The overall goal of the proposed research is to determine the effects of forcing 0.1 Hz oscillations in arterial pressure on cerebral blood flow and cerebral tissue oxygenation during simulated hemorrhage in humans. Hemorrhage challenges blood flow to the brain, an organ especially susceptible to disruptions in blood flow oxygen delivery. Therapies that preserve blood flow and oxygenation to the brain are needed to ensure tissue survival during hemorrhage. Previously, we have shown an association between spontaneous 0.1 Hz oscillations in arterial pressure and improved tolerance to reduced cerebral blood flow during central hypovolemia in humans. Our central hypothesis is that forcing 0.1 Hz oscillations in arterial pressure and cerebral blood flow will protect cerebral oxygenation during challenges to perfusion. In Specific Aim 1 we will measure blood flow to the brain through the internal carotid and vertebral arteries to assess the effects of 0.1 Hz oscillations in arterial pressure on inflow into the cerebral tissues under simulated hemorrhage conditions. We hypothesize that 0.1 Hz oscillations in arterial pressure will attenuate decreases in blood flow to the brain during simulated hemorrhage. Another factor that could contribute to protections in cerebral blood flow with oscillatory perfusion is redistribution of blood flow from peripheral tissues towards the brain. In Specific Aim 2 we will measure efferent sympathetic activity and neurovascular transduction to determine the effect of 0.1 Hz oscillations in arterial pressure on peripheral vasoconstriction under simulated hemorrhage conditions. We hypothesize that efferent sympathetic activity, neurovascular transduction and peripheral vasoconstriction will increase during simulated hemorrhage with applied 0.1 Hz oscillations, subsequently protecting central blood volume. The rationale for the proposed research is to develop a new intervention to treat reductions in cerebral blood flow and oxygenation in various clinical conditions such as hemorrhage, cardiac arrest, stroke, and sepsis. This approach is innovative in that it addresses a novel mechanism for maintaining cerebral tissue perfusion and oxygenation by utilizing 0.1 Hz oscillations in arterial pressure. This research will fill the gap in our knowledge regarding the potential utility of 0.1 Hz oscillations in arterial pressure on protecting cerebral blood flow and cerebral tissue oxygenation during conditions of reduced cerebral perfusion.
|Program type||Predoctoral Fellowship|
|Effective start/end date||01/01/2020 → 04/30/2022|