We have developed a method to predict excitation of axons based on the response of passive models. An expression describing the transmembrane potential induced in passive models to an applied electric field is presented. Two terms were found to drive the polarization of each node. The first was a source term described by the activating function at the node, and the other was an ohmic term resulting from redistribution of current from sources at other nodes. A total equivalent driving function including both terms was then defined. We found that the total equivalent driving function can be used to provide accurate predictions of excitation thresholds for any applied field. The method requires only knowledge of the intracellular strength-duration relationship of the axon, the passive step response of the axon to an intracellular current, and the values of the extracellular potentials. Excitation thresholds for any given applied field can then be calculated using a simple algebraic expression. This method eliminates the errors associated with use of the activating function alone, and greatly reduces the computation required to determine fiber response to applied extracellular fields.

In this paper we present an analysis of magnetic stimulation of finite length neuronal structures using computer simulations. Models of finite neuronal structures in the presence of extrinsically applied electric fields indicate that excitation can be characterized by two driving functions: one due to field gradients and the other due to fields at the boundaries of neuronal structures. It is found that boundary field driving functions play an important role in governing excitation characteristics during magnetic stimulation. Simulations indicate that axons whose lengths are short compared to the spatial extent of the induced field are easier to excite than longer axons of the same diameter. Simulations also indicate that independent cellular dendritic processes are probably not excited during magnetic stimulation. Analysis of the temporal distribution of induced fields indicates that the temporal shape of the stimulus waveform modulates excitation thresholds and propagation of action potentials.

Background-Approximately 25% of patients who receive an implantable cardioverter-defibrillator (ICD) to treat ventricular tachyarrhythmias have documented atrial tachyarrhythmias before implantation. This study assessed the ability of device-based prevention and termination therapies to reduce the burden of spontaneous atrial tachyarrhythmias. Methods and Results-Patients with a standard indication for the implantation of an ICD and 2 episodes of atrial tachyarrhythmias in the preceding year received a dual-chamber ICD (Medtronic 7250 Jewel AF) that uses pacing and shock therapies for prevention and/or termination of atrial tachyarrhythmias. In a multicenter trial, patients were randomized to 3-month periods with atrial therapies "on" or "off" and subsequently crossed over. Analysis was performed on the 52 of 269 patients who had episodes of atrial tachyarrhythmia and had Ն30 days of follow-up with atrial therapies on and off. The atrial therapies resulted in a reduction of atrial tachyarrhythmia burden from a mean of 58.5 to 7.8 h/mo. A paired analysis (Wilcoxon signed-rank test) showed that the median difference in burden (1.1 h/mo) was highly significant (Pϭ0.007). When the subgroup of 41 patients treated only with atrial pacing therapies was analyzed, the reduction in burden persisted (Pϭ0.01). Conclusions-In this study, patients with a standard ICD indication and atrial tachyarrhythmias had a significant reduction in atrial tachyarrhythmia burden with use of atrial pacing and shock therapies.

1. We have developed a 16-compartment model that reproduces most of the features of the CA1 pyramidal cell electrophysiology observed experimentally. The model was constructed using seven active ionic conductances: gNa, gCa, gDR, gCT, gA, gM, and gAHP whose kinetics have been, inferred, in most cases, from the available voltage-clamp data obtained from these cells. We focussed the simulation on the initial and late accommodation, the slow depolarization potential and the spike broadening during repetitive firing, because their mechanisms are not well understood. 2. Current-clamp records were reproduced by iterative adjustments to the ionic maximum conductances, scaling and/or "reshaping" of the gates' time constant within the experimental voltage-clamp data, and shifting the position of the steady-state gate opening. The final properties of the ionic channels were not significantly different from the voltage-clamp experiments. 3. The resulting model reproduces all four after-potentials that have been recorded to follow activation of the cell. The fast, medium, and slow after-hyperpolarization potentials (AHPs) were, respectively, generated by ICT, IM, and IAHP. Furthermore, the model suggests that the mechanisms underlying the depolarization after potential (DAP) is mostly due to passive recharging of the soma by the dendrites. 4. The model also reproduces most of the firing features experimentally observed during injection of long current pulses. Model responses showed a small initial decrease in the firing frequency during a slow underlying depolarization potential, followed by a more significant frequency decrease. Moreover, a gradual broadening of the action potential and loss of the fast AHP were also observed during the initial high-frequency firing, followed, as the firing frequency decreased, by a gradual recovery of the spikes' original width and fast AHP amplitude increase. 5. A large reduction of the K repolarizing current was required to reproduce the spike broadening and reduction of the fast AHP experimentally observed in CA1 cells during repetitive firing responses. The incorporation of a transient Ca- and voltage-dependent K current (ICT) into the model successfully reproduced these experimental observations. In contrast, we were unable to reproduce this phenomenon when a large persistent Ca- and voltage-dependent K current (generally named IC) was included in the model. These results suggest that there is a strong contribution to action-potential repolarization and fast AHP by a transient Ca- and voltage-dependent K current (ICT). 6. The two accommodation steps were induced by a progressively enlargement of two K currents IM (initial) and IAHP (late).(ABSTRACT TRUNCATED AT 400 WORDS)

for the Worldwide Jewel AF Investigators Background-Although overdrive pacing for treating atrial flutter is well established, the efficacy of device-based atrial pacing for treating spontaneous atrial tachyarrhythmias in patients with implantable cardioverter defibrillators (ICD) is unknown. This study evaluated the efficacy of novel pacing therapies for treating atrial tachyarrhythmias in patients receiving a dual-chamber ICD to treat ventricular tachyarrhythmias. Methods and Results-A Jewel AF ICD was implanted in 537 patients with ventricular arrhythmia who were followed for 11.4Ϯ8.2 months (74% had a documented history of atrial tachyarrhythmias). The device discriminated atrial tachycardia (AT) from atrial fibrillation (AF) on the basis of cycle length and regularity, and it used 3 different methods of overdrive atrial pacing (Ramp, Burstϩ, and 50-Hz burst) to treat AT episodes and one method (50-Hz burst) to treat AF episodes. Pacing successfully terminated 59% of 1500 spontaneous AT episodes in 127 patients and 30% of 880 AF episodes in 101 patients (PϽ0.001). With AT and AF episodes combined, pacing efficacy was 48%. Pacing efficacy was significantly reduced at AT cycle lengths Յ220 ms and AF cycle lengths Յ160 ms (PϽ0.01) The median time from pacing to AT/AF termination was 1.1 minute for the pacing successes and 96 minutes for the failures (PϽ0.001). Conclusions-Atrial