Cardioprotective effects of ghrh agonists

Abstract

Disclosed herein are methods demonstrating that growth-hormone releasing hormone (GHRH) directly activates cellular reparative mechanisms within the injured heart, in a GH/IGF-I independent fashion. Following experimental myocardial infarction (MI), rats were randomly assigned to receive, during a 4 week period, either placebo (n=14), rat recombinant GH (rrGH, n=8) or JI-38 (n=8; 50 μg/Kg/day), a potent GHRH-agonist. JI-38 did not elevate serum levels of GH or IGF-I, but markedly attenuated the degree of cardiac functional decline and remodeling after injury. In contrast, GH administration markedly elevated body weight, heart weight, circulating GH and IGF-I, but did not offset the decline in cardiac structure and function. Whereas, both JI-38 and GH augmented levels of cardiac precursor cell proliferation, only JI-38 increased anti-apoptotic gene expression. Collectively, these findings demonstrate that within the heart, GHRH-agonists can activate cardiac repair following MI.

We claim: 
     
         1 . A method of treating a subject having myocardial ischemia comprising administering to the subject a therapeutic amount of a peptide selected from synthetic growth hormone releasing hormone (GHRH) and GHRH-A. 
     
     
         2 . The method of  claim 1 , wherein the method comprises administering GHRH-A. 
     
     
         3 . The method of  claim 1 , wherein the peptide administration is at a dosage of 50 μg/kg. 
     
     
         4 . The method of  claim 1 , wherein the peptide is administered subcutaneously. 
     
     
         5 . A method of treating a subject having myocardial fibrosis comprising administering to the subject a therapeutic amount of a peptide selected from synthetic growth hormone releasing hormone (GHRH) and GHRH-A. 
     
     
         6 . The method of  claim 5 , wherein the method comprises administering GHRH-A. 
     
     
         7 . The method of  claim 5 , wherein the peptide administration is at a dosage of 50 μg/kg. 
     
     
         8 . The method of  claim 5 , wherein the peptide is administered subcutaneously. 
     
     
         9 . A method of treating a subject having congestive heart failure comprising administering to the subject a therapeutic amount of a peptide selected from synthetic growth hormone releasing hormone (GHRH) and GHRH-A. 
     
     
         10 . The method of  claim 9 , wherein the method comprises administering GHRH-A. 
     
     
         11 . The method of  claim 9 , wherein the peptide administration is at a dosage of 50 μg/kg. 
     
     
         12 . The method of  claim 9 , wherein the peptide is administered subcutaneously. 
     
     
         13 . A method of regenerating damaged cardiac myocytes in a subject having a cardiac disease comprising administering to the subject a therapeutic amount of a peptide selected from synthetic growth hormone releasing hormone (GHRH) and GHRH-A. 
     
     
         14 . The method of  claim 13 , wherein the method comprises administering GHRH-A. 
     
     
         15 . The method of  claim 13 , wherein the peptide administration is at a dosage of 50 μg/kg. 
     
     
         16 . The method of  claim 13 , wherein the peptide is administered subcutaneously.