Grant: Operating Grant

Congestive heart failure is an important health problem affecting more than 350,000 Canadians. Subjects with heart failure are principally limited because of shortness of breath that, according to disease severity, can interfere with daily activities or even occur at rest. This symptom has been attributed to passive congestion of the lung with blood because of failure of the heart to pump efficiently, akin to a dam on a lake. Although blood congestion into the lungs no doubt contributes to the process, reactive structural modifications of the lung itself with thickening of the wall between the air spaces and the lung vessels play a more important deleterious role. This thickening (remodeling) of the lung will reduce the capacity for oxygen to enter into the blood and elevatre the pressure in the lung, further increasing the work demand of the right side of the heart. There have been deceivingly little research efforts to study the evolution and the determinants of lung remodeling in congestive heart failure. Osteopontin is a substance that is known to be involved in various lung disorders, but its role in lung disease associated with heart failure is unknown. The drug spironolactone is recommended for the treatment of advanced heart failure: its mechanisms of action are however still unclear and it is unfortunately under-used. This grant application proposes to evaluate the hypothesis that increased lung production of osteopontin contributes to lung remodeling and that the drug spironolatone can block osteopontin activation and improve lung function in heart failure. The results of this grant will provide a better understanding of the processes responsible for the major symptom of heart failure, shortness of breath, and explore a novel pharmacological pathway for subjects suffering from heart failure.