Inorganic nitrite to improve cardiopulmonary hemodynamics

Abstract

Disclosed herein are methods for treating acute or chronic heart failure using inorganic nitrite, such as sodium nitrite. Sodium nitrite is a naturally occurring compound that is commonly used as a preservative in meats. Due to its vasodilative properties and involvement in the nitric oxide pathway, drug development companies and researchers are also investigating sodium nitrite as a therapeutic agent.

1 . A method for treating heart failure with preserved ejection fraction (HFpEF) comprising administering to a subject in need of treatment a therapeutically effective amount of inorganic nitrite. 
     
     
         2 . The method of  claim 1 , wherein the nitrite is administered by inhalation. 
     
     
         3 . The method of  claim 2 , wherein the nitrite is nebulized. 
     
     
         4 . The method of  claim 3 , wherein the nitrite is administered at an emitted dose of about 90 mg or less. 
     
     
         5 . The method of  claim 3 , wherein the nitrite is administered at an emitted dose of about 45 mg to about 90 mg. 
     
     
         6 . The method of  claim 3 , wherein the nitrite is administered at an emitted dose of about 25 mg to about 80 mg. 
     
     
         7 . The method of  claim 2 , wherein the nitrite is administered in an escalated titrated dose. 
     
     
         8 . The method of  claim 7 , wherein the nitrite is administered at one or more doses lower than about 90 mg, followed by one or more doses that escalate to a final emitted dose at about 80 mg to about 90 mg. 
     
     
         9 . The method of  claim 2 , wherein the inhaled nitrite is a liquid formulation. 
     
     
         10 . The method of  claim 9 , wherein the inhaled nitrite is nebulized. 
     
     
         11 . The method of  claim 2 , wherein the inhaled nitrite is a dry powder formulation. 
     
     
         12 . The method of  claim 1 , wherein the nitrite is sodium nitrite. 
     
     
         13 . The method of  claim 1 , wherein the administration of inorganic nitrite results in a decrease in one or more of right atrial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance. 
     
     
         14 . The method of  claim 1 , wherein the administration of inorganic nitrite results in an improved cardiac index. 
     
     
         15 . The method of  claim 1 , wherein the administration of inorganic nitrite results in increased exercise capacity. 
     
     
         16 . The method of  claim 1 , wherein the HFpEF is associated with pulmonary hypertension. 
     
     
         17 . A method of decreasing one or more of pulmonary capillary wedge pressure, right atrial pressure and pulmonary arterial pressure in a subject in need of treatment with a condition that results in one or more of increased pulmonary capillary wedge pressure, right atrial pressure and pulmonary arterial pressure comprising administering a therapeutically effective dose of inorganic nitrite and wherein such administration does not cause a significant drop in blood pressure and increase in heart rate, wherein the subject has a condition selected from one or more of pulmonary hypertension associated with diastolic heart failure, pulmonary hypertension associated with systolic heart failure, interstitial lung disease, pulmonary arterial hypertension including associated pulmonary arterial hypertension, idiopathic pulmonary arterial hypertension; exercise intolerance, and sleep-disordered breathing-related pulmonary hypertension. 
     
     
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         30 . The method of  claim 1 , wherein the subject is administered a dose of inorganic nitrite at a dose of nitrite that results in a plasma concentration of nitrite of about 4 micromolar to about 15 micromolar nitrite. 
     
     
         31 . The method of  claim 1  wherein the inhaled inorganic nitrite is administered at a dose of nitrite that results in a plasma concentration of nitrite of about 4 micromolar to about 15 micromolar nitrite. 
     
     
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         49 . The method of  claim 15 , wherein the increase in exercise capacity is associated with a decrease in one or more of right atrial pressure, pulmonary capillary wedge pressure, or pulmonary vascular resistance.