students with no formal background in physics and mathematics. Membrane capacitance is simulated by a water reservoir, V, whose variable level is the membrane potential. Resting membrane potential is simulated by a large capacitance reservoir of fixed level, connected to reservoir V through a tube having the role of the electrical conductance of the membrane. Injection of electrical current into the cell is simulated by injection of water into the membrane capacitance reservoir. Reversal potentials of the end-plate potential are simulated by another water reservoir, with fixed level (analogous to the reversal potential of the end-plate potential) connected to the membrane capacitance reservoir through a tube corresponding to the acetylcholine-activated ion channels. Different phases of the synaptic potential are then described using the hydraulic analogs. Hydraulic analogs have proved, in our experience, to be an efficient tool in complementing the already established electrical equivalents.

Education, Medical↗

Alamethicin adsorption to a planar lipid bilayer.

The effect of alamethicin and its derivatives on the voltage-dependent capacitance of phosphatidylethanolamine (squalane) membranes was measured using two different methods: lock-in detection and voltage pulse. Alamethicin and its derivatives modulate the voltage-dependent capacitance at voltages lower than the voltage at which alamethicin-induced conductance is detected. The magnitude and sign of this alamethicin-induced capacitance change depends on the aqueous alamethicin concentration and the kind of alamethicin used. Our experimental data can be interpreted as a potential-dependent pseudocapacitance associated with adsorbed alamethicin. Pseudocapacitance is expressed as a function of alamethicin charge, its concentration in the bathing solution and the applied electric field. The theory describes the dependence of the capacitance on applied voltage and alamethicin concentration. When alamethicin is neutral the theory predicts no change of the voltage-dependent capacitance with either sign of applied voltage. Experimental data are consistent with the model in which alamethicin molecules interact with each other while being adsorbed to the membrane surface. The energy of this interaction depends on the alamethicin concentration.

Alamethicin↗

PSpice modeling of capacitive microfabricated ultrasonic transducers.

Capacitive microfabricated ultrasonic transducers (cMUTs) are the newest and potentially the most promising devices to convert electrical into acoustic signals and vice-versa. These devices are based on the capacitance modulation of a microcondenser which is obtained by microfabrication onto a silicon substrate. The aim of this paper is to describe a PSpice model of the cMUT, based on an analytical distributed model previously reported (IEEE Trans. UFFC 49 (2) (2002) 159-168), which can be used to simulate the performances of a general ultrasound system, either in frequency or time domain. The PSpice model consists of a capacitor with a parallel resistor, which represent the static capacitance and the loss and bias resistances of the transducer, respectively, plus two quadrupoles (GLAPLACE) modeling the mechanical impedance of the membranes and the radiation impedance of the medium. The usefulness of a PSpice model is the possibility to simulate and optimize the cMUT transducers in transmission and reception, along with driving and receiving electronics, in a general ultrasound system. Experimental measurements on a 5 MHz cMUT operating in pulse-echo are in good agreement with model predictions.

Journal Article↗

Interfacing a silicon chip to pairs of snail neurons connected by electrical synapses.

Future hybrid neuron-semiconductor chips will consist of complex neural networks that are directly interfaced to electronic integrated circuits. They will help us to understand the dynamics of neuronal networks and may lead to novel computational facilities. Here we report on an elementary step towards such neurochips. We designed and fabricated a silicon chip for multiple two-way interfacing, and cultured on it pairs of neurons from the pedal ganglia of the snail Lymnaea stagnalis. These neurons were joined to each other by an electrical synapse, and to the chip by a capacitive stimulator and a recording transistor. We obtained a set of neuroelectronic units with sequential and parallel signal transmission through the neuron-silicon interface and the synapse, with a bidirectionally interfaced neuron-pair and with a signal path from the chip through a synaptically connected neuron pair back to the chip. The prospects for assembling more involved hybrid networks on the basis of these neuroelectronic units are considered.

Animals↗

Fenamates: a novel class of reversible gap junction blockers.

The effect of fenamates on gap junctional intercellular communication was investigated in monolayers of normal rat kidney (NRK) fibroblasts and of SKHep1 cells overexpressing the gap junction protein connexin43 (Cx43). Using two different methods to study gap junctional intercellular communication, single electrode voltage-clamp step response measurements and dye microinjection, we show that fenamates are reversible blockers of Cx43-mediated intercellular communication. After adding fenamates to a confluent monolayer of electrically coupled NRK fibroblasts, the voltage step-induced capacitive current transient changed from a transient characteristic for charging multiple coupled cell capacitances to one characteristic for a single cell in isolation. The capacitance of completely uncoupled cells was 19.7 +/- 1.0 pF (mean +/- S.E.M.; n = 11). Junctional conductance between the patched cell and the surrounding cells in the monolayer changed from >140.7 +/- 9.6 nS (mean +/- S.E.M.; n = 14) to <1.4 +/- 0.4 nS (mean +/- S.E.M.; n = 11) after uncoupling. Electrical coupling could be restored to >51.8 +/- 4.2 nS (mean +/- S.E.M.; n = 11) by washout of the fenamates. Voltage-clamp step response measurements showed that the potency of fenamates in inhibiting electrical coupling decreases in the order meclofenamic acid > niflumic acid > flufenamic acid. The half-maximal concentration determined by dye-coupling experiments was 25 and 40 microM for meclofenamic acid and flufenamic acid, respectively. Inhibition of gap junctional communication by fenamates did not involve changes in intracellular calcium or pH, and was unrelated to protein kinase C activity or an inhibition of cyclooxygenase activity. Voltage-clamp step response measurements in confluent monolayers of SKHep1 cells that had been stably transfected with Cx43 revealed that fenamates are potent blockers of Cx43-mediated intercellular communication. In conclusion, fenamates represent a novel class of reversible gap junction blockers that can be used to study the role of Cx43-mediated gap junctional intercellular communication in biological processes.

Cell Communication↗

Variational formulation of open-ended coaxial line in contact with layered biological medium.

An open-ended coaxial probe designed to measure layered biological media is analyzed with a new method. The probe is considered as an electrostatic circuit element whose capacitance is solved using a stationary functional. The fundamental transverse electric and magnetic field (TEM)-mode and the series of evanescent wavemodes in the coaxial cable are used as basis functions. The field outside the probe is solved using a Hankel transform. The capacitance is calculated for homogeneous materials and two-layer structures and the results are compared with values measured with a phantom model. The method can be easily extended for structures with an arbitrary number of layers. A practical approximation for two-layer cases, originally developed to take into account the effect of subcutaneous fat in skin measurements, is presented and its validity for different combinations of dielectric constants and the thickness of the first layer is demonstrated. The static approximation limits the frequency range, but it covers biological measurements up to 500 MHz. The developed method is accurate and easy to adopt in practice.

Adipose Tissue↗

Comments on the use of electromagnetic fields in biological studies.

For biological or cellular experiments using electromagnetic fields it is essential that the parameters defining the field be accurately specified if the results are to be meaningful and are to be compared with the same experiment conducted in a different laboratory. The interaction of living systems with electric and magnetic fields can come only through forces exerted on the charges on the system. If the charges are stationary the only origin of the force is the electric field. The electric field may be established by charge distributions, as in "capacitative plate" experiments, or by time-varying magnetic fields consists of a pair of coaxial coils each of equal radius and separated by a distance about equal to the radius. The electric field induced by a varying current in such a pair of coils varies both in space and in time. The field is always zero on the axis of symmetry, and increases to a maximum near the radius of the coils. The strength is proportional to the time-rat-of-change of the current in the coil, which depends not only on the amplitude and shape of the voltage pulse applied to the coil but also on the resistance and inductance of the coil. The purpose of this note is to describe how the important physical parameters may be determined.

Biological Transport↗

Capacitance of the surface and transverse tubular membrane of frog sartorius muscle fibers.

The passive electrical properties of glycerol-treated muscle fibers, which have virtually no transverse tubules, were determined. Current was passed through one intracellular microelectrode and the time course and spatial distribution of the resulting potential displacement measured with another. The results were analyzed by using conventional cable equations. The membrane resistance of fibers without tubules was 3759 +/- 331 ohm-cm(2) and the internal resistivity 192 ohm-cm. Both these figures are essentially the same as those found in normal muscle fibers. The capacitance of the fibers without tubules is strikingly smaller than normal, being 2.24 +/- 0.14 microF/cm(2). Measurements were also made of the passive electrical properties of fibers in a Ringer solution containing 400 mM glycerol (which is used in the preparation of glycerol-treated fibers). The membrane resistance and capacitance are essentially normal, but the internal resistivity is somewhat reduced. These results show that glycerol in this concentration does not directly affect the membrane capacitance. Thus, the figure for the capacitance of glycerol-treated fibers, which agrees well with previous estimates made by different techniques, represents the capacitance of the outer membrane of the fiber. Estimates of the capacitance per unit area of the tubular membrane are made and the significance of the difference between the figures for the capacitance of the surface and tubular membrane is discussed.

Action Potentials↗

Membrane resistivity estimated for the Purkinje neuron by means of a passive computer model.

A multicompartment passive electrotonic computer model is constructed for the cerebellar Purkinje cell of the guinea-pig. The model has 1089 coupled compartments to accurately represent the morphology of the Purkinje cell. In order that the calculated behavior of the model fit the published electrophysiological observations of somatic and dendritic input conductance, the neural membrane resistivity must be spatially non-uniform. The passive electrical parameter values for which the model best fits the observations of input conductances, pulse attenuation and current-clamp voltage transients are rm,dend = 45,740 omega cm2, rm,soma = 760 omega cm2, ri = 225 omega cm and cm = 1.16 microF/cm2 (the membrane and cytoplasm specific resistivities and membrane specific capacitance, respectively). The model with these parameter values is electrically compact, with electrotonic length X = 0.33 and dendritic dominance ratio p = 0.44. Analysis of the calculated voltage transient of the multicompartment model by the methods of equivalent-cylinder cable theory is shown to result in very different and unreliable conclusions. The significance for neuronal function of the estimated electrical parameter values is discussed. The possible effect of active conductances on these conclusions is assessed.

Animals↗

Assessment of the performance characteristics of a prototype 12-element capacitive contact flexible microstrip applicator (CFMA-12) for superficial hyperthermia.

The electrical performance of the CFMA-12 operating at 433 MHz is assessed under laboratory conditions using a RF network analyser. From measurements of the scattering parameters of the CFMA-12 on both a multi-layered muscle- and fat/muscle-equivalent phantom, the optimal water bolus thickness, at which the transfer of the energy to the phantom configuration is maximal, is determined to be approximately 1 cm. The SAR distribution of the CFMA-12 in a multi-layered muscle-equivalent phantom is characterized using Schottky diode sheets and a TVS-600 IR camera. From the SAR measurements using the Schottky diode sheets it is shown that the contribution of the E(x) component to the SAR (SAR(x)) is maximal 7% of the contribution of the E(y)component to the SAR (SAR(y)) at different layers in both phantom configurations. The complete SAR distribution (SAR(tot)) at different depths is measured using the power pulse technique. From these measurements, it can be seen that SAR(y)at a depth of 0 cm in the muscle-equivalent phantom represents up to 80% of SAR(tot). At 1 and 2 cm depth, SAR(y) is up to 95% of SAR(tot). Therefore, in homogeneous muscle-equivalent phantoms, E(y) is the largest E-field component and measurement of SAR(y) distribution is sufficient to characterize SAR-steering performance of the CFMA-12. SAR steering measurements at 1 cm depth in the muscle-equivalent phantom show that the SAR maximum varies by 40% (1 SD) around the average value of 38.8 W kg(-1) (range 10-65 W kg(-1)) between single antenna elements. The effective fieldsize (E(50)) varies by 14% (1 SD) around the average value of 19.1 cm(2).

Absorption↗

Hemodynamic mechanisms in CPR: a theoretical rationale for resuscitative thoracotomy in non-traumatic cardiac arrest.

Experimental work over the past decade has revealed three distinct mechanisms for generating artificial circulation during cardiac arrest and resuscitation. To isolate these mechanisms and study them in pure form, and in particular to characterize circulation during open vs. closed chest cardiopulmonary resuscitation (CPR), we developed an electrical model of the human circulatory system. Heart and blood vessels were modeled as resistive-capacitive networks, pressures in the chest, abdomen, and vascular compartments as voltages, blood flow as electric current, blood inertia as inductance, and the cardiac and venous valves as diodes. External pressurization of thoracic and abdominal vessels, as would occur in CPR, was simulated by application of half-sinusoidal voltage pulses. Simulations included two modes of creating artificial circulation: the cardiac pump mechanism, in which the atria and ventricles of the model were pressurized simultaneously, as occurs during open chest cardiac massage, and the thoracic pump mechanism, in which all intrathoracic elements of the model were pressurized simultaneously, as is likely to occur in closed chest CPR. The two mechanisms were compared for the same peak applied pressure (80 mmHg). Pure cardiac pump CPR generated near normal systemic perfusion pressures throughout the compression cycle. Pure thoracic pump CPR generated much lower systemic perfusion pressure only during the diastolic phase of the compression cycle. Simulation of cardiac compression at rates from 40 to 100/min produced total flows of 2500-3300, myocardial flows of 150-250 and cranial flows of 600-800 ml/min, depending on the compression rate. In contrast, thoracic pump CPR produced a total flow of approx. 1200, myocardial flow of 70, and cranial flow of 450 ml/min, independently of the compression rate. Direct cardiac compression is an inherently superior hemodynamic mechanism, because it can generate greater perfusion pressure throughout the compression cycle. If one presumes that improved blood flow during CPR is the key to more successful resuscitation, then it is reasonable to conclude that direct heart massage is the most effective available way to achieve this end.

Computer Simulation↗

Cardiac, thoracic, and abdominal pump mechanisms in cardiopulmonary resuscitation: studies in an electrical model of the circulation.

To investigate alternative mechanisms generating artificial circulation during cardiopulmonary resuscitation (CPR), an electrical model of the circulation was developed. Heart and blood vessels were modeled as resistive-capacitive networks; pressures in the chest, abdomen, and vascular compartments as voltages; blood flow as electric current; blood inertia as inductance; and the cardiac and venous valves as diodes. External pressurization of thoracic and abdominal vessels, as would occur in CPR, was simulated by application of half-sinusoidal voltage pulses. Three modes of creating artificial circulation were studied: cardiac pump (CP), in which the atria and ventricles of the model were pressurized simultaneously; thoracic pump (TP), in which all intrathoracic elements of the model were pressurized simultaneously; and abdominal pump (AP), in which the abdominal aorta and inferior vena cava of the model were pressurized simultaneously. Flow was greatest with the CP, less with the TP, and least with the AP mechanism. However, the AP could be practically combined with either the CP or TP by interposition of abdominal compressions between chest compressions (IAC-CPR). Our model predicts that this combined method can substantially improve artificial circulation, especially when cardiac compression does not occur and chest compression invokes only the thoracic pump mechanism.

Abdomen↗