Cardiac arrhythmia treatment methods

Abstract

Disclosed are methods of preventing or treating cardiac arrhythmia. In one embodiment, the methods include administering to an amount of at least one polynucleotide that modulates an electrical property of the heart. The methods have a wide variety of important uses including treating cardiac arrhythmia.

1 . A method of preventing or treating cardiac arrhythmia comprising administering to a mammal a therapeutically effective amount of at least one polynucleotide capable of modulating an electrical property in a standard cardiac electrophysiological assay; and expressing the polynucleotide in the mammal to prevent or treat the cardiac arrhythmia.  
     
     
         2 - 11 . (canceled)  
     
     
         12 . The method of  claim 1 , wherein the polynucleotide encodes a K channel subunit, Na channel subunit, Ca channel subunit, an inhibitory G protein subunit, a connexin; or a functional fragment thereof.  
     
     
         13 . The method of  claim 12 , wherein the method further comprises overexpressing the K channel protein subunit sufficient to decrease cardiac action potential duration (APD) by at least about 5% as determined by the assay.  
     
     
         14 . The method of  claim 13 , wherein overexpression of the K channel protein subunit is further sufficient to decrease surface electrocardiogram (ECG) repolarization time by at least about 5% as determined by the assay.  
     
     
         15 . The method of  claim 13  or  14 , wherein the K channel protein subunit is overexpressed by at least about 2 fold relative to endogenous K channel protein as determined by a standard Western blot assay.  
     
     
         16 . The method of  claim 13  or  14  wherein the K channel protein subunit is overexpressed and impacts repolarization in congestive heart failure or myocardial infarction in the long QT syndrome.  
     
     
         17 - 20 . (canceled)  
     
     
         21 . The method of  claim 12 , wherein the inhibitory G protein subunit is Gα i2  or a functional fragment thereof.  
     
     
         22 .- 26 . (canceled)  
     
     
         27 . A method of preventing or treating ventricular rate or pulse during atrial fibrillation comprising administering to a mammal a therapeutically effective amount of at least one polynucleotide encoding a Gα i2  or a functional fragment thereof; and expressing the polynucleotide in the mammal to prevent or treat the atrial fibrillation.  
     
     
         28 . The method of  claim 27 , wherein the method further comprises overexpressing the Gα i2  or a functional fragment thereof sufficient to decrease speed of conduction through the atrioventricular (AV) node (A-H interval) or His-Purkinje system as determined by a standard electrophysiological assay.  
     
     
         29 . The method of  claim 28 , wherein the decrease in the A-H interval is accompanied by a decrease in AV node refractory period (AVNERP).  
     
     
         30 . The method of  claim 28  or  29 , wherein the decrease in the A-H interval is at least about 10% as determined by the assay.  
     
     
         31 . The method of  claim 29 , wherein the increase in AVNERP is at least about 10% relative as determined by the assay.  
     
     
         32 . The method of  claim 27 , wherein overexpression of the Gα i2  or a functional fragment thereof is capable of decreasing pulse rate or ventricular rate during atrial fibrillation as determined by a standard cardiac electrophysiological assay.  
     
     
         33 . The method of  claim 32 , wherein the decrease in pulse rate or ventricular rate during atrial fibrillation is at least about 10% as determined by the assay.  
     
     
         34 . The method of  claim 27 , wherein the polynucleotide encoding the Gα i2  subunit hybridizes to the nucleic acid sequence shown in SEQ ID No. 1; or the complement thereof under high stringency hybridization conditions.  
     
     
         35 . The method of  claim 34 , wherein the polynucleotide comprises the nucleic acid shown in SEQ ID NO. 1 ( FIG. 9 ); or a functional fragment of that sequence.  
     
     
         36 - 55 . (canceled)  
     
     
         56 . The method of  claim 1  wherein heart rate is increased by at least about 5% relative to baseline by the creation of a biological pacemaker.  
     
     
         57 . The method of any of claims  1  and  56 , wherein the biological pacemaker is induced by administration of a polynucleotide designed to suppress K channels.  
     
     
         58 . The method of  claim 57 , wherein the K channel suppressed by administration of a polynucleotide is the inward rectifier K channel, a.k.a. I Kl .  
     
     
         59 . The method of  claim 58 , wherein the polynucleotide is a dominant-negative construct of Kir2.1.