Differential hemodynamic and respiratory responses to right and left cervical vagal nerve stimulation in rats

Neuromodulation through vagal nerve stimulation (VNS) is currently explored for a variety of clinical conditions. However, there are no established VNS parameters for animal models of human diseases, such as hypertension. Therefore, the aim of this study was to assess hemodynamic and respiratory responses to right- or left-sided cervical VNS in a hypertensive rat model. Anesthetized stroke-prone spontaneously hypertensive rats were instrumented for arterial blood pressure and heart rate monitoring and left- or right-sided VNS Cervical VNS was applied through bipolar coil electrodes. Stimulation parameters tested were 3 V and 6 V, 2 Hz to 20 Hz stimulation frequency, and 50 μsec to 20 msec pulse duration. Each combination of stimulation parameters was applied twice with altered polarity, that is, anode and cathode in the cranial and caudal position. Respiration rate was derived from systolic blood pressure fluctuations. In general, cervical VNS caused bradycardia, hypotension, and tachypnea. These responses were more pronounced with left-sided than with right-sided VNS and depended on the stimulation voltage, stimulation frequency, and pulse duration, but not on the polarity of stimulation. Furthermore, the results suggest that at low stimulation frequencies (<5 Hz) and short pulse durations (<0.5 msec) primarily larger A-fibers are activated, while at longer pulse durations (>0.5 msec) smaller B-fibers are also recruited. In conclusion, in rats left-sided cervical VNS causes greater cardio-respiratory responses than right-sided VNS and at lower stimulation frequencies (e.g., 5 Hz), longer pulse durations (>0.5 msec) seem to be required to consistently recruit B-fibers in addition to A-fibers.