Inotropic Effects of Antibodies on Cardiac Contraction

Abstract

The present invention shows that site-specific antibodies to the (Na + +K + )-ATPase exert a potent biological effect in cardiac myocytes and demonstrates a key structural region of the enzyme that participates in the regulation of cardiac contractility. These results establish an important link between a biological action and a precise molecular structure of the (Na + +K + )-ATPase. Furthermore, the antibody-induced positive inotropic effect is independent of inactivation of the enzyme may reveal a novel mode for (Na + +K + )-ATPase to regulate cardiac function. The data provide new molecular insights into the structural and functional relationship of the ubiquitous (Na + +K + )-ATPase.

What is claimed: 
     
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         43 . A therapeutically effective composition comprising an isolated and purified antibody which is specifically made against the synthetic amino acid sequence KRQPRNPKTDKLVNE (SEQ ID NO: 1), wherein the binding of said antibody in a therapeutically effective amount to the alpha-subunit of the (Na + +K + )-ATPase increases myocyte intracellular diastolic or systolic calcium without inhibiting (Na + +K + )-ATPase activity. 
     
     
         44 . The therapeutically effective composition of  claim 1 , wherein the binding of said antibody in a therapeutically effective amount to the (Na + +K + )-ATPase exerts a positive inotropic effect in cardiac myocytes or in a heart for the treatment of heart failure or heart muscle contractile disorders. 
     
     
         45 . The therapeutically effective composition of  claim 1 , wherein said antibody is specifically made against the synthetic amino acid sequence KRQPRNPKTDKLVNE (SEQ ID NO: 1), said synthetic amino acid sequence being a component of a vaccine. 
     
     
         46 . The therapeutically effective composition of  claim 1  wherein said composition can be administered to a mammalian patient in a therapeutically effective amount for the treatment of heart failure or heart muscle contractile disorders. 
     
     
         47 . The therapeutically effective composition of  claim 1 , wherein said antibody is a polyclonal antibody, a monoclonal antibody, a humanized antibody or a human antibody