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Application of models of defibrillation to human defibrillation data: implications for optimizing implantable defibrillator capacitance.

BACKGROUND: Theoretical models predict that optimal capacitance for implantable cardioverter-defibrillators (ICDs) is proportional to the time-dependent parameter of the strength-duration relationship. The hyperbolic model gives this relationship for average current in terms of the chronaxie (t(c)). The exponential model gives the relationship for leading-edge current in terms of the membrane time constant (tau(m)). We hypothesized that these models predict results of clinical studies of ICD capacitance if human time constants are used. METHODS AND RESULTS: We studied 12 patients with epicardial ICDs and 15 patients with transvenous ICDs. Defibrillation threshold (DFT) was determined for 120-microF monophasic capacitive-discharge pulses at pulse widths of 1.5, 3.0, 7.5, and 15 ms. To compare the predictions of the average-current versus leading-edge-current methods, we derived a new exponential average-current model. We then calculated individual patient time parameters for each model. Model predictions were validated by retrospective comparison with clinical crossover studies of small-capacitor and standard-capacitor waveforms. All three models provided a good fit to the data (r2=.88 to .97, P<.001). Time constants were lower for transvenous pathways (53+/-7 omega) than epicardial pathways (36+/-6 omega) (t(c), P<.001; average-current tau(m), P=.002; leading-edge-current tau(m), P<.06). For epicardial pathways, optimal capacitance was greater for either average-current model than for the leading-edge-current model (P<.001). For transvenous pathways, optimal capacitance differed for all three models (P<.001). All models provided a good correlation with the effect of capacitance on DFT in previous clinical studies: r2=.75 to .84, P<.003. For 90-microF, 120-microF, and 150-microF capacitors, predicted stored-energy DFTs were 3% to 8%, 8% to 16%, and 14% to 26% above that for the optimal capacitance. CONCLUSIONS: Model predictions based on measured human cardiac-muscle time parameter have a good correlation with clinical studies of ICD capacitance. Most of the predicted reduction in DFT can be achieved with approximately 90-microF capacitors.

Defibrillators, Implantable↗

Optimal small-capacitor biphasic waveform for external defibrillation: influence of phase-1 tilt and phase-2 voltage.

BACKGROUND: Biphasic waveforms have been reported to be more efficacious than monophasic waveforms for external defibrillation. This study examined the optimal phase-1 tilts and phase-2 leading-edge voltages with small capacitors (60 and 20 microF) for external defibrillation. We also assessed the ability of the "charge-burping" model to predict the optimal waveforms. METHODS AND RESULTS: Two groups of studies were performed. In group 1, 9 biphasic waveforms from a combination of 3 phase-1 tilt values (30%, 50%, and 70%) and 3 phase-2 leading-edge voltage values (0.5, 1.0, and 1.5 times the phase-1 leading-edge voltage, V1) were tested. Phase-2 pulse width was held constant at 3 ms in all waveforms. Two separate 60- microF capacitors were used in each phase. The energy value that would produce a 50% likelihood of successful defibrillation (E50) decreased with increasing phase-1 tilt and increased with increasing phase-2 leading-edge voltage except for the 30% phase-1 tilt waveforms. In group 2, 9 waveforms were identical to the waveforms in group 1, except for a 20- microF capacitor for phase 2. E50 decreased with increasing phase-1 tilt. Phase-2 leading-edge voltage of 1.0 to 1.5 V1 appeared to minimize E50 for phase-1 tilt of 50% and 70% but worsened E50 for phase-1 tilt of 30%. There was a significant correlation between E50 and residual membrane voltage at the end of phase 2, as calculated by the charge-burping model in both groups (group 1, R2=0.47, P<0.001; group 2, R2=0.42, P<0.001). CONCLUSIONS: The waveforms with 70% phase-1 tilt were more efficacious than those with 30% and 50%. The relationship of phase-2 leading-edge voltage to defibrillation efficacy depended on phase-2 capacitance. The charge-burping model predicted the optimal external biphasic waveform.

Animals↗

Electrophysiologic properties of aneurally cultured muscle from patients with myotonic muscular atrophy.

Electrophysiologic studies were performed on aneurally cultured human muscle cells from seven patients with myotonic muscular atrophy and seven controls. There was no significant difference in resting membrane potential. When the cells were hyperpolarized to -80 mV, there was no significant difference in effective membrane resistance, effective membrane capacitance, normalized membrane conductance, membrane threshold, action potential amplitude, or maximum rate of rise of the action potential. Repetitive discharges were elicited by anodal-break excitation in a few cells from each group. We found no evidence that cultured myotonic atrophy muscle cells are electrically different from control cells.

Action Potentials↗

Capacitive coupled stray currents during laparoscopic and endoscopic electrosurgical procedures.

Capacitively coupled currents may not be appreciated during laparoscopic and endoscopic radiofrequency electrosurgery. Two specific problems are documented and quantified: coupling of current into metal trocar cannulas during laparoscopic surgery and coupling of current into a guide wire during endoscopic surgery. The examples can yield power levels in excess of 25 watts (laparoscopic) and 15 watts (endoscopic) on nearby metal conductors, which can in turn be dissipated into patient organs such as the bowel or the common bile duct. This capacitive coupling can be, in part, responsible for serious patient complications. Methods to minimize capacitive coupling, e.g., active electrode shielding, dispersive metal cannulas, sheathed guide wires, and bipolar active electrodes, are discussed for each example.

Electric Conductivity↗

A computer model of hemorrhagic shock in domestic swine.

We used a modified version of the computer model of the circulation developed by C.V. Greenway (Pharmacol Rev 33:213-251, 1982) to study the volume-pressure relationship of the systemic venous circulation during and immediately after massive blood loss. Our theoretical predictions were based on experimental measurements performed in conscious, chronically instrumented swine subjected to massive and rapid loss of a predetermined amount of blood. These animals were subjected to an exponential removal of either 50% of their calculated blood volume in 1 hour or a linear removal of 60% in 15 minutes. Our computer model indicates a hysteresis effect between the volume-pressure curves during and immediately following hemorrhage. The results emphasize the importance of venous capacitance changes as a compensatory response to blood loss.

Animals↗

Sympathetic vascular control of the pig nasal mucosa: (I). Increased resistance and capacitance vessel responses upon stimulation with irregular bursts compared to continuous impulses.

An in vivo model is described in which pentobarbital anaesthetized pigs were used to study the sympathetic nervous control of the nasal mucosal vascular bed. Changes in blood flow in the sphenopalatine artery (representing nasal blood flow) and in the volume of the nasal cavity (mainly reflecting blood content in venous sinusoids), upon electrical stimulation of the cervical sympathetic trunk, were recorded simultaneously. Single impulses (15V, 5 ms) reduced both the arterial flow and the volume of the nasal mucosa. The effects of nerve stimulation with a continuous train of impulses at 0.59, 2 and 6.9 Hz were compared with those caused by stimulation with the irregular bursting pattern, triggered by recorded human sympathetic vasoconstrictor nerve activity, with the same average frequencies. Both types of stimulation reduced nasal blood flow and volume, but the responses were significantly larger with burst stimulation at 0.59 Hz. The volume reduction was already maximal at 0.59 Hz while the blood flow response increased further higher frequencies. Local intra-arterial pretreatment with the alpha-adrenoceptor antagonist phenoxybenzamine significantly attenuated the flow and volume responses to single impulses, while clear-cut reductions in blood flow (by 40%) and volume (by 80%) remained, upon stimulation, at 6.9 Hz. Noradrenaline given intra-arterially caused a dose-dependent reduction in nasal blood flow and volume. The noradrenaline effects were blocked by phenoxybenzamine treatment. The results show that the pig nasal mucosa represents a model where both blood flow and volume changes can be studied in parallel in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of phlorizin and phloretin on passive and dynamic electrical properties in muscle membrane.

The effects of phlorizin and phloretin on the cable properties were investigated in frog sartorius muscle by conventional cable analysis. Actions of phloretin on voltage-dependent ionic conductances were also studied by analysis of the phase plane trajectories. Both drugs evoked a significant decrease in specific membrane resistance (Rm) in chloride-containing Ringer's solution. The linear membrane capacitance increased by about 30%. On the contrary, in the presence of the non-penetrating anion, glutamate, a slight increase in Rm was induced by phlorizin. It is suggested that these drugs may increase the chloride conductance in the muscle membrane. Under the effect of phloretin the resting membrane potential remained unchanged but the amplitude of the action potential was lowered and the rate of repolarization was significantly reduced. The rate of depolarization during the "foot" of the action potential and the conduction velocity calculated from the rate constant of depolarization decreased. The maximum Na conductance was not altered by phloretin but K conductance was reduced. The time constant (tau K) reflecting the kinetic properties of K conductance was increased about seven-fold. It is suggested that great importance may be attributed to the dipole properties of these drugs in the actions presented above.

Action Potentials↗

Review of mechanisms by which electrical stimulation alters the transmembrane potential.

Electrical stimuli pace, cardiovert, or defibrillate the heart by changing transmembrane potential (deltaVm). Recent simulation studies provide insights into mechanisms by which stimuli establish deltaVm. This review attempts a nonmathematical description of these mechanisms. We start with the cable model in which the intracellular core conductor is bounded by a highly resistive and capacitive membrane that separates the intracellular and extracellular spaces. Intracellular and extracellular resistances are assumed to vary linearly with position. Although this model predicts anodal extracellular stimuli hyperpolarize adjacent tissue and cathodal extracellular stimuli depolarize that tissue, it fails to reproduce regions of opposite deltaVm distant from the electrodes. We then consider the sawtooth model in which microscopic discontinuities in intracellular resistance represent gap junctions. While model studies with such discontinuities demonstrate large deltaVm at cell ends, experimental validation of such deltaVm remains elusive. Extending the analysis to the two- and three-dimensional syncytium, we also consider the bidomain model in which intracellular, extracellular, and interstitial currents are explicitly characterized. Differences in resistance to these currents gives rise to virtual electrodes, which are experimentally observed regions of large deltaVm that arise distant from the stimulating electrode. Distant deltaVm regions are also evident when macroscopic discontinuities in intracellular resistance are introduced into the bidomain model. Such discontinuities are associated with clefts or scars that give rise to "secondary sources." Albeit the cable model offers remarkable insight the bidomain model and the concept of secondary sources provide a more complete understanding of membrane excitation, especially when combined into a unifying activating function.

Action Potentials↗

Application of a non-invasive method to study the moisturizing effect of formulations containing vitamins A or E or ceramide on human skin.

Moisturizers containing vitamins A and E as well as ceramides are believed to improve the skin condition by increasing the water content of the stratum corneum. The aim of this research was to evaluate, through the capacitance method (a non-invasive method), the moisturizing effect of an O/W emulsion (non-ionic self-emulsifying base) containing vitamin A palmitate, vitamin E acetate, and ceramide III on human skin. The studies were carried out on a group of 40 healthy Caucasian female test subjects between 30 and 45 years of age, using the Corneometer CM 825 PC. Skin measurements were taken from the volunteers at 7 and 30 days after daily use (twice a day) of the tested products. The presence of vitamins A and E or ceramide III did not cause an improvement in the hydration of the stratum corneum, which means that none of those compounds strengthens the hydration effectiveness of the base formulations used, at least at the doses tested. The interpretation of electrical measurement regarding skin moisture should be made with caution; thus the results observed in this study show the importance of using different approaches (or methodologies) to verify the performance of the formulas tested. We conclude that, at the low doses typically used in cosmetic formulations, vitamins A and E and ceramide III are not likely to contribute to the hydrating effects of the base moisturizing formulation when assessed by capacitance.

Ceramides↗

A broadband system for multifrequency static imaging in electrical impedance tomography.

A widely accepted method for static imaging in electrical impedance tomography (EIT) is to measure at two frequencies. The choice of measurement frequencies is application-dependent because some different tissues cannot be distinguished when using two fixed frequencies. We have developed a system that generates signals from 8-10(3) kHz and applies two of these signals simultaneously to the body through a broadband current mirror. Great care has been taken in the design of the current injection multiplexer in order to keep the current source output capacitance as low as possible. Furthermore design of the layout of the patient interface board, in order to reduce feedthrough capacitances, also needs great care. Other parameters for driving and detection sections have been designed according to our results from FEM and circuit simulations including skin and electrode effects. Simulations using FEM with available tissue impedance data and preliminary measurements in a discrete phantom show that static imaging is possible for both the real and imaginary parts of the impedance.

Electric Conductivity↗

A new algorithm for voltage clamp by iteration: a learning control of a nonlinear neuronal system.

Voltage-clamp of excitable membrane allows the measurement of membrane currents associated with electrical potential changes across the membrane. However, it has been impossible in practice to apply the conventional analog feedback voltage-clamp circuits to single electrode voltage clamping in central neurons. The reason for this is that the feedback system becomes unstable because of the positive feedback required for compensation of capacitative loss through the wall of the microelectrode. Park et al. (1981) proposed a new iterative technique to solve this problem. It requires that the potential to be clamped repeats itself with little or no change. The amount of current needed to clamp the membrane potential is not determined at once, but in a step-wise, trial and error fashion in the course of a set of repetitions. Since the feedback loop is open in real time, the system has great stability, and this advantage can be exploited in single electrode preparations. The computation algorithm which calculates the current waveform based on the voltage deviation during the last trial is the central part of the iterative voltage-clamp system. In this paper, we propose a new algorithm, which has several theoretical and practical advantages over the original one proposed by Park et al. First, two parameters used in the new algorithm are predetermined by a current-clamp experiment. Second, the speed of convergence of the new algorithm is faster than that of the Park's original algorithm. This was shown by computer simulation of iterative voltage clamp of artificial membrane following Hodgkin-Huxley equations for squid axon membrane and Rall's compartment model for a neuron with dendrites. Finally, we offer proof that the new algorithm is certain to converge for the general cases of voltage-clamp experiments with active membrane properties, synaptic membranes, etc. Consequently, the new algorithm for iterative voltage clamp is very suitable for single electrode voltage clamp in the central neurons. The new algorithm has been successfully applied to voltage-clamp experiments on rubrospinal neurons of cats (Tsukahara, Murakami, Kawato, Oda, and Etoh, in preparation).

Animals↗

Modification of sodium channel currents by lanthanum and lanthanide ions in human heart cells.

I examined the effects of 100 microM extracellular lanthanum and lanthanide ions on the fast transmembrane sodium channel currents of human heart cell segments. The experiments were conducted under control of the transmembrane electrical and chemical gradients. Lanthanum and lanthanide ion exposure decreased the amplitude and increased the inactivation time constant of the sodium current. Only a transient increase occurred for the activation time constant of the sodium current. The dependence of peak sodium current on excitatory and holding potentials (steady-state activation and inactivation curves, respectively) was transiently shifted to less negative potentials during the first 3 min of exposure, as if these cations were momentarily neutralizing the effective negative charges at the extracellular side of the membrane. The curves then returned to their original position and only the inactivation curves continued shifting progressively towards a limit at more negative membrane potentials. Membrane capacitance was always reduced and this may explain these late effects in terms of changes in membrane dielectric properties and free and bound charges, in addition to traditional screening and binding concepts. These effects were related to the electronic structure of these ions.

Aging↗

Measurement of sealing resistance of cell-electrode interfaces in neuronal cultures using impedance spectroscopy.

Sealing resistance is highly significant with respect to the electrical neuron-electrode contact because it decreases the stimulation threshold of neurons cultured on a planar micro-electrode array. A method is proposed for measurement of the sealing resistance using impedance spectroscopy. The effect of the sealing resistance on the total impedance spectrum of a cell-electrode interface is modelled for complete coverage of the electrode by the cell. Sensitivity analysis demonstrates that the impedance spectrum is determined by four parameters: two electrode parameters, the sealing resistance and the shunt capacitance between the lead of the electrode and the culture medium. Experimental verification of the model is performed by simultaneous measurement of the impedance spectrum and electrode coverage. A good and unique fit between the simulated and measured impedance spectra was obtained by varying the two electrode parameters and the sealing resistance.

Animals↗

Passive electrical properties of rod outer segments.

1. Measurements on a packed suspension of randomly oriented, dark-adapted frog rods at frequencies of 15 c/s-0.5 Mc/s indicate a behaviour similar to that of other biological materials.2. Results are analysed on the assumption that the low-frequency limiting resistance is determined by current flowing in the suspending medium and that, of the rods, two thirds are oriented perpendicular to the applied field and one third parallel to it. Those parallel to the field are treated as non-conductors.3. From the high-frequency limiting resistance the conductivity of the rod interior is calculated to vary linearly with the conductivity of the medium. The slope of the relation of internal to external conductivity is 0.50 with a limiting internal conductivity (at zero external) of 280 mumho/cm.4. On the assumption that the suspension can be represented as a single-capacitance network, the characteristic frequency of impedance is used to calculate a capacitance for the rod surface of 1.54 muF/cm(2). On the assumption of a distribution in properties of the suspension according to the theory of Bruggeman, the capacitance is calculated to have a value of about one half this.5. At frequencies below 5 kc/s the impedance locus deviates from the curve describing the behaviour at higher frequencies. It is suggested that this may involve conduction in a thin layer extending along the surface of the rod.

Animals↗

Effect of glucocorticoid treatment on the excitability of rat skeletal muscle.

Dexamethasone treatment in the rat produced depolarization of extensor digitorum longus (EDL) muscle fibers but not soleus (SOL) fibers studied in vitro at 23 degrees C. The depolarization of EDL fibers was most prominent after 1 day of treatment (treated -77.5 +/- 1.1 mV, control -87.2 +/- 0.8 mV; mean +/- S.E.), and was associated with elevation of the action potential threshold and reduction of the action potential overshoot. In vivo, or in vitro in chloride-free solution, the resting potential and action potential threshold and overshoot of EDL fibers from glucocorticoid-treated and control rats were similar. Sodium currents were studied with a patch voltage clamp. Glucocorticoid treatment did not alter the voltage dependence of sodium channel activation or inactivation in fast twitch muscle fibers. Maximal inward currents occurred at about -29 mV and half-maximal inward currents at about -50 mV. Sodium channels were half inactivated at about -71 mV. Glucocorticoid treatment did not alter the sarcolemmal resistance or capacitance. We conclude that glucocorticoid treatment does not produce muscle weakness or atrophy by altering the excitability of muscle fibers.

Action Potentials↗

Detection of transient capacitance increase associated with channel formation in lipid bilayers.

The insertion of alpha- and beta-latrotoxins and sea anemone (Radianthus macrodactilus) toxin into bilayer lipid membranes (BLMs) was investigated using the method of simultaneous conductance/capacitance measurement. All the toxins investigated induced capacitance changes which preceded toxin-induced conductance increases. The processes that may underlie the observed effect are discussed.

Animals↗

Frequency domain analysis of membrane capacitance of cultured cells (HeLa and myeloma) using the micropipette technique.

The membrane capacitance and conductance of cultured cells (HeLa and mouse myeloma) are investigated using the micropipette method. Mean values of the membrane capacities were found to be 1.9 microF/cm2 for HeLa cells and 1.0 microF/cm2 for myeloma cells. These values are in agreement with those obtained using the suspension method. Whereas the suspension method is unable to provide the information on membrane conductance, the micropipette method is able to measure even an extremely small membrane conductance if leakage current is negligibly small. The membrane conductances were found, using this technique, to be approximately 90-100 microS/cm2 for both HeLa and myeloma cells. One of the purposes of this study is to establish the frequency profile of membrane capacitance. It was found, however, that membrane capacitances of these cells are independent of frequency between 1 Hz and 1 KHz within the resolution of this technique.

Animals↗

A prospective randomized comparison in humans of 90-mu F and 120-mu F biphasic pulse defibrillation using a unipolar defibrillation system.

INTRODUCTION: Capacitance is known to influence defibrillation. Optimal biphasic waveform capacitance for transvenous unipolar defibrillation systems in man is currently being defined. In an effort to improve defibrillation efficacy, we examined the relative defibrillation efficacy of a 65% tilt biphasic pulse from a 90-mu F capacitor compared to a 65% tilt biphasic pulse from a 120-mu F capacitor in a prospective, randomized fashion in 16 consecutive cardiac arrest survivors undergoing defibrillator surgery. METHODS AND RESULTS: The transvenous unipolar pectoral defibrillation system uses a single endocardial RV anodal defibrillation coil and the shell of an 80-cc volume (88 cm2 surface area) pulse generator (Medtronic Model 7219C PCD "active CAN") as the cathode for the first phase of the biphasic shock: RV+ --> CAN-. Defibrillation thresholds for each capacitance were determined prospectively in a randomized fashion. The defibrillation threshold results for the 90-mu F capacitance were: leading edge voltage 383 +/- 132 V; stored energy 7.4 +/- 5.0 J; and resistance 57 +/- 10 omega. The results for the 120-mu F capacitance were: leading edge voltage 315 +/- 93 V (P = 0.002); stored energy 6.5 +/- 3.7 J (P = 0.21); and resistance 57.0 +/- 11 omega (P = 0.87). CONCLUSIONS: We conclude that 90-mu F, 65% tilt biphasic pulses used with unipolar pectoral defibrillation systems have equivalent stored energy defibrillation efficacy compared to 120-mu F, 65% tilt pulses. Use of lower capacitance is possible in present implantable defibrillators without compromising defibrillation.

Adult↗