Use of hdac inhibitors for treatment of cardiac rhythm disorders

Abstract

The present invention provides methods of ameliorating or reducing the extent of cardiac arrhythmia disorders, by administering an inhibitor of histone deacetylase enzyme (HDAC).

What is claimed is: 
     
         1 . A method of treating a cardiac rhythm disorder in a subject, comprising administering to said subject an inhibitor of a histone deacetylase (HDAC), thereby treating a cardiac rhythm disorder in a subject. 
     
     
         2 . The method of  claim 1 , wherein said cardiac rhythm disorder comprises an irregular cardiac rhythm. 
     
     
         3 . The method of  claim 1 , wherein said cardiac rhythm disorder comprises a rapid cardiac rhythm. 
     
     
         4 . The method of  claim 1 , wherein said cardiac rhythm disorder comprises a chaotic cardiac rhythm. 
     
     
         5 . The method of  claim 1 , wherein said cardiac rhythm disorder is a chronic cardiac rhythm disorder. 
     
     
         6 . The method of  claim 1 , wherein said subject is further affected with a ventricular hypertrophy disorder. 
     
     
         7 . The method of  claim 1 , wherein said subject is further affected with a diastolic dysfunction. 
     
     
         8 . The method of  claim 1 , wherein said cardiac rhythm disorder is an atrial fibrillation disorder. 
     
     
         9 . The method of  claim 1 , wherein said inhibitor of an HDAC is trichostatin A. 
     
     
         10 . The method of  claim 1 , wherein said inhibitor of an HDAC is selected from: a valproic acid, a suberoylanilide hydroxamic acid (SAHA), an epoxyketone-containing cyclic tetrapeptide, a non-epoxyketone-containing cyclic tetrapeptide, a benzamine, depudecin, or any mixture thereof. 
     
     
         11 . The method of  claim 1 , wherein the step of treating a cardiac rhythm disorder in said subject, comprises restoring atrial connexin distribution in said subject. 
     
     
         12 . The method of  claim 1 , wherein the step of treating a cardiac rhythm disorder in said subject, comprises reducing atrial collagen content in said subject. 
     
     
         13 . A method of reducing the incidence of a cardiac rhythm disorder in a subject, comprising administering to said subject an inhibitor of a histone deacetylase (HDAC), thereby reducing said incidence of a cardiac rhythm disorder in a subject. 
     
     
         14 . The method of  claim 13 , wherein said cardiac rhythm disorder comprises an irregular cardiac rhythm. 
     
     
         15 . The method of  claim 13 , wherein said cardiac rhythm disorder comprises a rapid cardiac rhythm. 
     
     
         16 . The method of  claim 12 , wherein said cardiac rhythm disorder comprises a chaotic cardiac rhythm. 
     
     
         17 . The method of  claim 13 , wherein said cardiac rhythm disorder is a chronic cardiac rhythm disorder. 
     
     
         18 . The method of  claim 13 , wherein said subject is affected with a ventricular hypertrophy disorder. 
     
     
         19 . The method of  claim 13 , wherein said subject is affected with a diastolic dysfunction. 
     
     
         20 . The method of  claim 13 , wherein said cardiac rhythm disorder is an atrial fibrillation disorder. 
     
     
         21 . The method of  claim 13 , wherein said inhibitor of an HDAC is trichostatin A. 
     
     
         22 . The method of  claim 13 , wherein said inhibitor of an HDAC is selected from: a valproic acid, a suberoylanilide hydroxamic acid (SAHA), an epoxyketone-containing cyclic tetrapeptide, a non-epoxyketone-containing cyclic tetrapeptide, a benzamine, depudecin, or any mixture thereof. 
     
     
         23 . The method of  claim 13 , wherein said method comprises the step of comprises reducing the incidence of atrial arrhythmogenesis in said subject. 
     
     
         24 . The method of  claim 13 , wherein said method comprises the step of reducing atrial collagen content in said subject. 
     
     
         25 . The method of  claim 13 , said method comprises the step of restoring atrial connexin distribution in said subject. 
     
     
         26 . A method of reducing atrial collagen content in a subject, comprising administering to said subject an inhibitor of a histone deacetylase (HDAC), thereby reducing said atrial collagen content in a subject. 
     
     
         27 . The method of  claim 26 , wherein said subject is affected with a ventricular hypertrophy disorder. 
     
     
         28 . The method of  claim 26 , wherein said subject is affected with a diastolic dysfunction. 
     
     
         29 . The method of  claim 26 , wherein said inhibitor of an HDAC is trichostatin A. 
     
     
         30 . The method of  claim 26 , wherein said inhibitor of an HDAC is selected from: a valproic acid, a suberoylanilide hydroxamic acid (SAHA), an epoxyketone-containing cyclic tetrapeptide, a non-epoxyketone-containing cyclic tetrapeptide, a benzamine, depudecin, or any mixture thereof. 
     
     
         31 . A method of restoring an atrial connexin distribution in a subject, comprising administering to said subject an inhibitor of a histone deacetylase (HDAC), thereby restoring an atrial connexin distribution in a subject. 
     
     
         32 . The method of  claim 31 , wherein said subject is affected with a ventricular hypertrophy disorder. 
     
     
         33 . The method of  claim 31 , wherein said subject is affected with a diastolic dysfunction. 
     
     
         34 . The method of  claim 31 , wherein said inhibitor of an HDAC is trichostatin A. 
     
     
         35 . The method of  claim 31 , wherein said inhibitor of an HDAC is selected from: a valproic acid, a suberoylanilide hydroxamic acid (SAHA), an epoxyketone-containing cyclic tetrapeptide, a non-epoxyketone-containing cyclic tetrapeptide, a benzamine, depudecin, or any mixture thereof. 
     
     
         36 . A method of reducing the incidence of atrial arrhythmogenesis in a subject, comprising administering to said subject an inhibitor of a histone deacetylase (HDAC), thereby reducing the incidence of atrial arrhythmogenesis in a subject. 
     
     
         37 . The method of  claim 36 , wherein said subject is further affected with a ventricular hypertrophy disorder. 
     
     
         38 . The method of  claim 36 , wherein said subject is further affected with a diastolic dysfunction. 
     
     
         39 . The method of  claim 36 , wherein said inhibitor of an HDAC is trichostatin A. 
     
     
         40 . The method of  claim 36 , wherein said inhibitor of an HDAC is selected from: a valproic acid, a suberoylanilide hydroxamic acid (SAHA), an epoxyketone-containing cyclic tetrapeptide, a non-epoxyketone-containing cyclic tetrapeptide, a benzamine, depudecin, or any mixture thereof. 
     
     
         41 . The method of  claim 36 , wherein said method comprises the step of restoring atrial connexin distribution in said subject. 
     
     
         42 . The method of  claim 36 , wherein said method comprises the step of reducing atrial collagen content in said subject.