Insular cortex stimulation produces lethal cardiac arrhythmias: a mechanism of sudden death?

doi:10.1016/0006-8993(91)90412-O

Brain Research

Volume 550, Issue 1, 31 May 1991, Pages 115-121

https://doi.org/10.1016/0006-8993(91)90412-O Get rights and content

Abstract

The rat posterior insular cortex has recently been shown to possess cardiac chronotropic organization and therefore may be involved in cortical mechanisms of sudden death. In order to assess the potential of this region for cardiac arrhythmogenicity, phasic microstimulation of tachycardia zones undertaken in the urethane-anesthetized rat. The insular stimulus was triggered by the R wave of the electrocardiogram (ECG) and delayed so that resultant putative cardiac sympathetic nerve activity would be synchronous with the T wave of the ECG. This resulted in increasing degrees of heart block leading to escape rhythms, ventricular ectopics and ultimately death in asystole. Heart block was associated with elevated plasma norepinephrine levels and myocardial damage. Such effects have not been previously demonstrated for a cortical site. These data suggest that pathophysiological activation of the insular cortex by stroke, epileptic seizure, or under conditions of severe emotional stress could predispose to ECG changes, cardiac arrhythmias and sudden death.

Reference (43)

CechettoD.F. et al.
Autonomic and myocardial changes in middle cerebral artery stroke models in the rat
Brain Research
(1989)
IwataJ. et al.
Cardiovascular responses elicited by stimulation of neurons in the central amygdaloid nucleus in awake but not anesthetized rats resemble conditioned emotional responses
Brain Research
(1987)
LepeschkinE. et al.
Effect of epinephrine and norepinephrine on the electrocardiogram of 100 normal subjects
Am. J. Cardiol.
(1960)
MelvilleK.I. et al.
Cardiac responses to epinephrine and norepinephrine during prolonged cholesterol and high fat feeding in rabbits
Am. J. Cardiol.
(1959)
MicalizziE.R. et al.
Evaluation of plasma norepinephrine as an index of sympathetic neuron function in the conscious unrestrained rat
Life Sci.
(1979)
OppenheimerS.M. et al.
The cardiac chronotropic organisation of the rat insular cortex
Brain Research
(1990)
SmithK.E. et al.
Changes in plasma catecholamine levels after insula damage in experimental stroke
Brain Research
(1986)
AngelakosE.T. et al.
Regional distribution of catecholamines in the hearts of different species
Ann. N.Y. Acad. Sci.
(1969)
BlumhardtL.D. et al.
Electrocardiographic accompanyments of temporal lobe epileptic seizures
Lancet
(1986)
CechettoD.F. et al.
Subcortical sites mediating sympathetic responses from insular cortex in rats
Am. J. Physiol.
(1990)

CechettoD.F. et al.

Role of the cerebral cortex in autonomic function

CechettoD.F. et al.

Effect of age on cardiac and autonomic responses in the rat stroke model

Stroke

(1990)

ConnorR.

Heart damage associated with intracranial lesions

Br. Med. J.

(1968)

DelgadoJ.M.R.

Circulatory effects of cortical stimulation

Physiol. Rev.

(1960)

EganT.E. et al.

An isoprenaline activated sodium-dependent inward current in ventricular myocytes

Nature

(1987)

GoldsteinD.S.

The electrocardiogram in stroke: relationship to pathophysiological type and comparison with prior tracings

Stroke

(1979)

GreenbergH.M.

Bradycardia at onset of sudden death: potential mechanisms

Ann. N.Y. Acad. Sci.

(1984)

GreenhootJ.H. et al.

Cardiac injury and subarachnoid hemorrhage, a clinical, pathological, and physiological correlation

J. Neurosurg.

(1969)

KolinA. et al.

Pseudoinfarction pattern of the QRS complex in experimental cardiac hypoxia induced by noradrenalin

Cardiologia

(1963)

KortewegG.C.J. et al.

Influence of stimulation of some subcortical areas on electrocardiogram

J. Neurophysiol.

(1957)

KoskeloP. et al.

Subendocardial haemorrhage and ECG changes in intracranial bleeding

Br. Med. J.

(1964)

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To explore the first possibility, we used electrical stimulation to create a model of focal epilepsy in the insular cortexes of rats, in which we specifically targeted the granular cell layer which controls the heart and respiratory rates. In contrast to existing widely used genetic [5,31,35] and traditional acute insular cortex kindling models [11,24], we have provide a chronic and more clinically similar model that will enable long-term studies of the role of the insular cortex in SUDEP. During our kindling procedure, stimulation of the granular cell layer of the insular cortex was intended to induce AD, an epileptiform activity.
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Insular cortex stimulation produces lethal cardiac arrhythmias: a mechanism of sudden death?

Abstract

Brain Research

Brain Research

Am. J. Cardiol.

Am. J. Cardiol.

Life Sci.

Brain Research

Brain Research

Regional distribution of catecholamines in the hearts of different species

Ann. N.Y. Acad. Sci.

Electrocardiographic accompanyments of temporal lobe epileptic seizures

Lancet

Subcortical sites mediating sympathetic responses from insular cortex in rats

Am. J. Physiol.

Role of the cerebral cortex in autonomic function

Effect of age on cardiac and autonomic responses in the rat stroke model

Stroke

Heart damage associated with intracranial lesions

Br. Med. J.

Circulatory effects of cortical stimulation

Physiol. Rev.

An isoprenaline activated sodium-dependent inward current in ventricular myocytes

Nature

The electrocardiogram in stroke: relationship to pathophysiological type and comparison with prior tracings

Stroke

Bradycardia at onset of sudden death: potential mechanisms

Ann. N.Y. Acad. Sci.

Cardiac injury and subarachnoid hemorrhage, a clinical, pathological, and physiological correlation

J. Neurosurg.

Pseudoinfarction pattern of the QRS complex in experimental cardiac hypoxia induced by noradrenalin

Cardiologia

Influence of stimulation of some subcortical areas on electrocardiogram

J. Neurophysiol.

Subendocardial haemorrhage and ECG changes in intracranial bleeding

Br. Med. J.