Use of autonomic nervous system neurotransmitters inhibition and atrial parasympathetic fibers ablation for the treatment of atrial arrhythmias and to preserve drug effects

Abstract

Atrial arrhythmias, a major contributor to cardiovascular morbidity, are believed to be influenced by autonomic nervous system tone. The main purpose of this invention was to highlight new findings that have emerged in the study of effects of autonomic nervous system tone on atrial arrhythmias, and its interaction with class III antiarrhythmic drug effects. This invention evaluates the significance of sympathetic and parasympathetic activation by determining the effects of autonomic nervous system using a vagal and stellar ganglions stimulation, and by using autonomic nervous system neurotransmitters infusion (norepinephrine, acetylcholine). This invention evaluates the autonomic nervous system effects on the atrial effective refractory period duration and dispersion, atrial conduction velocity, atrial wavelength duration, excitable gap duration during a stable circuit (such atrial flutter circuit around an anatomical obstacle), and on the susceptibility of occurrence (initiation, maintenance and termination) of atrial re-entrant arrhythmias in canine. This invention also evaluates whether autonomic nervous system activation effects via a local neurotransimitters infusion into the right atria can alter those of class III antiarrhythmic drug, sotalol, during a sustained right atrial flutter. This invention represents an emergent need to set-up and develop a new class of anti-cholinergic drug therapy for the treatment of atrial arrhythmias and to combine this new anti-cholinergic class to antiarrhythmic drugs. Furthermore, this invention also highlights the importance of a local application of parasympathetic neurotransmitters/blockers and a catheter ablation of the area of right atrium with the highest density of parasympathetic fibers innervation. This may significantly reduce the occurrence of atrial arrhythmias and may preserve the antiarrhythmic effects of any drugs used for the treatment of atrial re-entrant arrhythmias.

1. A method comprising the step of inhibiting the effects of the parasympathetic nervous system neurotransmitter release on the atria, wherein said method converting and prevents atrial flutter and fibrillation. 
     
     
       2. A method for significantly increasing conversion of sustained atrial flutter to non-sustained atrial fibrillation, the method comprising the step of locally infusing the a parasympathetic neurotransmitter, wherein said method significantly increases the conversion of sustained atrial flutter to non sustained atrial fibrillation on a portion of the atria via a catheter. 
     
     
       3. A method for significantly reversing antiarrhythmic effects of a class 3 antiarrhythmic drug, the method comprising the step of local locally infusing the a parasympathetic neurotransmitter on a portion of the atria via a catheter during a sustained atrial flutter, wherein said method significantly reverses the antiarrhythmic effects of a class 3 antiarrhythmic drug, sotalol. 
     
     
       4. The method, according to anyone of claims claim  2  or  3 , wherein further comprising the step of infusing a parasympathetic nervous system blocker via the catheter to significantly preserves preserve the antiarrhythmic effects of a class 3 antiarrhythmic drugs drug on the occurrence of a sustained atrial re-entrant arrhythmias arrhythmia. 
     
     
       5. The method, according to anyone any one of  claims 2  or  3 , wherein further comprising infusing a parasympathetic nervous system blocker via the catheter to significantly preserves preserve the antiarrhythmic effects of class I, II, IV, V, or any other drugs used for the treatment of any of atrial re-entrant arrhythmias arrhythmia. 
     
     
       6. A method of treating atrial fibrillation and flutter, wherein delivering an anticholinergic agent to the myocardium significantly converts and prevents the occurrence of atrial flutter and fibrillation comprising at least one of:
 a) infusing drug via the coronary arteries,   b) a direct application via drug eluting patch on the atrial epicardium,   c) a direct application via drug eluting catheter on the atrial endocardium.   
     
     
       7. A method, wherein catheter ablation of the atria in areas with the greatest density of parasympathetic nerve innervation significantly converts and prevents the occurrence of atrial fibrillation and flutter or other re-entrant atrial arrhythmias comprising:
 inserting an electrophysiologic ablation catheter having a tip section with an ablation electrode into the right or left atrial chambers and directing the catheter to endomyocardial locations with high density of the parasympathetic fibers;   stabilizing the ablation electrode at said myocardium location;   delivering effective ablation energy through the electrode sufficient to destroy the parasympathetic nerve fibers in order to eliminate their neurotransmitter effects in the atria.   
     
     
       8. The method, according to  claim 3  or  7 , wherein catheter ablation of the atria in areas with the greatest density of parasympathetic nerve innervation significantly preserves and enhances the antiarrhythmic effects of any drugs used for the treatment of atrial arrhythmias. 
     
     
       9. The method according to claim 3 further comprising the step of infusing a parasympathetic nervous system blocker via the catheter to significantly preserve the antiarrhythmic effects of a class 3 antiarrhythmic drug on the occurrence of a sustained atrial re-entrant arrhythmia.