Project: Research project

Project Details


Recent studies suggest that antiarrhythmic drugs (AADs) may protect against
potentially lethal ventricular arrhythmias independent of quantitative
suppression of chronic ventricular ectopic activity (VEA); i.e.; a
dissociation between "antifibrillatory/antitachycardia" and
"antidyrhythmic" drug actions. In addition, there are conflicting data on
the best end-points for antiarrhythmic management of patients at risk for
potentially lethal arrhythmias. Therefore, this project was designed for
the ultimate goal of developing better guiding principles for the use of
AADs. The studies are based on the premise that fundamental information on
relationships between forms of VEA, clinical settings in which they occur,
and responses of ventricular arrhythmias to therapy, must be accumulated
and analyzed before the ultimate aim can be achieved. Three major
hypotheses will be tested: (1) that concentration-response relationships
between AADs and potentially lethal arrhythmias differ from those for
various forms of non-lethal VEA; (2) that antiarrhythmic effectiveness
varies as a function of clinical setting in which a specific arrhythmia
occurs; and (3) that concentration-response relationships vary as a
function of free drug concentrations. The hypotheses will be tested in 4
patient categories, based on our preliminary data: (1) patients who have
chronic VEA of different forms; (2) patients with acute myocardial
infarction with VEA studied longitudinally - acutely, during convalescence,
about 3 weeks after the acute event; (3) patients who have recurrent
sustained ventricular tachycardia (VT) and a background of chronic VEA; and
(4) survivors of prehospital cardiac arrest. In patients without
life-threatening arrhythmias, the relationship between free and total
plasma concentrations of AADs on forms and frequencies of ventricular
arrhythmias will be studied. Three standard drugs with different binding
kinetics will be used: the highly bound drug quinidine; the poorly bound
drug procainamide; and a drug with concentration-related binding,
disopyramide. In patients with life-threatening arrhythmias, 3 end-points
of therapy will be evaluated: (1) concentration-related changes in
frequencies or forms of chronic VEA; (2) changes in inducibility of VT, and
simultaneous changes in VEA, during drug testing in the electrophysiology
laboratory; and (3) the influence of free and total plasma levels of AADs
on long-term arrhythmia control. Clarification of the relationships
between forms of arrhythmias, clinical settings, and responses measured in
terms of various end-points of therapy will provide fundamental information
needed to define the role of AADs in patients who have potentially lethal
or non-lethal forms of ventricular arrhythmias.
Effective start/end date7/1/906/30/92


  • National Heart, Lung, and Blood Institute


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