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Sympathetic mechanisms in an animal model of vasovagal syncope

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Abstract

Purpose

Individuals predisposed to vasovagal syncope may have different autonomic nervous system control mechanisms from those without predisposition to vasovagal events. To test this hypothesis, we investigated different sympathetic responses in a canine model of vasovagal syncope.

Methods

Left thoracotomy was performed on 20 mongrel dogs. The heart was exposed and a bolus of veratridine (15 μg/kg), a neurotoxin which prevents the inactivation of sodium ion channels, was injected into the left atrium to induce a Bezold–Jarisch reflex-mediated vasovagal event, characterized by bradycardia, decreased inotropism, and hypotension. Electrocardiogram and blood pressure were continuously monitored. Neural activity was recorded from the left stellate ganglion. Plasma norepinephrine and acetylcholine levels were measured 30 s before and 30 s after veratridine injection.

Results

Veratridine resulted in rapid decreases in heart rate and blood pressure in all dogs, accompanied by increases in both norepinephrine and acetylcholine. Two types of neural activity (high-amplitude spike discharge activity and low-amplitude burst discharge activity) were recorded from the left stellate ganglion. Veratridine induced high-frequency spike discharge activity in some dogs (Group A), whereas spike discharge activity was scarce and relatively unresponsive to veratridine in the remaining dogs (Group B). Dogs in Group A had higher plasma norepinephrine levels (111.63 ± 15.1 vs. 48.11 ± 33.81 ng/l, p = 0.002) and less intense drops in heart rate (− 37 ± 24 vs. − 84 ± 28 bpm, p = 0.001) and blood pressure (systolic blood pressure, − 18 ± 15 vs. − 37 ± 13 mmHg, p = 0.009; diastolic blood pressure, − 26 ± 13 vs. − 45 ± 13 mmHg, p = 0.005) compared to dogs in Group B. Similarly, heart rate post-veratridine was higher (102 ± 23 vs. 69 ± 22 bpm, p = 0.004), the veratridine-induced longest RR interval was shorter (0.7 [0.5–0.8] vs. 1.2 [1.1–3.5] s, p < 0.001) and the diastolic and mean arterial pressures post-veratridine were higher (all p < 0.05) in dogs in Group A compared to those in Group B.

Conclusions

Distinct sympathetic activation as represented by left stellate ganglion high-frequency spike discharge activity protected against bradycardia and hypotension in a canine model of vasovagal syncope. Our findings may have therapeutic implications.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Numbers 81400254, 81370281, 81530011), and the Natural Science Foundation of Hubei Province (Grant Number 2015CFA051).

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Correspondence to Hong Jiang.

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The authors declare that they have no conflict of interest.

Human and animal rights

All animal studies were approved by the animal experimental administration of Wuhan University and the ethics committee of Wuhan University Renmin Hospital. The investigation conforms to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 8023, revised 1978). The manuscript does not contain clinical studies or patient data.

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He, W., Wang, X., Liu, S. et al. Sympathetic mechanisms in an animal model of vasovagal syncope. Clin Auton Res 28, 333–340 (2018). https://doi.org/10.1007/s10286-018-0503-5

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