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A prospective randomized comparison in humans of biphasic waveform 60-microF and 120-microF capacitance pulses using a unipolar defibrillation system.

BACKGROUND: Improving unipolar implantable cardioverter-defibrillator (ICD) effectiveness has favorable implications for ICD safety, efficacy, and size. Advances in defibrillation efficacy would accelerate ICD ease of use by decreasing device size and by minimizing morbidity and mortality related to an improved defibrillation safety margin. The specific purpose of the present study was to determine whether unipolar defibrillation efficacy could be improved further in humans by lowering biphasic waveform capacitance. METHODS AND RESULTS: We prospectively and randomly compared the defibrillation efficacy of a 60-microF and a 120-microF capacitance asymmetrical 65% tilt biphasic waveform using a unipolar defibrillation system in 38 consecutive cardiac arrest survivors before implantation of a presently available standard transvenous defibrillation system. The right ventricular defibrillation electrode had a 5-cm coil located on a 10.5F lead and was used as the anode. The system cathode was the electrically active 108-cm2 surface area shell (or "can") of a prototype titanium alloy pulse generator placed in a left infraclavicular pocket. The defibrillation pulse was derived from either a 60-microF or a 120-microF capacitance and was delivered from RV-->CAN. Defibrillation threshold (DFT) stored energy, delivered energy, leading-edge voltage and current, pulse resistance, and pulse width were measured for both capacitances examined. The 60-microF capacitance biphasic pulse resulted in a stored-energy DFT of 8.5 +/- 4.1 J and a delivered-energy DFT of 8.4 +/- 4.0 J. In 34 of 38 patients (89%), the stored-energy DFT was < 15 J. Leading-edge voltage at the DFT was 517 +/- 128 V. Mean pulse impedance for the 60-microF waveform was 60.6 +/- 7.1 omega. The 120-microF capacitance biphasic pulse resulted in a stored-energy DFT of 10.1 +/- 7.4 J and a delivered-energy DFT of 10.0 +/- 7.2 J (P = .13 and .13, respectively). In 28 of 38 patients (74%), the stored-energy DFT was < 15 J (P = .052). Leading-edge voltage at the DFT with the 120-microF capacitance pulse was 386 +/- 142 (P < .00001). Mean pulse impedance for the 120-microF waveform was 60.7 +/- 7.0 omega (P = .80). CONCLUSIONS: The results of the present study suggest that a relatively small capacitance, 60 microF, can be used for unipolar defibrillation systems without compromising defibrillation energy requirements compared with more typical ICD capacitance values, but this will require a higher circuit voltage. The use of lower capacitance also provides a modest increase in the percent of patients who have very low energy defibrillation requirements, an important issue should maximum ICD energy be decreased from the present level of 34 J. Such a move to smaller output devices could allow significant decreases in device size, a necessary feature of making cardioverter-defibrillator implantation comparable to that of standard pacemaker surgery.

Adult↗

Accuracy of an optically isolated tetra-polar impedance measurement system.

Accurate electrical transfer impedance measurement at the high frequencies (> 1 MHz) required to characterise blood and intracellular structures is very difficult, owing to stray capacitances between lead wires. To solve this problem, an optically isolated measurement system has been developed using a phase-locked-loop technique for synchronisation between current injection (drive) and voltage measurement (receive) circuits. The synchronisation error between drive and receive circuits was less than 1 ns. The accuracy and reproducibility of the developed system was examined using a tissue equivalent Cole model consisting of two resistors and one capacitor. The absolute value Z and phase shift theta in impedance of the Cole model was measured at 1.25 MHz by both an LCR meter and the isolated measurement system. The difference between the values measured by the isolated measurement system and those measured by the LCR meter was less than 0.27omega (2.9%) in Z and 0.79 degree in theta. The standard deviation was less than 0.09 omega in Z and 0.60 degree in theta.

Electric Impedance↗

Complex admittance of Na+ conduction in squid axon.

The complex admittance, Y(p), of squid axon was measured (4--1000 Hz) during step voltage clamp to obtain linear data on Na+ conduction. Y(p) is used as a spectroscopic tool to identify Na+ and K+ conduction, which dominate Y(p) at low frequencies and can be separated from each other and from the static capacitance. Na+ conduction is readily distinguishable from K+ conduction in that it produces a steady-state negative conductance. The admittance of the Na+ system can show an anomalous resonance or an antiresonance depending on whether the net shunt conductance is negative or positive. Use of the Na+ negative conductance to neutralize leakage yields a measurement of dielectric capacitance at low frequency. A 90 degrees phase angle suggests that the capacitance is ideal.

Animals↗

Electric membrane properties of human DRG neurons in cell culture and the effect of high K medium.

Cell cultures were prepared from human fetal and newborn dorsal root ganglia (DRG) and maintained in culture medium with normal (4 mM) and elevated (20 mM) potassium (K). Both types of cultures were transferred to 4 mM K, and the electrical membrane properties of the DRG neurons characterized by an extensive investigation of resting membrane potential, specific membrane resistance (Rm) and capacitance, time constant (tau), rheobasic current, and various aspects of the action potential, including overshoot, duration (DT), afterhyperpolarization and absolute refractory period (ARP). No previous quantitative determinations of these membrane properties for human neurons could be found. However, our values were in good agreement with those reported for the DRG neurons of other mammalian species both in vitro and in situ. Significant correlations occurred between membrane properties and the developmental age of each specimen used for culturing. However, the data must be interpreted cautiously due to the limited number of specimens used (4) and the possibility of differential responses of the specimens to the experimental situation. Precultivation in high K medium had profound effects on both passive and active membrane properties: the primary effect being to reduce Rm, and as a result tau, DT, and ARP were also reduced. These observations add further support to the hypothesis that high K in vitro can substitute to some extent for trophic factors normally present in situ.

Cells, Cultured↗

Capacitively coupled microplasma for on-column detection of chromatographically separated inorganic gases by optical emission spectrometry.

Two tubular electrodes placed on a capillary tubing are used to couple an electrical ac field of high voltage (20 kV) but low frequency (20 kHz) and about 8 W power inside for generation of the plasma. The emitted radiation is passed to a spectrometer via an optical fibre butted to the side of the capillary. The excitation temperature of the plasma determined from helium emission lines is about 4000 K. It was found possible to detect oxygen from its emission at 777 and 845 nm, hydrogen at 656 nm and sulfur containing species from emission at 923 nm. The carbon-containing species CH4, CO, and CO2 could be determined from an emission band at 385 nm due to CN. Detection limits in the range between about 1 and 10 ng were obtained using a miniature diode array spectrometer.

Chromatography, Gas↗

Bilateral processing in chemical synapses with electrical 'ephaptic' feedback: a theoretical model.

I have developed a detailed biophysical model of the chemical synapse which hosts voltage-dependent presynaptic ion channels and takes into account the capacitance of synaptic membranes. I find that at synapses with a relatively large cleft resistance (e.g., mossy fiber or giant calyx synapse) the rising postsynaptic current could activate, within the synaptic cleft, electrochemical phenomena that induce rapid widening of the presynaptic action potential (AP). This mechanism could boost fast Ca(2+) entry into the terminal thus increasing the probability of subsequent synaptic releases. The predicted difference in the AP waveforms generated inside and outside the synapse can explain the previously unexplained fast capacitance transient recorded in the postsynaptic cell at the giant calyx synapse. I propose therefore the mechanism of positive ephaptic feedback that acts between the postsynaptic and presynaptic cell contributing to the basal synaptic transmission at large central synapses. This mechanism could also explain the supralinear voltage dependence of EPSCs recorded at hyperpolarizing membrane potentials in low extracellular calcium concentration.

Action Potentials↗

En block C-terminal charge cluster reversals in prestin (SLC26A5): effects on voltage-dependent electromechanical activity.

Prestin, the transmembrane motor protein is a novel protein underlying the motility of the outer hair cells. Nonlinear capacitance (NLC) or gating charge current, which can be observed in both auditory and transfected non-auditory cells, is the electrical signature of prestin's electromechanical activity. To test the functional role of the C-terminus of prestin, several charged residue clusters were reversed en-block by site-directed mutagenesis. They are D/E to K at 516, 518, 522, 524, 527, 528 and 531 (cluster a); R/K to D at 571, 572, 573, 576, 577 and 580 (cluster b); R to D at 571; and E/D to K at 608, 609, 610, 611, 612 and 613 (cluster c). These constructs were transfected into Chinese hamster ovary cells (CHO) and NLC recordings were performed to evaluate the effects of these charge substitutions. All of the mutants showed NLC. Charge cluster a reversal significantly reduced the maximum charge movement (Qmax). All but one mutation (charge cluster c reversal) shifted V(h), indicative of the operating voltage range, in the depolarizing direction. None of the mutations affected unitary charge movement (z). These data suggest that the C-terminus of prestin lies outside the membrane voltage field, and may play an important role in controlling the operating voltage range through control of the protein's conformational energy profile via allosteric means.

Amino Acid Sequence↗

Hydrophobic ions amplify the capacitive currents used to measure exocytotic fusion.

The detection of exocytotic fusion in patch-clamped secretory cells depends on measuring an increase in the cell membrane capacitance as new membrane is added to the plasma membrane. However, in the majority of secretory cells, secretory vesicles are too small (< 200 nm in diameter) to cause a detectable signal. We have found that incubations of normal mouse mast cells with the hydrophobic anion dipicrylamine (DPA), increases cell membrane capacitance by about three times. The large capacitive current induced by DPA was voltage-dependent, having a maximum value at -10 mV. The DPA-induced charge movement could be described by a single barrier model in which the DPA molecules move between two stable states in the bulk lipid matrix of the membrane. More importantly, the DPA treatment produced a sevenfold increase in the size of the capacitance steps observed upon the exocytotic fusion of single secretory granules. A similar amplification of DPA on the secretory vesicle capacitance was observed in a cell with larger (< or = 5 microns in diameter) or with smaller secretory granules (< 250 nm in diameter). Additionally, the increased granule membrane capacitance enlarged the transient capacitive discharge measured upon formation of a fusion pore in normal mast cell granules. Our results indicate that hydrophobic ions provide an important tool for high resolution studies of membrane capacitance.

Animals↗

Which of three voltammetric methods, when applied to a reversible electrode reaction, can best cope with double-layer capacitance and severe uncompensated resistance?

The presence of uncompensated resistance and double-layer capacitance confounds the accurate measurements of the bulk concentration of electroreactant and the reversible half-wave potential from an experimental voltammogram. It is pertinent to ask which simple voltammetric technique-chronopotentiometry, linear-scan voltammetry, or potential-step voltammetry-is best able to confront these difficulties. We have carried out a modeling study in an attempt to answer this question. First, we devised an exact method of simulating each variety of reversible voltammogram, incorporating the effects of resistance and capacitance. Next, we developed an unprejudiced method of analyzing these voltammograms to recover both electrochemical parameters. Then we performed a sensitivity analysis on a very large number of simulated voltammograms by measuring the apparent half-wave potential and concentration when slightly erroneous values of resistance and capacitance were employed in the recovery step. Thereby we hoped to ascertain how uncertainty in the magnitudes of the two interfering electrical elements affects the measured values of the two electrochemical parameters. Basing conclusions on the sizes of the four sensitivity indices, we conclude, surprisingly, that linear-scan voltammetry, not chronopotentiometry, is most often the method of choice.

Journal Article↗

A minimal model of the monophasic defibrillation pulse.

A minimal model of the defibrillation capability of a monophasic capacitive discharge pulse is derived from the Weiss-Lapicque strength duration model. The model suggests that present, empirically derived values of pulse durations and tilts are close to optimum for presently used values of capacitors and electrode resistances. The model suggests that neither the tilt nor fixed duration specification is universally superior to the other for dealing with electrode resistance changes. A tilt specification would appear to best handle resistance decreases while a fixed duration specification would best handle resistance increases. The model was used to study the effect of capacitance changes. It appears that the optimum tilt and pulse duration vary with the capacitance value. The model further suggests that decreasing the capacitance from presently used values may lower defibrillation thresholds.

Animals↗

Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing afterpotential.

1. Electrophysiological techniques are described which allow intracellular recording from peripheral myelinated axons of lizards and frogs for up to several hours. The sciatic and intramuscular axons studied here have resting potentials of -60 to -80 mV and action potentials (evoked by stimulation of the proximal nerve trunk) of 50-90 mV. They show a prominent depolarizing afterpotential (d.a.p.), which is present both in isolated axons and in axons still attached to their peripheral terminals. This d.a.p. has a peak amplitude of 5-20 mV at the resting potential, and decays with a half-time of 20-100 msec.2. The peak amplitude of the d.a.p. is voltage-sensitive, increasing to up to 26 mV with membrane hyperpolarization. The d.a.p. disappears as the axon is depolarized to -60 to -45 mV, and does not appear to reverse with further depolarization.3. The d.a.p. is not reduced when bath Ca is replaced by 2-10 mm divalent Mn or Ni. The d.a.p. is not reversed when axons depleted of Cl (by prolonged exposure to Cl-deficient, SO(4)-enriched solutions) are bathed in Cl-rich solutions. These results suggest that the d.a.p. is not mediated by a conductance change specific for Ca or Cl ions. Partial substitution of tetramethylammonium for bath Na, or addition of 10(-5)m-tetrodotoxin to the normal bathing solution, reduces the amplitude of both the action potential and the d.a.p.4. The amplitude of the d.a.p. is not sensitive to bath [K] over the range 1-7.5 mm, provided that all measurements are made at the same holding potential. This result argues that the d.a.p. is not mediated by accumulation of K outside the active axon.5. Treatments expected to inhibit the Na-K exchange pump (cooling from 25 to 10 degrees C, or 0.15 mm-ouabain) do not enlarge or prolong the d.a.p., although they do abolish a slower hyperpolarizing afterpotential seen following repetitive stimulation.6. The passive voltage response of the axon to small injected pulses of depolarizing or hyperpolarizing current shows a prominent, slowly decaying component with a time course similar to that of the d.a.p. Depolarizing current reduces the input resistance of the axon, and increases the rate of decay of both the passive voltage response and the d.a.p. There is a slight conductance increase during the peak of the d.a.p., but the same conductance increase can be produced by a comparable passive depolarization.7. We conclude that the d.a.p. is due mainly to a passive capacitative current, probably resulting from discharge of the internodal axonal membrane capacitance through a resistive current pathway beneath or through the myelin sheath. We suggest that this slow capacitative discharge becomes evident as soon as most of the nodal ionic channels activated during the action potential have closed. An electrical model of the myelinated axon that incorporates the postulated internodal leakage pathway can account both for the prolonged d.a.p. recorded inside the axon, and for the potential profile recorded extra-axonally in or near the internodal periaxonal space.

Action Potentials↗

Theoretical study of rectangular pulse electrical stimulation (RPES) onskin cells (in vivo) under conforming electrodes.

Our previous in vivo experimental results have shown RPES can enhance skin wound healing by using conforming electrodes. Based on an equation of polarization transmembrane voltage [Cole, K. S. 1972], two equations were derived to describe the peak RPES intensity on skin cells in vivo: (1) U = 1.5 a J/sigma, (2) Jm = 1.5 a (J/sigma) (Cm/tau). Where U: polarization transmembrane voltage. a: radius (R) for spherical cells or semi-length (L) for long fibers parallel to the electrical field. J: external imposed pulse current density under the electrode. sigma: average conductivity of skin tissue. Jm: transmembrane displacement current density. Cm: membrane capacitance per unit area and tau: time constant. Calculations indicated that the sensory fibers (SF) would receive the strongest stimulation compared to other cells in skin since generally LSF > or = 100 R. The sensitivity of SF to the stimulation could enhance skin wound healing as well as protect normal skin cells from harmful electroporation. From these theoretical calculations. We proposed a theoretical range of the pulse current density as: U1 sigma/(1.5 L) < or = J < or = U2 sigma/(1.5 L), where U1 and U2 are the excitation threshold voltage (about 0.01 V) and polarization electroporation voltage (about 0.1 V) for a SF respectively, for RPES to enhance skin wound healing.

Electric Conductivity↗

An equivalent circuit for small atrial trabeculae of frog.

An equivalent electrical circuit has been constructed for small atrial trabecula of frog in a double sucrose gap voltage clamp apparatus. The basic strategy in constructing the circuit was to derive the distribution of membrane capacitance and extracellular resistance from the preparation's response to small voltage displacements near the resting condition, when the membrane conductance is presumably quite low. Then standard Hodgkin-Huxley channels were placed in parallel with the capacitance and the results of voltage clamp experiments were simulated. The results suggest that the membranes of the preparation cannot in fact be clamped near the control voltage nor can the ionic currents be measured directly with reasonable accuracy by axon standards. It may or may not be a realizable goal in the future to define the preparation's electrical behavior well enough to permit the ultimate quantitative description of the membrane's specific ion conductances. The result of this paper suggest that if this goal is achieved using the double sucrose gap voltage clamp, it will be by a detailed quantitative accounting for substantial irreducible errors in voltage control, rather than by experimental achievement of good voltage control.

Animals↗

Monitoring living tissues by electrical impedance spectroscopy.

Solving the experimental difficulties associated with measurement of the electrical impedance of living tissues gives access to valuable tissue compartment parameters which are sensed within seconds using minimally invasive, simple metallic electrodes. Extracellular conductivity and cell membrane capacitance can be followed over time under conditions of metabolic toxicity, perfusion loss and thermal stress in liver, brain cortex, and muscle, respectively. Application of this technique in burns therapy allows an accurate estimation of the severity of thermal injury to skeletal muscle, supporting predictions on tissue survival.

Animals↗

The effect of repetitive stimulation on the passive electrical properties of the presynaptic terminal of the squid giant synapse.

The resting electrical properties of the presynaptic terminal of the squid giant synapse have been determined by using constant current pulses. After short periods of repetitive stimulation, the terminal resistance, time constant and capacitance are found to be increased. These changes are absent in terminals bathed in artificial sea water containing no calcium, and sea water containing 5 mM cobalt. It seems likely that these changes are associated with transmitter release.

Animals↗

Electrical stimulation therapies for spinal fusions: current concepts.

Electrical stimulation therapies have been used for more than 30 years to enhance spinal fusions. Although their positive effects on spinal fusions have been widely reported, the mechanisms of action of the technologies were only recently identified. Three types of technologies are available clinically: direct current, capacitive coupling, and inductive coupling. The latter is the basis of pulsed electromagnetic fields and combined magnetic fields. This review summarizes the current concepts on the mechanisms of action, animal and clinical studies, and cost justification for the use of electrical stimulation for spinal fusions. Scientific studies support the validity of electrical stimulation treatments. The mechanisms of action of each of the three electrical stimulation therapies are different. New data demonstrates that the upregulation of several growth factors may be responsible for the clinical success seen with the use of such technologies.

Animals↗

Frequency domain impedance measurements of erythrocytes. Constant phase angle impedance characteristics and a phase transition.

We report measurements of the electrical impedance of human erythrocytes in the frequency range from 1 Hz to 10 MHz, and for temperatures from 4 to 40 degrees C. In order to achieve high sensitivity in this frequency range, we embedded the cells in the pores of a filter, which constrains the current to pass through the cells in the pores. Based on the geometry of the cells embedded in the filter a circuit model is proposed for the cell-filter saline system. A constant phase angle (CPA) element, i.e., an impedance of the form Z = A/(j omega)alpha, where A is a constant, j = square root of -1, omega is angular frequency, and 0 less than alpha less than 1 has been used to describe the ac response of the interface between the cell surface and the electrolyte solution, i.e., the electrical double layer. The CPA and other elements of the circuit model are determined by a complex nonlinear least squares (CNLS) fit, which simultaneously fits the real and imaginary parts of the experimental data to the circuit model. The specific membrane capacitance is determined to be 0.901 +/- 0.036 microF/cm2, and the specific cytoplasm conductivity to be 0.413 +/- 0.031 S/m at 26 degrees C. The temperature dependence of the cytoplasm conductivity, membrane capacitance, and CPA element has been obtained. The membrane capacitance increases markedly at approximately 37 degrees C, which suggests a phase transition in the cell membrane.

Biophysical Phenomena↗

Venous hemodynamics of the lower extremities in response to electrical stimulation.

OBJECTIVE: To evaluate the calf muscle pump function using an air plethysmograph (APG) applied to the lower leg of subjects during three different tiptoe exercises. DESIGN: A controlled trial design was selected to compare the hemodynamic effects of three exercise conditions on a group of able-bodied, healthy patients. SETTING: Testing was performed in an outpatient clinic at a rehabilitation hospital. SUBJECTS: Patient groups were selected from a convenience sample of 10 healthy volunteers with normal venous capacitance and no reflux, determined through impedance pleythysmography before the study. INTERVENTIONS: Three exercise conditions undertaken by each subject consisted of loaded and unloaded lower leg muscle contractions produced by (1) voluntary contraction (VOL), (2) electrical stimulation of the gastocnemius-soleus and tibialis anterior muscles (ES), and (3) combined ES and VOL (ES/VOL). MAIN OUTCOME MEASURE: Hemodynamic measurements of venous filling index upon standing from the supine (VFI), ejection fraction (EF), ejection volume (EV), residual volume (RV), and residual volume fraction (RVF) were recorded after each protocol. These results were used to compare the lower leg hemodynamic effects of the treatments. RESULTS: Combined ES/VOL single tiptoe exercise produced the highest EV (97.8mL), followed by VOL (80.6mL) and ES (51.7mL) (p < .0008). The EF was also highest for combined ES/VOL (73.1%), followed by VOL (64.5%) and ES (37.8%) (p < .0001). Ten tiptoe ES exercises produced the highest RV (96.2mL), followed by ES/VOL (44.7mL) and VOL (28.2mL) (p < .0001). RVF was also highest in the ES group (71%), followed by ES/VOL (33.4%) and VOL (22.8%) (p < .0001). CONCLUSION: Periodic single ES-induced calf muscle contractions produced significant muscle pump function and could be used to improve venous blood flow and reduce stasis in the lower leg. Continuous ES-induced contractions, on the other hand, could improve lower leg peripheral perfusion while eliciting the physiologic venous muscle pump. Higher RV and RVF after 10 ES-induced contractions in this sample of healthy subjects with normal VFI may be caused by an increase in arterial blood perfusion after repeated ES-induced contractions.

Adult↗