Treatment of cardiac arrhythmias

Abstract

Compositions of the invention, including compounds that bind to a receptor for a glucagon-like peptide-1, an incretin, a glucagon-like peptide-1 (GLP-1), an exendin, or an agonist, an analog (preferably an agonist analog), a derivative, or a variant of any of aforementioned compounds, are used in the prevention and treatment of arrhythmias associated with cardiac ischemia, cardiac ischemia-perfusion and/or congestive heart failure. The invention relates to both the method and compositions for such treatment.

We claim: 
     
         1 . A method for treating arrhythmias, the method comprising:
 administering to a subject in need of such treatment an amount of a composition effective to treat arrhythmias, said composition comprising a polypeptide of Formula VII (SEQ ID NO:29) or VIII (SEQ ID NO:30) that binds to a receptor for GLP-1; and thereby treating said arrhythmias, wherein   Xaa 1  is 4-imidazopropionyl;   Xaa 21  is Lys-NH ε -R where R is Lys, Arg, C 1 -C 10  straight chain or branched chain alkanoyl or cycloalkylalkanoyl; and   X 1  is Lys Asn, Asn Lys, Lys-NH ε -R Asn, Asn Lys-NH ε -R, Lys-NH ε -R Ala, Ala Lys-NH ε -R where R is Lys, Arg, C 1 -C 10  straight chain or branched chain alkanoyl or cycloalkylalkanoyl.   
     
     
         2 . The method of  claim 1  wherein the composition is administered in a dose of from about 0.1 pmol/kg/min. up to about 10 pmol/kg/min. 
     
     
         3 . The method of  claim 1  wherein the composition is administered in a dose of from about 0.01 pmol/kg to 20 nmol/kg. 
     
     
         4 . The method of  claim 1  wherein the composition is administered as a single injection in a dose of from about 0.005 nmol/kg to 20 nmol/kg. 
     
     
         5 . The method of  claim 1  wherein the composition is administered concurrently with glucose. 
     
     
         6 . The method of  claim 1  wherein the composition is administered concurrently with potassium. 
     
     
         7 . The method of  claim 1  wherein the composition is administered concurrently with a free radical scavenger. 
     
     
         8 . The method of  claim 1  wherein the composition is administered within four hours of an ischemic event. 
     
     
         9 . The method of  claim 8  wherein the composition continues to be administered following the ischemic event. 
     
     
         10 . The method of  claim 1  wherein the composition is administered concurrently or as soon as possible following therapies that reestablish flow in an artery that has been obstructed. 
     
     
         11 . The method of  claim 1  wherein the composition is administered following a cardiac intervention selected from the group consisting of angioplasty, coronary bypass grafting, and placement of an intracoronary stent. 
     
     
         12 . The method of  claim 11  wherein the composition continues to be administered following the intervention. 
     
     
         13 . The method of  claim 1  wherein the composition is administered to treat ventricular arrhythmias. 
     
     
         14 . The method of  claim 13  wherein the ventricular arrhythmia is caused by a condition selected from the group consisting of cardiac ischemia, cardiac ischemia-reperfusion, and congestive heart failure.