Project 171113

Heart failure is a progressive disease, slowly, but surely disabling the patient. In recent years, it has become clear that besides the initial abnormality in the heart (eg heart attack) increased activity of the sympathetic nervous system to the heart plays a major role in the progression of heart failure to terminal disease. Why the sympathetic nervous system shows this increase is not yet understood. The present project has demonstrated that in rats a myocardial infarction ("heart attack") leads to activation of brain pathways involving a cascade of factors. This cascade causes not only persistent and progressive increase in sympathetic activity but also the progression of the disease. These studies have provided major new insights into the mechanisms leading to the progression of heart failure, which in a later phase, may lead to new approaches to the prevention of progression of heart failure. In studies outlined in this grant proposal we will assess 1) peripheral mechanisms responsible for activation of the brain-pathways involved in the increase in sympathetic activity and 2) sympathetic activity specifically to the heart and kidneys, and its role in the progression of heart failure.

using a rat model of myocardial infarction to study the brain pathways involved in sympathetic hyperactivity and the progression of heart failure