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

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ABSTRACT

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.

No MeSH data available.


Changes (Δ) in heart rate (HR0, mean arterial blood pressure (MAP), and respiratory frequency (RF) in response to left‐ (closed circles, n = 3) or right‐sided (open circles, n = 4) cervical vagal nerve stimulation using increasing stimulation frequencies (x‐axes) of charge balanced rectangular impulses of 3 V and pulse durations of 0.1 msec (left) or 1.0 msec (right). Absolute baseline values are provided in Table 2. *: P < 0.05 for difference of absolute values at the respective stimulation frequency and preceding baseline. No significant differences were detected between right and left vagal nerve stimulation (VNS).
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phy213244-fig-0003: Changes (Δ) in heart rate (HR0, mean arterial blood pressure (MAP), and respiratory frequency (RF) in response to left‐ (closed circles, n = 3) or right‐sided (open circles, n = 4) cervical vagal nerve stimulation using increasing stimulation frequencies (x‐axes) of charge balanced rectangular impulses of 3 V and pulse durations of 0.1 msec (left) or 1.0 msec (right). Absolute baseline values are provided in Table 2. *: P < 0.05 for difference of absolute values at the respective stimulation frequency and preceding baseline. No significant differences were detected between right and left vagal nerve stimulation (VNS).

Mentions: As the stimulation frequency was increased from 2 Hz to 5 Hz, 10 Hz, and 20 Hz, heart rate progressively decreased at both tested pulse durations (0.1 msec and 1.0 msec) (Fig. 3). This bradycardic response was similar for left‐ and right‐sided vagal nerve stimulation, although at a pulse duration of 1.0 msec, the lowest stimulation frequency tested (2 Hz) caused a significant bradycardia only for left‐sided vagal nerve stimulation. Increasing the stimulation frequency did not have a significant effect on mean arterial blood pressure except a small hypotensive response at the combination of 3 V, 0.1 msec, and 20 Hz for right‐sided vagal nerve stimulation. At the shorter pulse duration (0.1 msec), respiration rate increased as the stimulation frequency was increased. However, at the longer pulse duration (1.0 msec), even at the lowest stimulation frequency tested (2 Hz) a marked and significant increase in respiration rate was observed. Increasing the stimulation frequency above 2 Hz reduced this tachypneic effect observed at a pulse duration of 1.0 msec. No statistically significant differences in the respiratory responses were observed between right‐and left‐sided vagal nerve stimulation.


Differential hemodynamic and respiratory responses to right and left cervical vagal nerve stimulation in rats
Changes (Δ) in heart rate (HR0, mean arterial blood pressure (MAP), and respiratory frequency (RF) in response to left‐ (closed circles, n = 3) or right‐sided (open circles, n = 4) cervical vagal nerve stimulation using increasing stimulation frequencies (x‐axes) of charge balanced rectangular impulses of 3 V and pulse durations of 0.1 msec (left) or 1.0 msec (right). Absolute baseline values are provided in Table 2. *: P < 0.05 for difference of absolute values at the respective stimulation frequency and preceding baseline. No significant differences were detected between right and left vagal nerve stimulation (VNS).
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phy213244-fig-0003: Changes (Δ) in heart rate (HR0, mean arterial blood pressure (MAP), and respiratory frequency (RF) in response to left‐ (closed circles, n = 3) or right‐sided (open circles, n = 4) cervical vagal nerve stimulation using increasing stimulation frequencies (x‐axes) of charge balanced rectangular impulses of 3 V and pulse durations of 0.1 msec (left) or 1.0 msec (right). Absolute baseline values are provided in Table 2. *: P < 0.05 for difference of absolute values at the respective stimulation frequency and preceding baseline. No significant differences were detected between right and left vagal nerve stimulation (VNS).
Mentions: As the stimulation frequency was increased from 2 Hz to 5 Hz, 10 Hz, and 20 Hz, heart rate progressively decreased at both tested pulse durations (0.1 msec and 1.0 msec) (Fig. 3). This bradycardic response was similar for left‐ and right‐sided vagal nerve stimulation, although at a pulse duration of 1.0 msec, the lowest stimulation frequency tested (2 Hz) caused a significant bradycardia only for left‐sided vagal nerve stimulation. Increasing the stimulation frequency did not have a significant effect on mean arterial blood pressure except a small hypotensive response at the combination of 3 V, 0.1 msec, and 20 Hz for right‐sided vagal nerve stimulation. At the shorter pulse duration (0.1 msec), respiration rate increased as the stimulation frequency was increased. However, at the longer pulse duration (1.0 msec), even at the lowest stimulation frequency tested (2 Hz) a marked and significant increase in respiration rate was observed. Increasing the stimulation frequency above 2 Hz reduced this tachypneic effect observed at a pulse duration of 1.0 msec. No statistically significant differences in the respiratory responses were observed between right‐and left‐sided vagal nerve stimulation.

View Article: PubMed Central - PubMed

ABSTRACT

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&#8208; or left&#8208;sided cervical VNS in a hypertensive rat model. Anesthetized stroke&#8208;prone spontaneously hypertensive rats were instrumented for arterial blood pressure and heart rate monitoring and left&#8208; or right&#8208;sided VNS. Cervical VNS was applied through bipolar coil electrodes. Stimulation parameters tested were 3&nbsp;V and 6&nbsp;V, 2&nbsp;Hz to 20&nbsp;Hz stimulation frequency, and 50&nbsp;&mu;sec to 20&nbsp;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&#8208;sided than with right&#8208;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 (&lt;5&nbsp;Hz) and short pulse durations (&lt;0.5&nbsp;msec) primarily larger A&#8208;fibers are activated, while at longer pulse durations (&gt;0.5&nbsp;msec) smaller B&#8208;fibers are also recruited. In conclusion, in rats left&#8208;sided cervical VNS causes greater cardio&#8208;respiratory responses than right&#8208;sided VNS and at lower stimulation frequencies (e.g., 5&nbsp;Hz), longer pulse durations (&gt;0.5&nbsp;msec) seem to be required to consistently recruit B&#8208;fibers in addition to A&#8208;fibers.

No MeSH data available.