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PubMed2000

Role of virtual electrodes in arrhythmogenesis: pinwheel experiment revisited.

INTRODUCTION: Recent experimental evidence demonstrates that a point stimulus generates a nonuniform distribution of transmembrane potential (virtual electrode pattern) consisting of large adjacent areas of depolarization and hyperpolarization. This simulation study focuses on the role of virtual electrodes in reentry induction. METHODS AND RESULTS: We simulated the electrical behavior of a sheet of myocardium using a two-dimensional bidomain model with straight fibers. Membrane kinetics were represented by the Beeler-Reuter Drouhard-Roberge model. Simulations were conducted for equal and unequal anisotropy ratios. S1 wavefront was planar and propagated parallel or perpendicular to the fibers. S2 unipolar stimulus was cathodal or anodal. With regard to unequal anisotropy, for both cathodal and anodal stimuli, the S2 stimulus negatively polarizes some portion of membrane, deexciting it and opening an excitable pathway in a region of otherwise unexcitable tissue. Reentry is generated by break excitation of this tissue and subsequent propagation through deexcited and recovered areas of myocardium. Figure-of-eight and quatrefoil reentry are observed, with figure-of-eight most common. Figure-of-eight rotation is seen in the direction predicted by the critical point hypothesis. With regard to equal anisotropy, reentry was observed for cathodal stimuli only at strengths > -95 A/m. CONCLUSION: The key to reentry induction is the close proximity of S2-induced excited and deexcited areas, with adjacent nonexcited areas available for propagation.

Anisotropy↗
PubMed1992

Effects of steady electric fields on human retinal pigment epithelial cell orientation and migration in culture.

Low-level, steady electric fields of 6-10 volts/cm stimulated directional orientation and translocation of cultured human retinal pigment epithelial cells. The orientative movements (galvanotropism) consisted of somatic elongation of the cells into spindle shapes, followed by pivotal alignment orthogonal to the field. The anodal edges of the cells underwent retraction of their plasmalemmal extensions, while the cathode edges and the longitudinal ends developed lamellipodia and ruffled membranes. These tropic movements were followed by a translocational movement (galvanotaxis) of the cells towards the cathode. Staining of these migrating cells for actin showed the accumulation of stress fibers at the leading (cathodal) edge, as well as at the longitudinal ends of the elongated somata. These results suggest that endogenous, biologically-generated electric fields (eg., injury currents) may play a role in the guidance and migration of retinal pigment epithelial cells after retinal injury.

Actins↗
PubMed1986

Dynamic aspects of amphibian neurite growth and the effects of an applied electric field.

The dynamics of growth of earliest spinal neurites from Xenopus laevis have been studied in vitro in the presence and absence of an applied d.c. electric field. Control and cathode-directed neurites grew at a rate of about 30 micron/h: growth of anodal-facing neurites was 8 times slower. Periods of arrested growth were common in cultured neurones; these lasted 2-3 times longer in an applied electric field. The likelihood and the severity of neurite reabsorption was greatest in neurites directed towards the anode. Many neurites turned to direct their growth towards the cathode. As this happened their rate of growth increased 2-3-fold. The electric field further shaped neurite morphology by increasing the number of filopodia at the growth cone and by increasing the number of cytoplasmic spines along a neurite shaft. The electric field induced an asymmetry in the distribution of these cytoplasmic projections; greater numbers being found on the cathodal-facing than on the anodal-facing side. Implications of these data for nerve growth in development and in regeneration are discussed.

Animals↗
PubMed1988

Receptors in the bill of the platypus.

1. Afferent responses were recorded from filaments of the trigeminal nerve in each of two platypuses (Ornithorhynchus anatinus) anaesthetized with alpha-chloralose. All receptive fields were located along the lateral border of the upper bill. Discrete receptive fields could be identified as belonging to two distinct classes of sensory receptor. 2. The most prominent response was an irregular resting discharge which could be increased or decreased by weak electric pulses. These receptors were insensitive to moderately strong mechanical stimulation, and it was concluded that they were electroreceptors. 3. Each electroreceptor had a single spot of maximum sensitivity on the bill surface. When the stimulating electrode over this spot was the cathode it excited the receptor for the duration of the stimulating pulse, using stimulus strengths as low as 20 mV. When it was the anode, it inhibited the discharge. Cathodal excitation was followed by rebound inhibition and anodal inhibition by rebound excitation. 4. Receptors responded to cathodal steps with an initial high-frequency burst of impulses, followed by a lower maintained rate of discharge. Rapidly changing pulses were similarly effective in exciting receptors, adding support to the claim that platypuses are able to detect moving prey by the electrical activity associated with muscle contraction. 5. The centres of the receptive fields of two electroreceptors were marked by the insertion of fine entomological pins. Histological examination established the presence of a large mucus-secreting gland at the marked spot. The epidermal duct of the gland contained an elaborate myelinated innervation, with morphologically distinct axon terminals that we identify as the electroreceptors. 6. As well as electroreceptors, the skin of the bill contained three kinds of mechanoreceptors: slow-adapting receptors, rapidly adapting, vibration-sensitive receptors and receptors with an intermediate adaptation rate. The slowly adapting receptors were characterized by their low threshold to mechanical stimuli, irregular discharge and significant dynamic sensitivity. Vibration receptors showed maintained responses to sinusoidal vibration of the skin up to 600 Hz. 7. These experiments confirm an earlier report that the platypus bill is an electrodetector organ. The presence of electroreceptors of a unique structure and supplied by the trigeminal nerve indicates that electroreception has evolved independently in monotremes. This in turn emphasizes that monotremes are a highly evolved group which split off from the main mammalian stem a long time ago.

Action Potentials↗
PubMed2003

Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

Adult↗
PubMed2000

Selective microstimulation of central nervous system neurons.

The goal of this study was to identify stimulus parameters and electrode geometries that were effective in selectively stimulating targeted neuronal populations within the central nervous system (CNS). Cable models of neurons that included an axon, initial segment, soma, and branching dendritic tree, with geometries and membrane dynamics derived from mammalian motoneurons, were used to study excitation with extracellular electrodes. The models reproduced a wide range of experimentally documented excitation patterns including current-distance and strength-duration relationships. Evaluation of different stimulus paradigms was performed using populations of fifty cells and fifty fibers of passage randomly positioned about an extracellular electrode(s). Monophasic cathodic or anodic stimuli enabled selective stimulation of fibers over cells or cells over fibers, respectively. However, when a symmetrical charge-balancing stimulus phase was incorporated, selectivity was greatly diminished. An anodic first, cathodic second asymmetrical biphasic stimulus enabled selective stimulation of fibers, while a cathodic first, anodic second asymmetrical biphasic stimulus enabled selective stimulation of cells. These novel waveforms provided enhanced selectivity while preserving charge balancing as is required to minimize the risk of electrode corrosion and tissue injury. Furthermore, the models developed in this study can predict the effectiveness of electrode geometries and stimulus parameters for selective activation of specific neuronal populations, and in turn represent useful tools for the design of electrodes and stimulus waveforms for use in CNS neural prosthetic devices.

Animals↗
PubMed2000

Chondrocyte translocation response to direct current electric fields.

Using a custom galvanotaxis chamber and time-lapse digital video microscopy, we report the novel observation that cultured chondrocytes exhibit cathodal migration when subjected to applied direct current (DC) electric fields as low as 0.8 V/cm. The response was dose-dependent for field strengths greater than 4 V/cm. Cell migration appeared to be an active process with extension of cytoplasmic processes in the direction of movement. In some cells, field application for greater than an hour induced elongation of initially round cells accompanied by perpendicular alignment of the long axis with respect to the applied field. Antagonists of the inositol phospholipid pathway, U-73122 and neomycin, were able to inhibit cathodal migration. Cell migration toward the cathode did not require the presence of serum during field application. However, the directed velocity was nearly threefold greater in studies performed with serum. Studies performed at physiologic temperatures (approximately 37 degrees C) revealed a twofold enhancement in migration speed compared to similar studies at room temperature (approximately 25 degrees C). Findings from the present study may help to elucidate basic mechanisms that mediate chondrocyte migration and substrate attachment. Since chondrocyte migration has been implicated in cartilage healing, the ability to direct chondrocyte movement has the potential to impact strategies for addressing cartilage healing/repair and for development of cartilage substitutes.

Animals↗
PubMed1962

Dialyzable cofactor in nerve growth promoting protein from mouse salivary glands.

Cohen's method for preparing the nerve growth factor from mouse submaxillary glands was followed to the last ammonium sulfate fraction. Further purification was accomplished with carboxymethyl- and diethylaminoethyl- column chromatography. Three peaks were obtained for each column; the third peak obtained with diethylaminoethyl cellulose was the most active. Electrophoresis of this active fraction produced one anodal and two cathodal bands. Each band was inactive for nerve outgrowth. However combinations of the cathodal bands produced 3+ growth. One cathodal band was not dialyzable; the other was dialyzable and negative for ultraviolet absorption at 280 millimicrons.

Animals↗
PubMed1979

Behavior of Escherichia coli K antigens K88ab, K88ac, and K88ad in immunoelectrophoresis, double diffusion, and hemagglutination.

Porcine enteropathogenic Escherichia coli strains were found to possess a variant of the K88 antigen provisionally termed K88ad. We propose to include this antigen into the international E. coli typing scheme. Ultrasonic extracts of field strains of E. coli possessing the K88ab, K88ac, or K88ad antigen and their E. coli K-12 K88+ transconjugants showed a specific K88 precipitation line in immunoelectrophoresis and double diffusion only when grown at 37 degrees C, but not when grown at 18 degrees C. By using agarose gels, K88ab, K88ac, and K88ad antigens showed anodic mobility in immunoelectrophoresis. When using Difco Noble agar gels, K88ad was not mobile or anodic, K88ab was cathodic; K88ac of 17 strains was cathodic and of 24 strains was anodic. The immunoelectrophoretic behavior of a K88 antigen (K88ab, K88ac, or K88ad) did not alter after transfer of the corresponding plasmid to E. coli K-12. Anodic and cathodic K88ac antigens could not be distinguished serologically. The differences between the results obtained in Noble agar gels and agarose gels are due to electro-endosmotic flow. We describe a procedure which increases the detection level of K88+ transconjugants in a mating mixture. It is based on the specific mannose-resistant attachment of K88+ cells to guinea pig erythrocytes.

Animals↗
PubMed1982

Immunochemical analysis of streptococcal group A, B, and C carbohydrates, with emphasis on group A.

Streptococcal group A, B, and C carbohydrates were analyzed by counterimmunoelectrophoresis, immunoelectrophoresis, and inhibition of immunoprecipitation. Extracts of streptococci group A or C were shown by counterimmunoelectrophoresis to contain both anodic and cathodic migrating components. In immunoelectrophoresis, group A and C substances formed a continuous precipitation line stretching from the anode to the cathode, suggesting a heterogeneous population of molecules with immunochemical identity. This identity was confirmed by inhibition of immunoprecipitation, in which both anodic and cathodic immunoprecipitates were inhibited by the same constituent sugars: group A-anti-A was inhibited by N-acetylglucosamine, and group C-anti-C was inhibited by N-acetylgalactosamine. Extracts of group B showed only anodic migration in counterimmunoelectrophoresis and a narrow, anodic arc in immunoelectrophoresis. The group B-anti-B reaction was inhibited by rhamnose. Carbohydrates of variant strains of group A streptococci were also analyzed by the same methods. The results suggest that the heterogeneity of group A carbohydrate may have resulted from attachment of various amounts of N-acetylglucosamine to the polyrhamnose backbone.

Acetylgalactosamine↗
PubMed1985

Antigenic heterogeneity of an alkali-soluble, water-soluble cell wall extract of Coccidioides immitis.

The antigenic composition of an alkali-soluble, water-soluble cell wall extract of Coccidioides immitis, designated C-ASWS, was assessed by two-dimensional immunoelectrophoresis against goat antisera to C-ASWS and coccidioidin. The results established that C-ASWS from mycelia or spherule cell walls is heterogeneous in composition, containing two distinct antigenic components. One is present as a polymer that is antigenically identical to a polymeric antigen in coccidioidin, designated antigen 2. The other component detected in C-ASWS presented an unusual precipitin pattern in that a cathodal leg was demonstrable in the absence of an anodal leg. This incomplete precipitinogen was also detected in coccidioidin. In addition to the finding that C-ASWS is antigenically heterogeneous, the results provide evidence that the conformational and/or configurational structure of the C-ASWS antigen 2 (or antigen 2-like polymer) is altered during physicochemical extraction. This conclusion is based upon the finding that the immunoelectrophoretic profile of the C-ASWS polymer differs from that of coccidioidin antigen 2. The C-ASWS polymer is characterized by having a small cathodal precipitin peak connected to a large anodal peak, whereas coccidioidin antigen 2 is characterized by a predominant cathodal peak.

Antigens, Fungal↗
PubMed1987

Adhesion of Aeromonas salmonicida strains associated with net electrostatic charges of host tissue cells.

The adhesion of Aeromonas salmonicida, the pathogenic bacterium of fish furunculosis in salmon and trout, to the surface of host tissue cells was investigated with two fish tissue culture cell lines (RTG-2 cells from rainbow trout, Salmo gairdneri, and CHSE-214 cells from chinook salmon, Oncorhynchus tshawytscha) and four A. salmonicida strains. Bacterial cells of pathogenic strains were highly adhesive to RTG-2 and CHSE-214 cells and were negatively charged in the net electrostatic charges, as determined by electrophoresis on filter paper strips at pH 7, whereas bacterial cells of nonpathogenic strains were nonadhesive and positively charged. The electrophoresis of RTG-2 and CHSE-214 cells with balanced salt solution (BSS), phosphate-buffered saline, or fish serum diluted with BSS (pH 7) was carried out with an appropriate electrophoretic apparatus that was devised for this study. After electrophoresis with 20 mA of direct current for 15 min at pH 7, the electrophoretic dispositions of these tissue culture cells were determined by the mode of frequency of occurrence of these cells in the partitioned chambers of the device. RTG-2 and CHSE-214 cells with BSS and fish serum were attracted from the central chamber (to which each cell sample was added) to the cathode chambers, but no attraction was detected when these cells were used with phosphate-buffered saline. Noradrenaline- and phosphoenolpyruvate-pretreated RTG-2 cells migrated more to the cathode chambers, whereas succinate- and valine-pretreated RTG-2 cells moved to the anode chambers. These movements to the cathode and anode were alleviated by the use of RTG-2 cells preincubated with pathogenic and nonpathogenic bacterial cells, respectively. The adhesion of the pathogenic bacteria to RTG-2 cells was enhanced by the use of RTG-2 cells pretreated with noradrenaline and phosphoenolpyruvate, whereas the nonpathogenic bacteria were adherent to RTG-2 cells pretreated with succinate and valine. These findings indicate that the adhesion of A. salmonicida strains to host tissue cells is closely associated with mutually converse net electrostatic charges.

Aeromonas↗
PubMed1994

Electric fields induce curved growth of Enterobacter cloacae, Escherichia coli, and Bacillus subtilis cells: implications for mechanisms of galvanotropism and bacterial growth.

Directional growth in response to electric fields (galvanotropism) is known for eukaryotic cells as diverse as fibroblasts, neurons, algae, and fungal hyphae. The mechanism is not understood, but all proposals invoke actin either directly or indirectly. We applied electric fields to bacteria (which are inherently free of actin) to determine whether actin was essential for galvanotropism. Field-treated (but not control) Enterobacter cloacae and Escherichia coli cells curved rapidly toward the anode. The response was both field strength and pH dependent. The direction of curvature was reversed upon reversal of field polarity. The directional growth was not due to passive bending of the cells or to field-induced gradients of tropic substances in the medium. Field-treated Bacillus subtilis cells also curved, but the threshold was much higher than for E. cloacae or E. coli. Since the curved morphology must reflect spatial differences in the rates of cell wall synthesis and degradation, we looked for regions of active wall growth. Experiments in which the cells were decorated with latex beads revealed that the anode-facing ends of cells grew faster than the cathode-facing ends of the same cells. Inhibitors of cell wall synthesis caused spheroplasts to form on the convex regions of field-treated cells, suggesting that the initial curvature resulted from enhanced growth of cathode-facing regions. Our results indicate that an electric field modulates wall growth spatially and that the mechanism may involve differential stimulation of wall growth in both anode- and cathode-facing regions. Electric fields may therefore serve as valuable tools for studies of bacterial wall growth. Use of specific E. coli mutants may allow dissection of the galvanotropic mechanism at the molecular level.

Bacillus subtilis↗
PubMed1992

Radiographic detail and variation of the nominal focal spot size: the "focal effect".

It is not generally appreciated that there is a gradation of the focal spot size from the anode to cathode end of an x-ray field that can dramatically affect radiographic detail from one end of a radiograph to the other. The authors name this gradation the "focal effect." Gradations in radiation intensity and focal spot size were measured from anode end to cathode end of a 14 x 17-inch field and were visually demonstrated with lymphangiograms and line-pair patterns. The degradation in spatial resolution along the anode-cathode axis was found to be as much as 75%, depending on the orientation of the patient with respect to the x-ray tube. Radiographic detail is, therefore, significantly improved (even when the large focal spot is used) by exploiting the focal effect and placing the body part requiring the best radiographic detail at the anode end of the table.

Contrast Media↗
PubMed1992

Ventricular fibrillation is not an anodally induced phenomenon in open-chest dogs.

It is generally assumed that ventricular fibrillation evoked by electrical stimulation depends on anodal excitation. To test this hypothesis, six open-chest dogs were studied with computerized mapping techniques. A plaque electrode array containing 56 closely (2.5-5 mm) spaced bipolar electrodes was placed on the right ventricle. The patterns of activation after premature stimulation and at the onset of multiple responses or ventricular fibrillation were determined when the baseline driving stimuli (S1) were given to the center, and when a 5-ms bipolar single premature stimulus (S2) was given via two electrodes (one anodal and one cathodal) at the opposite edges of the plaque electrode array. The results showed that the classical anodal and cathodal strength-interval curves could be demonstrated by this method. A relatively supernormal period was observed only in the anodal strength-interval curve and coincided with the most vulnerable phase of the cardiac cycle. Although a supernormal period was found only at the anodal site, the origins of excitation at the onset of multiple responses or ventricular fibrillation could be anodal, cathodal, or both. When the S2 polarity was reversed, the origin of multiple responses or ventricular fibrillation stayed at the same site and did not change according to the polarity of the S2. These findings indicate that ventricular fibrillation is not an anodally induced phenomenon. The preexisting electrophysiological state at the site of stimulation determines the initiation and maintenance of multiple responses or ventricular fibrillation.

Animals↗
PubMed1988

Excitatory synaptic actions between pairs of neighboring pyramidal tract cells in the motor cortex.

1. By spike-triggered averaging, we documented recurrent individual excitatory postsynaptic potentials (EPSPs) produced in 33 pyramidal tract (PT) cells (target) by the activity of axon collaterals of neighboring single PT cells (reference) in the motor cortex of the cat. 2. The computer was triggered by the spontaneous activity of reference PT cells or by current pulses applied to reference PT cells through the extracellular recording electrode. 3. The threshold for direct activation of PT cells was less than 0.1 microA with an anodal current pulse and 0.2-0.3 microA with a cathodal current pulse. 4. Application of an anodal current pulse directly activated only a single reference PT cell, the surface membrane of which was presumably touched by and sucked with the extracellular recording electrode. 5. When a cathodal current pulse was used, simultaneous activation of neurons or axons other than the reference PT cell was checked by changing the stimulus parameters along the characteristic strength-duration curve for the reference PT cell and/or by comparing averaged EPSPs obtained by cathodal stimulation with those obtained from spontaneous spikes of the reference PT cell. 6. Recurrent individual EPSPs were produced in fast PT cells by activation of neighboring slow PT cells and also of neighboring fast PT cells. Some recurrent individual EPSPs were also observed in slow PT cells. 7. The mean latencies of recurrent individual EPSPs produced by the spontaneous activity of reference slow and fast PT cells were 1.61 (n = 12) and 1.12 ms (n = 8), respectively. Their amplitudes ranged between 30 and 390 microV (n = 33). The rise time observed in fast PT cells with activation of slow and fast PT cells ranged from 1.6 to 3.6 ms (n = 20) and from 0.8 to 1.9 ms (n = 10), respectively. 8. The average conduction velocity of axon collaterals of slow and fast PT cells was estimated to be as slow as that of unmyelinated fibers in the cat. 9. It is suggested that axon collaterals of slow PT cells synapse onto more distal dendrites of fast PT cells than axon collaterals of fast PT cells.

Action Potentials↗
PubMedDate not supplied

Current-induced vasodilation during water iontophoresis (5 min, 0.10 mA) is delayed from current onset and involves aspirin sensitive mechanisms.

Study of the microcirculation by iontophoresis is potentially confounded by any non-specific effects of current application. Laser Doppler flow (LDF, mean +/- SD; arbitrary units; AU) was recorded on the forearms of healthy volunteers during and 20 min following application of 0.10-mA current for 1, 3 and 5 min, using deionised water as a vehicle. Local heating to 44 degrees C was then applied for 24 min to assess maximal vasodilation. Cathodal current applications resulted in delayed and prolonged vasodilation (peak values: 78 +/- 29, 75 +/- 19, 80 +/- 37 AU) whereas anodal peak LDF was 13 +/- 6, 27 +/- 34 and 72 +/- 40 AU for 1-, 3- and 5-min periods of current applications, respectively. From current onset, inflexion points in the responses to 3- and 5-min anodal current applications occurred at 4.5 and 6.5 min, respectively, and at approximately 1.5 min for all cathodal current applications. For 5-min current applications: a preliminary tourniquet ischaemia neither changed the time course nor the amplitude of the response to current application. In this situation, local anaesthesia abolished the current-induced vasodilation. Chronic capsaicin pretreatment decreased the amplitude of the vasodilation. Pretreatment with 500 mg oral aspirin decreased the cathodal vasodilation and abolished the anodal vasodilation, even in the absence of preliminary ischaemia. We conclude that vasodilation to prolonged application of 0.10-mA continuous monopolar current after transient tourniquet ischaemia cannot be exclusively the result of an axon reflex initiated by current onset. This current-induced vasodilation is at least partly dependent on capsaicin-sensitive afferent fibres and relies on aspirin-sensitive mechanisms at both polarities.

Adult↗
PubMedDate not supplied

Elimination of electrically induced iontophoretic artefacts: implications for non-invasive assessment of peripheral microvascular function.

Iontophoretic assessment of skin microvascular function is complicated by the occurrence of electrically induced hyperaemia, especially at the cathode. Studies were performed to identify means of reducing such effects. Skin vasodilator responses were measured using a laser Doppler imager that controlled iontophoretic current delivery. A novel feature involved monitoring voltage across the iontophoresis chambers. Comparison between responses to vehicle (distilled H(2)O), acetylcholine (ACh) and sodium nitroprusside (SNP) showed electrically induced hyperaemia at the cathode associated with the vehicle, whose time course overlapped with that of the SNP response. Voltage across the chambers containing drugs dissolved in H(2)O was significantly (p = 0.018, n = 7) lower than the voltage profile of H(2)O alone. H(2)O iontophoresis was associated with cathodal hyperaemic responses in most subjects, whereas a 0.5% NaCl vehicle produced lower voltages and eliminated this artefact. Voltage.time integral rather than charge was the prime determinant of electrically induced hyperaemic responses. No significant correlation was found between skin fold thickness and either calculated skin resistance (r(2) = 0.0002) or vascular response to ACh (r(2) = 0.13). Smaller chamber size led to higher voltages and greater electrically induced hyperaemic responses. These appear to be prostaglandin dependent as they were ablated by cyclooxygenase inhibition. Use of a low-resistance vehicle combined with larger chamber sizes and lower currents can prevent such artefacts, thereby increasing the robustness of this methodology for clinical assessment of endothelial function.

Acetylcholine↗