The National Institutes of Health has renewed for another four years funding for a Wayne State University School of Medicine researcher studying the mechanisms that mediate dangerously high levels of sympathetic activity experienced by heart failure patients engaging in strenuous exercise.

The RO1 grant renewal for “Blood Pressure Control During Exercise in Heart Failure,” led by Donal O’Leary, Ph.D., professor and director of Cardiovascular Research in the Department of Physiology, totals $2,786,352. The renewal proposal received a score of top 2% from the study section review on its first submission for competitive renewal. The NIH has continuously funded the study since 1996, which has been funded six consecutive times and will span more than 30 years of funding.

During exercise, some patients can experience significant increases in sympathetic nerve activity, a condition that can cause constriction of coronary circulation, limiting oxygen supply to the heart and further decreasing the ability of the heart to pump blood.

Heart failure is one the leading causes of hospitalization and readmissions, and is associated with related clinical conditions, including peripheral claudication, a narrowing of arteries in the limbs that restricts blood flow, as well as kidney failure and stroke. When these patients perform even moderate exercise, they can experience severe cardiovascular responses. The cause of these abnormally excessive cardiovascular responses in patients with heart failure is poorly understood.

Dr. O'Leary is researching the causes of these adverse reactions with the aim of determining methods to prevent the circulatory constriction.

The systems that mediate abnormal cardiovascular response to exercise in patients with heart failure are unknown. Studies have demonstrated that activation of metabolically sensitive nerves within active skeletal muscle can produce significant increases in sympathetic nerve activity, called the muscle metaboreflex. Impaired cardiac function in heart patients may lead to decreased skeletal muscle blood flow during exercise, resulting in excessive activation of the muscle metaboreflex.

Dr. O’Leary has developed an innovative and technically complex instrumented model that allows continuous beat-by-beat monitoring of systemic hemodynamic parameters and multiple indices of ventricular function to assess the strength and mechanisms of cardiovascular reflexes at rest and during exercise.

The study's results, he said, may aid in the prescription of exercise regimes tailored for heart failure patients without pushing them to the brink of cardiovascular failure or stroke. The research may also help determine methods to prevent excessive sympathetic nerve activation during exercise.

Dr. O’Leary credited his staff “of dedicated and hard-working undergraduate students, graduate students, post-doctoral fellows, research assistants, research associates and colleagues for the ability to obtain funding for these studies over these many years.”

The NIH grant number is HL-55473.