Autonomic consequences of kainic acid-induced limbic cortical seizures in rats: Peripheral autonomic nerve activity, acute cardiovascular changes, and death

Authors: Sakamoto, Kenichi¹; Saito, Takeshi¹; Orman, Rena¹; Koizumi, Kiyomi¹; Lazar, Jason²; Salciccioli, Louis²; Stewart, Mark

Source: Epilepsia, Volume 49, Number 6, June 2008 , pp. 982-996(15)

Publisher: Wiley-Blackwell

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Abstract:

Summary

Purpose: Autonomic consequences of seizures are common, but can be severe. We sought to define changes in autonomic activity from limbic cortical seizures and their impact on the heart.

Methods: We studied kainic acid (KA)-induced seizures in urethane-anesthetized rats using peripheral nerve, blood pressure (BP), and ECG recordings and echocardiography.

Results: Seizures were associated with massive increases in parasympathetic (vagus nerves) and sympathetic (cervical sympathetic ganglion >renal nerve >splanchnic nerve) activity. Seizure-associated activity increases were greater than activity changes induced by nitroprusside or phenylephrine (each producing BP changes of >50 mmHg). Increases in c-fos expression were found in both sympathetic and parasympathetic medullary regions (as well as hypothalamic areas). Baroreceptor reflex function (tested with nitroprusside and phenylephrine) was impaired during seizures. Finally, a significant fraction of the animals died and the mechanism of death was defined through ECG, BP, and echocardiographic measures to be profound cardiac dilatation and bradyarrhythmia leading to hypoperfusion of the brain and ultimately hypoperfusion of the heart. Cardiovascular changes occur within seconds (or less) of autonomic nerve activity changes and death by these mechanisms takes minutes.

Discussion: We propose that the massive parasympathetic and sympathetic outflow that occurs during a seizure gets compounded by respiratory distress (driving both autonomic nervous system divisions in the same direction) causing mechanical dysfunction, slowing the heart, and hypoperfusing the brain.

Keywords: Autonomic nervous system; Limbic cortex; Cardiac arrhythmia; Cardiac dilatation

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1528-1167.2008.01545.x

Affiliations: 1: Departments of Physiology & Pharmacology 2: Medicine, Division of Cardiovascular Medicine

Publication date: 2008-06-01

Autonomic consequences of kainic acid-induced limbic cortical seizures in rats: Peripheral autonomic nerve activity, acute cardiovascular changes, and death

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