Abstracts

Rationale: Nerve fiber activation may be a useful biological marker for understanding vagus nerve stimulation (VNS) mechanism of action and optimization of VNS parameter choice in clinical practice. This study was performed to evaluate whether compound action potentials (CAP) of the vagus nerve could be measured in a chronic fashion after implantation of a stimulation/recording cuff electrode around the cervical vagus nerve of experimental rats. Methods: Male Wistar rats (N=11) were implanted with a cuff electrode, composed of two rectangular (3x1 mm) platinum stimulation poles, spaced by 1mm and one square (1x1 mm) platinum recording contact at 2 mm rostral of the cathode. Stimulation pulse (bipolar rectangular, 500µsec pulse width) varied from 0 to 200 µA.Intra-operative CAP were recorded and in/output (I-O) curves, illustrating the relationship between stimulus intensity (input) and the size of the evoked potential (output), were determined. All measurements resulted from recording of the 1x1 mm contact in the cuff electrode compared to a ground, which consisted of an EEG electrode in the right occipital skull. CAP measurements were performed every week during 4 weeks after implantation. I-O data were fitted to a Boltzmann sigmoidal function. From these curves we deduced stimulation intensity needed to activate a 50% response (=b) and steepness of the curve (=c), which indicates capacity of nerve activation, i.e. intensity needed to achieve maximal stimulation. Results: In 11 rats, CAP were measured intra-operatively. Mean value for b intra-operatively was 68µA +/- 25µA. At week 1, mean b value was 55 µA +/- 12 µA, at week 2: 43 µA +/-15 µA, at week 3: 67 µA +/- 30 µA and finally at week 4: 75 µA +/- 16 µA. Intra-operatively, mean c values were 10,3 µA+/- 4,3 µA, at week 1: 3,4 µA +/-0,9 µA, at week 2: 4,4 µA+/- 2,6 µA, at week 3: 3,8 µA +/-1,1 µA and finally at week 4: 2,8 µA+/- 0,3 µA. Intensity needed to activate a 50% response and steepness of the curve did not change significantly over time compared to day of surgery. Conclusions: Intra-operative recording of rat vagus nerve CAP with an implantable cuff electrode is feasible. In 6/11 rats CAP were measurable and I-O curves fitted in a Boltzmann sigmoidal function remained stable over time. Moreover, our CAP data illustrate the principle of ‘all or nothing’ of vagus nerve activation: c values were very small, which indicates the existence of a small window between threshold en maximal activation intensity. Finally, CAP measurements can be useful tool as biological marker of stimulation in future VNS experiments. This study was supported by a research grant from Ghent University and by the Clinical Epilepsy Grant Ghent University Hospital"