Sympathetic mechanisms in an animal model of vasovagal syncope.

Abstract

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. Left thoracotomy was performed on 20 mongrel dogs. The heart was exposed and a bolus of veratridine (15μg/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 30s before and 30s after veratridine injection. 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±33.81ng/l, p=0.002) and less intense drops in heart rate (-37±24 vs. -84±28bpm, p=0.001) and blood pressure (systolic blood pressure, -18±15 vs. -37±13mmHg, p=0.009; diastolic blood pressure, -26±13 vs. -45±13mmHg, p=0.005) compared to dogs in Group B. Similarly, heart rate post-veratridine was higher (102±23 vs. 69±22bpm, 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. 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.