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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Neurobehavioral contributions to cardiac arrhythmias during aversive pavlovian conditioning in the rabbit receiving digitalis.

Clinical observations suggest that a prevalent condition for the occurrence of cardiac arrhythmias is the synergistic interaction of several risk factors including digitalis glycosides, myocardial ischemia and psychological stress. However, little research has been directed toward controlled, systematic investigations of such synergistic interaction, particularly with respect to psychological stress and digitalis glycosides. The present research was undertaken to develop an animal model with which to study the behavioral and neurobiological contributions to arrhythmias during psychological stress in the presence of digitalis. The model used the rabbit as the experimental animal, a pavlovian aversive conditioning procedure and ouabain, a digitalis glycoside. Rabbits received pavlovian conditioning trials in which a tone as a conditioned stimulus (CS) was paired with an eyelid shock as an unconditioned stimulus (US). Twenty-four hours later, a retention test was given in which either of two doses of ouabain or saline was given, followed by 20 CS presentations alone. The CS presentations were given every 120 s (+/- 10 s). During ouabain infusion, the CS significantly increased the frequency of arrhythmic episodes compared to pre-CS baseline frequencies. These arrhythmic episodes were invariably preceded by CS-induced bradycardia. Both parasympathetic and sympathetic involvement were suggested in arrhythmogenesis, since the CS-induced increase in arrhythmic episodes was blocked by pretreatment with either atropine methylnitrate or atenolol. Furthermore, electrical stimulation of the amygdaloid central nucleus, an area implicated in the expression of bradycardia to a pavlovian CS in the rabbit produced arrhythmic episodes in the presence of ouabain. These arrhythmic episodes were similar in topography to CS-induced arrhythmias within any one animal and were decreased by atropine methylnitrate pretreatment. Insights into central and peripheral nervous system mechanisms by which psychological stress is capable of evoking cardiac arrhythmias in the presence of ouabain should ultimately lead to more effective treatment strategies for the prevention of these arrhythmias.[1]

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