Tina Vrabec

Alternating current and infrared produce an onset-free reversible nerve block.

Abstract. Nerve block can eliminate spasms and chronic pain. Kilohertz frequency alternating current (KHFAC) produces a safe and reversible nerve block. However, KHFAC-induced nerve block is associated with an undesirable onset response. Optical inhibition using infrared (IR) laser light can produce nerve block without an onset response, but heats nerves. Combining KHFAC with IR inhibition [alternating current and infrared (ACIR)] produces a rapidly reversible nerve block without an onset response. ACIR can be used to rapidly and reversibly provide onset-free nerve block in the unmyelinated nerves of the marine mollusk Aplysia californica and may have significant advantages over either modality alone. ACIR may be of great clinical utility in the future.

Bioelectronic neuromodulation of the paravertebral cardiac efferent sympathetic outflow and its effect on ventricular electrical indices

BACKGROUND Neuromodulation of the paravertebral ganglia by using symmetric voltage controlled kilohertz frequency alternating current (KHFAC) has the potential to be a reversible alternative to surgical intervention in patients with refractory ventricular arrhythmias. KHFAC creates scalable focal inhibition of action potential conduction. OBJECTIVE The purpose of this article was to evaluate the efficacy of KHFAC when applied to the T1-T2 paravertebral chain to mitigate sympathetic outflow to the heart. METHODS In anesthetized, vagotomized, porcine subjects, the heart was exposed via a midline sternotomy along with paravertebral chain ganglia. The T3 paravertebral ganglion was electrically stimulated, and activation recovery intervals (ARIs) were obtained from a 56-electrode sock placed over both ventricles. A bipolar Ag electrode was wrapped around the paravertebral chain between T1 and T2 and connected to a symmetric voltage controlled KHFAC generator. A comparison of cardiac indices during T3 stimulation conditions, with and without KHFAC, provided a measure of block efficacy. RESULTS Right-sided T3 stimulation (at 4 Hz) was titrated to produce reproducible ARI changes from baseline (52 ± 30 ms). KHFAC resulted in a 67% mitigation of T3 electrical stimulation effects on ARI (18.5 ± 22 ms; P < .005). T3 stimulation repeated after KHFAC produced equivalent ARI changes as control. KHFAC evoked a transient functional sympathoexcitation at onset that was inversely related to frequency and directly related to intensity. The optimum block threshold was 15 kHz and 15 V. CONCLUSION KHFAC applied to nexus (convergence) points of the cardiac nervous system produces a graded and reversible block of underlying axons. As such, KHFAC has the therapeutic potential for on-demand and reversible mitigation of sympathoexcitation.

Bioelectronic block of paravertebral sympathetic nerves mitigates post–myocardial infarction ventricular arrhythmias

BACKGROUND Autonomic dysfunction contributes to induction of ventricular tachyarrhythmia (VT). OBJECTIVE To determine the efficacy of charge-balanced direct current (CBDC), applied to the T1-T2 segment of the paravertebral sympathetic chain, on VT inducibility post-myocardial infarction (MI). METHODS In a porcine model, CBDC was applied in acute animals (n = 7) to optimize stimulation parameters for sympathetic blockade and in chronic MI animals (n = 7) to evaluate the potential for VTs. Chronic MI was induced by microsphere embolization of the left anterior descending coronary artery. At termination, in anesthetized animals and following thoracotomy, an epicardial sock array was placed over both ventricles and a quadripolar carousel electrode positioned underlying the right T1-T2 paravertebral chain. In acute animals, the efficacy of CBDC carousel (CBDCC) block was assessed by evaluating cardiac function during T2 paravertebral ganglion stimulation with and without CBDCC. In chronic MI animals, VT inducibility was assessed by extrasystolic (S1-S2) stimulations at baseline and under >66% CBDCC blockade of T2-evoked sympathoexcitation. RESULTS CBDCC demonstrated a current-dependent and reversible block without impacting basal cardiac function. VT was induced at baseline in all chronic MI animals. One animal died after baseline induction. Of the 6 remaining animals, only 1 was reinducible with simultaneous CBDCC application (P < .002 from baseline). The ventricular effective refractory period (VERP) was prolonged with CBDCC (323 ± 26 ms) compared to baseline (271 ± 32 ms) (P < .05). CONCLUSIONS Axonal block of the T1-T2 paravertebral chain with CBDCC reduced VT in a chronic MI model. CBDCC prolonged VERP, without altering baseline cardiac function, resulting in improved electrical stability.

Continuous Direct Current Nerve Block Using Multi Contact High Capacitance Electrodes

Charge-balanced direct current (CBDC) nerve block can be used to block nerve conduction in peripheral nerves. Previous work demonstrated that the CBDC waveform could be used to achieve a 10% duty cycle of block to non-block repeatedly for at least two hours. We demonstrate that the duty cycle of this approach can be significantly increased by utilizing multiple electrode contacts and cycling the CBDC waveform between each contact in a “carousel” configuration. Using this approach, we demonstrated in an acute rat sciatic nerve preparation, that a 30% duty cycle complete block can be achieved with two contacts; and a 100% duty cycle block (>95% complete block) can be achieved with four contacts. This latter configuration utilized a 4-s block plateau, with 3 s between successive plateaus at each contact and a recharge phase amplitude that was 34% of the block amplitude. Further optimization of the carousel approach can be achieved to improve block effectiveness and minimize total electrode length. This approach may have significant clinical use in cases where a partial or complete block of peripheral nerve activity is required. In one example case, we achieved continuous block for 22 min without degradation of nerve conduction. Future study will be required to further optimize this technique and to demonstrate safety for chronic human use.

Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block.

OBJECTIVE Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. APPROACH A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability. MAIN RESULTS The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p < 0.001). The area under the force curve was reduced from 6.8 Ns (range: 3.5-21.9 Ns) to 0.54 Ns (range: 0.18-0.86 Ns) (p < 0.01). No change in nerve conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms. SIGNIFICANCE The distal application of CBDC can significantly reduce or even completely prevent the KHFAC onset response without a change in nerve conductivity.

A novel waveform for No-Onset nerve block combining direct current and kilohertz frequency alternating current

Kilohertz frequency alternating current (KHFAC) has been shown to produce a fast acting, reversible nerve block. The principal drawback to this technique is a short, but intense burst of firing at the initiation of the KHFAC which is referred to as the “onset response”. The “onset response” can be eliminated by the use of a second electrode which delivers direct current (DC) briefly during the onset duration. However, the DC cannot be delivered for a sufficiently long time to suppress the onset without causing damage to the nerve. High surface area electrodes have been developed which can be used to deliver DC for long enough to eliminate the onset without causing damage. Furthermore, instead of using multiple electrodes to create a no onset block, the DC and KHFAC are combined in novel waveform which can be output on a single monopolar electrode. This novel waveform has been demonstrated to prevent onset in both simulation and in an in vivo rat sciatic nerve model.

A Rapid Prototyping Environment for Neuroprotheses

A rapid prototyping environment for functional electrical stimulation has been developed with goals of facilitating the exploration of new concepts in neuroprosthetic control and simplifying the process of moving controllers from the laboratory to the home setting. Using the system, rehabilitation engineers can develop controllers as block diagrams, without the involvement of a software engineer. The system is successfully controlling the upper extremities of four people with spinal cord injuries

Temporary persistence of conduction block after prolonged kilohertz frequency alternating current on rat sciatic nerve

OBJECTIVE Application of kilohertz frequency alternating current (KHFAC) waveforms can result in nerve conduction block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5-10 min. This study investigated the effect of repeated and prolonged application of KHFAC on rat sciatic nerve with bipolar platinum electrodes. APPROACH Varying durations of KHFAC at signal amplitudes for conduction block with intervals of no stimulus were studied. Nerve conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a blocking electrode. The PS signal traveled through the block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of conduction patency of the nerve in the block zone. MAIN RESULTS Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 min. They fell significantly but recovered to near pre-block levels for cumulative stimulus of 50  ±  20 min, for the tested On/Off times and frequencies. Conduction recovered in two phases, an initial fast one (60-80% recovery), followed by a slower phase. No permanent conduction block was seen at the end of the observation period during any experiment. SIGNIFICANCE This carry-over block effect may be exploited to provide continuous conduction block in peripheral nerves without continuous application of KHFAC.OBJECTIVE Application of Kilohertz Frequency Alternating Current (KHFAC) waveforms can result in nerve conduction block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5 - 10 minutes. This study investigated the effect of repeated and prolonged application of KHFAC on rat Sciatic nerve with bipolar platinum electrodes. Approach: Varying durations of KHFAC at signal amplitudes for conduction block with intervals of no stimulus were studied. Nerve conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a blocking electrode. The PS signal traveled through the block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of conduction patency of the nerve in the block zone. Main Results: Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 minutes. They fell significantly but recovered to near pre-block levels for cumulative stimulus between 50 +/- 20 minutes, for the tested On / Off times and frequencies. Conduction recovered in two phases, an initial fast one (60 -80% recovery), followed by a slower phase. No permanent conduction block was seen at the end of the observation period during any experiment. Significance: This Carry-over Block Effect (COBE) may be exploited to provide continuous conduction block in peripheral nerves without continuous application of KHFAC. .

Electrodes for electrical conduction block of the peripheral nerve

Abstract Many neurological disorders are caused by pathological neuronal firing leading to adverse effects mediated through the innervated end organs. Examples are chronic pain, motor impairments, abnormal postures of the limb and torso, and spasticity due to lesions in the brain or the spinal cord. These pathologies are manifested in stroke, traumatic brain injury, spinal cord injury, cerebral palsy, multiple sclerosis, and amputation neuromas. Medical treatment is based on a hierarchy of increasingly invasive modalities. There is still a need for a reliable, fast-acting, nontoxic, and reversible method of nerve block for many of these neurological conditions. Kilohertz frequency alternating current nerve block and direct current nerve block offer this type of therapy. This chapter describes the design of nerve based electrodes that are suitable for these two types of electrical nerve block.