Vagal nerve stimulation (VNS) can treat intractable epilepsy but the epileptolytic mechanism is not known. We have reported a central sympathetic inhibition during VNS (Barnes et al. 2000), but other brainstem and cortical effects remain unknown. Since pulmonary afferent nerves involved in the neural control of respiration might be affected, we studied the relationship between stimulus strength and breathing rate (BR) during VNS.
Seven patients (3 males and 4 females) on VNS treatment due to intractable seizures were enrolled in the study after informed consent and approval of the local Ethics Committee. The VNS system consists of a stimulator (NeuroCybernetic Prosthesis Cyberonics Inc., Texas, USA) placed in the left chest and an electrode wound around the cervical left vagus nerve and tunnelled under the skin to the stimulator. The NeuroScopeTM system (MediFit Diagnostics Ltd, London) monitored brainstem function continuously. MedullaLabTM synchronised breathing movements measured by resistance plethysmography with transcutaneous PO2 and PCO2, non-invasive arterial blood pressure, heart rate, index of cardiac vagal tone and cardiac sensitivity to baroreflex (Julu et al. 2000). Constant currents of 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75 mA and 500 µs duration (250 µs in 2 patients) were applied at 30 Hz in three cycles of 60 s stimulation and 66 s rest in supine position. Breathing movements within 60 s were counted to measure BR and the average of the three cycles was used.
Stimuli below 1 mA had variable effects; depressed BR compared with rest period at 0.25 mA and caused central apnoea of variable lengths between 0.5 and 1 mA. Stimuli above 1 mA increased BR compared with rest period. Rapid shallow breathing was observed in some subjects and all stimuli 250 µs wide caused no apnoea. The average effect in all subjects was increased BR from a baseline of (means ± S.E.M., breaths min-1) 14.6 ± 2.1 to 29 ± 1.3 at 1.75 mA (P < 0.05, Student’s t test). We propose that weak stimuli activate low-threshold, myelinated afferents of the Hering-Breuer inflation reflex to depress BR, while strong stimuli activate thinly myelinated A-δ fibres from lung irritant receptors to increase BR. Stimuli 500 µs wide could activate the unmyelinated fibres from J-type receptors to cause apnoea or rapid shallow breathing (Widdicombe, 1982). The results show that BR can be manipulated by varying stimulus strength. It implies VNS could be used to treat breathing dysrhythmias in brainstem dysfunction such as in Rett syndrome.
- Barnes, A., Duncan, R., Julu, P.O.O., Lindsay, K. & Patterson, J. (2000). J. Physiol. 523.P, 248P.
Julu, P.O.O., Kerr, A.M., Hansen, S., Witt-Engerström, I., Al-Rawas, S., Engerström, L., Apartopoulos, F. & Jamal, G.A. (2000). J. Physiol. 523.P, 254P.
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