May 8, 2017

NIH awards Dr. O'Leary another R01 grant for heart failure-exercise study

A Wayne State University School of Medicine researcher has secured another four-year R01 grant totaling $1,633,788 from the National Institutes of Health to study the mechanisms that mediate dangerously high levels of sympathetic activity experienced by heart failure patients engaging in strenuous exercise.

These patients can experience during exercise significant increases in sympathetic nerve activity, which can constrict coronary circulation, thereby 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 myriad related clinical conditions, including peripheral claudication, stroke and renal failure. When these patients exercise, often profound cardiovascular responses occur despite only relatively modest exercise workloads. What cause these abnormally excessive cardiovascular responses to exercise in patients with heart failure in poorly understood, and therefore difficult to prevent.

In "Blood Pressure Control During Exercise in Heart Failure," Donal O'Leary, Ph.D., professor of Physiology and director of Cardiovascular Research, is researching the causes of these adverse reactions. This study, first funded in 1996 and now extended to 2021, marks 26 years of continuous NIH funding on this grant project.

The systems that mediate abnormal cardiovascular response to exercise in those 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 may lead to decreased skeletal muscle blood flow during exercise, resulting in excessive activation of the muscle metaboreflex.

Dr. O'Leary's laboratory is uniquely poised to address this issue. He has developed an innovative and technically complex instrumented animal 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. Further, these studies may point a way to prevent excessive sympathetic nerve activation during exercise.

The NIH grant number is HL-55473.