Vasovagal oscillations and vasovagal responses produced by the vestibulo-sympathetic reflex in the rat

Abstract

Sinusoidal galvanic vestibular stimulation (sGVS) induces oscillations in blood pressure (BP) and heart rate (HR), i.e., vasovagal oscillations, as well as transient decreases in BP and HR, i.e., vasovagal responses, in isoflurane-anesthetized rats. We determined the characteristics of the vasovagal oscillations, assessed their role in the generation of vasovagal responses, and determined whether they could be induced by monaural as well as by binaural sGVS and by oscillation in pitch. Wavelet analyses were used to determine the power distributions of the waveforms. Monaural and binaural sGVS and pitch generated vasovagal oscillations at the frequency and at twice the frequency of stimulation. Vasovagal oscillations and vasovagal responses were maximally induced at low stimulus frequencies (0.025-0.05 Hz). The oscillations were attenuated and the responses were rarely induced at higher stimulus frequencies. Vasovagal oscillations could occur without induction of vasovagal responses, but vasovagal responses were always associated with a vasovagal oscillation. We posit that the vasovagal oscillations originate in a low frequency band that, when appropriately activated by strong sympathetic stimulation, can generate vasovagal oscillations as a precursor for vasovagal responses and syncope. We further suggest that the activity responsible for the vasovagal oscillations arises in low frequency, otolith neurons with orientation vectors close to the vertical axis of the head. These neurons are likely to provide critical input to the vestibulo-sympathetic reflex to increase BP and HR upon changes in head position relative to gravity, and to contribute to the production of vasovagal oscillations and vasovagal responses and syncope when the baroreflex is inactivated.

Keywords: isoflurane anesthesia; otolith; rat; sinusoidal galvanic vestibular stimulation; syncope; wavelet analysis.

Figure 1

Changes in blood pressure (BP) and heart rate (HR) induced by binaural 3 mA sGVS at 0.025 Hz. (A) Vasovagal oscillations and a vasovagal response (VVR) induced by sGVS. Top trace is stimulus (black), middle trace is BP (blue), bottom trace is HR (red). The oscillatory component was at twice the stimulus frequency and was present before and during the transient response. The transient component was characterized by a steep drop in BP and HR that persisted for several minutes. The changes in HR were more pronounced than the changes in BP. Inset on the right is an expanded trace of two cycles (80 s) of sGVS. Arrow indicates location of the data expanded in the inset. BP and HR in the inset are not scaled, to illustrate oscillations at twice the stimulus frequency. (B) In another experiment, the same stimulus induced oscillations at twice the stimulus frequency in both HR and BP (see inset, showing two cycles of sGVS on an expanded trace). This stimulus induced a slight drop in HR, but no prolonged drop in BP.

Figure 2

Monaural sGVS induced by 3 mA sinusoid at 0.025 Hz (A) and 0.1 Hz (B). (A) The 0.025 Hz stimulus (black) induced transient decreases in systolic BP (blue) and HR (red). There were two oscillations in BP and HR for each stimulus cycle (expanded trace on right). (B) A higher stimulus frequency (0.1 Hz) induced only oscillatory components in systolic BP and HR at the frequency of stimulation (expanded trace on right).

Figure 3

Changes in BP and HR induced by single cycles of sGVS at 0.05 Hz (20 s) given (A) binaurally and (B) monaurally. The stimulus was repeated 10 times at 2 min intervals. The data were synchronized from the onset of sGVS. Gray traces – responses to individual stimuli. Blue and red traces – averaged responses for BP and HR, respectively. Vertical dashed lines indicate the onset and offset of sGVS. Horizontal dashed lines show the average BP and HR at the onset of sGVS. Note the double oscillations induced by each sinusoid and the prolonged decline in BP [blue traces in (A,B)] and HR [red traces in (A,B)] over 120 s.

Figure 4

Sinusoidal oscillations in pitch ±70° at (A) 0.025 Hz, (B) 0.05 Hz, and (C) 0.1 Hz. The black trace in each panel is the tilt stimulus; the blue trace is systolic BP. The gray area indicates one tilt cycle. BP oscillated at twice the stimulus frequency at 0.025 and 0.05 Hz, but not at 0.1 Hz.

Figure 5

Vasovagal responses induced by (A) sinusoidal pitching ±70° at 0.025 Hz and (B) static 70° nose-up body tilts. Black trace: stimulus; blue trace: BP; red trace: HR. (A) A vasovagal response was induced by sinusoidal pitching. The onset of the transient changes in BP and HR occurred when the animal was approximately 70° nose-up, as indicated by the vertical dashed line. The vasovagal response, which was initiated when the animal was nose-up, was terminated as the animal approached the prone position. (B) A vasovagal response induced by static nose-up tilt of 70°.

Figure 6

Spontaneous oscillations in BP and HR with no vestibular stimulus. (A) BP and HR recordings. The gray lines represent approximation function median values of BP (blue trace) and HR (red trace). (B) Wavelet decomposition of signals shown in (A) into individual frequency bands. BP (blue traces) is in millimeter of mercury and HR (red traces) is in beats per minute. (C) Power of individual bands of BP (blue) and HR (red) obtained from data shown in (A). (D) Average power of BP (blue) and HR (red) across frequency bands 7–11 in all six rats.

Figure 7

Power of BP, HR, and stimulus of vasovagal oscillation in different frequency bands induced by sGVS and sinusoidal pitching ±70°. The data were obtained at 0.025 Hz (A,C) and 0.1 Hz (B,D). The stimulus power was in a single band [band 11 in (A,C); band 9 in (B,D)]. Most of the power in BP and HR was at the stimulus and at twice the stimulus frequencies. The error bars represent one SD.

Figure 8

Power of BP (A,B) and HR (C,D) at bands containing the stimulus frequency (left column) and twice the stimulus frequency (right column). Data were from six rats tested by sGVS at 0.025 Hz. Only trials that induced vasovagal oscillations (VVO) are shown, from which 34 trials (black circles, group 3) also induced vasovagal responses (VVR). The other 29 trials (gray circles, group 2) had vasovagal oscillations but no vasovagal responses. The abscissa (trial #) represents the order of each trial, is sorted on the magnitude of its power within a specific frequency band. The power in the stimulus frequency band was generally greater when there were vasovagal responses, more so for BP than for HR. However, the power was essentially the same in the double stimulus frequency band regardless of whether there were vasovagal responses or not.