Grant: Operating Grant

When the left ventricle (LV) contracts, it forcefully propels blood into the arterial system. Therefore, it may seem surprising that some of the vital organs (e.g., the brain, and the heart itself) derive most of their blood flow not when the LV is contracting but later, when the LV is relaxing. This is possible because when the LV contracts, it "stores" much of its ejected blood in an arterial reservoir and this stored blood is distributed later, during diastole. Previous approaches could not provide an adequate conceptual framework but we have developed a promising new "reservoir-wave approach". The objective of this proposal is to understand better how blood flow is distributed to the vital organs of the body, to each according to its changing needs. We will measure blood flow in the human brain and pressure by non-invasive techniques. Preliminary data suggest that we can explain how brain flow responds to changes in O2 and CO2. By also measuring blood flow and pressure in the leg, we can study the effect of exercise and determine if exercise compromises brain flow. Previously, in dogs, we studied the coronary circulation, at rest and under the influence of drugs that increased or decreased blood flow. We will re-analyze those data based on our new understanding of the arterial reservoir. The innovative feature of this project is our conceptual framework and we believe this new approach will help us understand better how blood is distributed to vital organs. An adequate volume in the arterial reservoir is necessary to maintain blood flow to the brain and heart. This volume decreases when we get older, because the vessels get stiffer. Exercise and drugs that interfere with the action of a natural hormone (i.e., angiotensin) can increase the volume (i.e., decrease the stiffness) of this reservoir. Demonstrating how this reservoir works might persuade people to exercise more and lead to the development of new drugs.