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Autonomic and pharmacologic modulation of the frequency-dependent properties of the atrioventricular node

By Mohsen Nayebpour

Abstract

The responses of the atrioventricular node (AVN) to changes in activation rate is complex. A variety of approaches have been used to explain the different responds of AVN, but none has been able to describe fully nodal behavior. Three rate-dependent nodal properties referred to as recovery, facilitation, and fatigue contribute to rate-induced changes in nodal conduction time. We developed a model incorporating a quantitative description of these properties that was able to accurately predict AV node conduction during steady state atrial pacing. This model provides a mathematical framework through which interventions such as changes in the autonomic tone may affect AV nodal conduction. This was evaluated by studying effects of vagal stimulation (VS), isoproterenol (IP), and beta blockade (BB) an AVN conduction. Experimental results and mathematical modelling revealed that these interventions alter the ways in which the AVN responds to changes in activation rate. These changes result in enhanced rate-dependent AVN conduction slowing with VS and BB, and reduced rate-dependent slowing with IP.The potential implications of the rate-dependent properties of the AVN were studied by evaluating whether the depressant effects of diltiazem (D) on the AVN are enhanced during arrhythmias which increase AVN activation rate. The relative magnitude of D's effects on the AVN during tachycardia (atrial fibrillation, and circus movement tachycardia) were significantly magnified compared to the effects at races comparable to sinus rhythm in man. Rate-dependent calcium channel-blocking properties of D were an intrinsic property, though their intensity was modulated by autonomic tone. This thesis provides a link between basic theories of rate dependent properties and physiologic and pharmacologic implications

Topics: Health Sciences, Pharmacology.
Publisher: McGill University
Year: 1991
OAI identifier: oai:digitool.library.mcgill.ca:74605
Provided by: eScholarship@McGill
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