Electrical stimulation can be used to modulate activity within the nervous system in one of two modes: (1) Activation, where activity is added to the neural signalling pathways, or (2) Block, where activity in the nerve is reduced or eliminated. In principle, electrical nerve conduction block has many attractive properties compared to pharmaceutical or surgical interventions. These include reversibility, localization, and tunability for nerve caliber and type. However, methods to effect electrical nerve block are relatively new. Some methods can have associated drawbacks, such as the need for large currents, the production of irreversible chemical byproducts, and onset responses. These can lead to irreversible nerve damage or undesirable neural responses. In the present study we describe a novel low frequency alternating current blocking waveform (LFACb) and measure its efficacy to reversibly block the bradycardic effect elicited by vagal stimulation in anaesthetised rat model. The waveform is a sinusoidal, zero mean(charge balanced), current waveform presented at 1 Hz to bipolar electrodes. Standard pulse stimulation was delivered through Pt-Black coated PtIr bipolar hook electrodes to evoke bradycardia. The conditioning LFAC waveform was presented either through a set of CorTec® bipolar cuff electrodes with Amplicoat® coated Pt contacts, or a second set of Pt Black coated PtIr hook electrodes. The conditioning electrodes were placed caudal to the pulse stimulation hook electrodes. Block of bradycardic effect was assessed by quantifying changes in heart rate during the stimulation stages of LFAC alone, LFAC-and-vagal, and vagal alone. The LFAC achieved 86.2±11.1% and 84.3±4.6% block using hook (N = 7) and cuff (N = 5) electrodes, respectively, at current levels less than 110 µAp (current to peak). The potential across the LFAC delivering electrodes were continuously monitored to verify that the blocking effect was immediately reversed upon discontinuing the LFAC. Thus, LFACb produced a high degree of nerve block at current levels comparable to pulse stimulation amplitudes to activate nerves, resulting in a measurable functional change of a biomarker in the mammalian nervous system.
Low frequency conduction block: a promising new technique to advance bioelectronic medicines
