Fig 1.
Effects of Various Sets of Stimulation Parameters on HR, MAP, and CBF.
A representative plot of the stimulator current (mA), heart rate (BPM), mean arterial pressure (mmHg), and cerebral blood flow (perfusion units) is shown. Baseline data was collected for 4 minutes before beginning stimulation (minutes 0–4). Five minutes of recovery was allowed after each stimulation event. Stimulation occurred for 3 minutes using eight different sets of stimulation parameters: 2 mA at 0.025 Hz (I), 4 mA at 0.025 Hz (II), 2 mA at 0.05 Hz (III), 4 mA at 0.05 Hz (IV), 2 mA at 0.1 Hz (V), 4 mA at 0.1 Hz (VI), 2 mA at 0.5 Hz (VII), and 4 mA at 0.5 Hz (VIII). Red lines highlight the start and stop of each stimulation event. The greatest drop in CBF (13.9%) occurred for the 4 mA, 0.025 Hz current (II).
Fig 2.
Representative plot of CBF (bottom, blue plot) changes during sGVS (top, red plot). Baseline CBF (~1780 perfusion units) was collected for 4 minutes before beginning sGVS (at minute 4). Approximately 1 minute after starting sGVS a significant drop in CBF was observed, which was maintained throughout stimulation. After sGVS, CBF recovers, but does not return to baseline values.
Fig 3.
MAP, HR, and CBF Changes Induced by sGVS.
(A) MAP tends to decrease during sGVS (p<0.1). After sGVS, MAP recovers. Prolonged anesthesia causes a steady MAP drop in all rats (Sham: p<0.05 for Baseline vs 10–20 and 20–30 Min Post-Stimulation, p<0.1 for 0–5 Min Post-Stimulation vs 20–30 Min Post-Stimulation; sGVS: p<0.1 between Baseline and 20–30 Min Post-Stimulation). (B) HR is significantly reduced for sGVS rats compared to Sham during sGVS (p<0.05), and for up to 10 Min Post-Stimulation (p<0.05). Prolonged anesthesia causes steady decline of HR in all rats (Sham: p<0.05 for Baseline vs 10–20 and 20–30 Min Post-Stimulation, p<0.05 for 0–5 and 5–10 Min Post-Stimulation vs 10–20 and 20–30 Min Post-Stimulation; sGVS: p<0.05 for Baseline vs each time range post-sGVS, p<0.05 for 0–5 and 5–10 Min Post-Stimulation vs 20–30 Min Post-Stimulation). (C) CBF is significantly reduced during sGVS compared to Sham (p<0.05) and remains depressed for up to 30 minutes post-sGVS (p<0.05). Prolonged anesthesia does not significantly lower CBF in either sham or sGVS rats. * p<0.05 for Sham vs sGVS for the given time variable.
Fig 4.
Behavioral Changes during sGVS in Awake Rats.
Representative images of the changes in behavior observed during sGVS in awake rats. Sinusoidal galvanic vestibular stimulation in the awake animal induces similar symptoms as that experienced by VVS patients. Awake animals during stimulation exhibit signs of fatigue-like behavior (reduced responsiveness and lethargy), labored breathing, altered coordination, and even faint-like behavior (i.e. falling). Representative images from fainting-like behavior in two animals are shown (A, B) with pre-faint-like stance (i), stance during the faint-like behavior (ii), and spontaneous recovery within 1–2 seconds after the onset of the faint-like behavior (iii). (C) Representative images of altered coordination and head swaying.
Fig 5.
Effects of Isoflurane Preconditioning on MAP, HR, and CBF Changes During and Post-sGVS.
(A) MAP is significantly reduced by sGVS in unconditioned and isoflurane preconditioned rats subjected to sGVS compared to Sham (p<0.1 Sham vs sGVS, p<0.05 Sham vs sGVS + Isoflurane PC). MAP recovers immediately upon stopping sGVS, but prolonged anesthesia has a tendency to steadily decrease MAP (Sham: p<0.1 Baseline vs 20–30 Min Post-S-Stimulation; sGVS: p<0.1 Baseline vs 20–30 Min Post-Stimulation). (B) During sGVS, HR is significantly lowered by sGVS in unconditioned and isoflurane preconditioned rats compared to Sham (p<0.05 for Sham vs sGVS and sGVS + Isoflurane PC). HR in unconditioned animals remains decreased for up to 10 minutes post-sGVS, while the HR of isoflurane preconditioned rats recovers after sGVS stops. Prolonged anesthesia causes continued decreased in HR for sham and unconditioned sGVS animals (Sham: p<0.1 between Baseline and 20–30 Min Post-Stimulation; sGVS: p<0.05 for Baseline vs 10–20 and 20–30 Min Post-Stimulation). (C) CBF is reduced by sGVS in unconditioned and isoflurane preconditioned animals compared to Sham (p<0.05 for Sham vs sGVS and sGVS + Isoflurane PC), yet isoflurane preconditioning attenuates the CBF reduction caused by sGVS (p<0.05 sGVS vs sGVS + Isoflurane PC). The CBF reduction caused by sGVS remains for up to 30 minutes post-stimulation (p<0.05 for Sham vs sGVS and sGVS + Isoflurane PC for each time frame Post-Stimulation). * p<0.05 for Sham vs sGVS for the given time variable, # p<0.05 for Sham vs sGVS + Isoflurane PC, & p<0.05 for sGVS vs sGVS + Isoflurane PC.