Rationale: 

Nerve fiber activation may be a useful biological marker for understanding vagus nerve stimulation (VNS) mechanism of action and optimalisation 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 rats.

Method: 

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, 500msec pulsewidth) varied from 0 to 200 mA.

Intra-operative CAP's were recorded and in/output (I-O) curves, illustrating the relationship between stimulus intensity (input) and the size of the compound 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 a EEG electrode in 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 this 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's were measured intra operatively. Mean value for b intra operatively was 68mA +/- 25mA. At week one, mean b value was 55 mA +/- 12 mA, at week two 43 mA +/-15 mA, at week three 67 mA +/- 30 mA and finally at week four 75 mA +/- 16 mA.

Intra operatively mean c values were 10,3 mA+/- 4,3 mA, at week one 3,4 mA +/-0,9 mA, at week two 4,4 mA+/- 2,6 mA, at week three 3,8 mA +/-1,1 mA and finally at week four 2,8 mA+/- 0,3 mA. 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's were measurable and I-O curves of remained stable over time. Moreover, our CAP data illustrate principle of 'all or nothing' of vagus nerve activation: c values were very small, which indicate 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 all future VNS experiments.