Hemodynamic Oscillations: Physiological Consequences and Therapeutic Potential

Hemorrhage, or massive blood loss, continues to be a leading cause of preventable death. Therapeutic approaches that protect vital organ function are needed to improve outcomes from hemorrhage. In this dissertation, I explored the use of hemodynamic oscillations below the respiratory frequency (i.e., oscillations in arterial pressure and cerebral blood flow) as a novel technique for protecting tissue oxygenation during hemorrhage. In the first study of this dissertation, I hypothesized that hemodynamic oscillations would contribute to improved tolerance to central hypovolemia simulating hemorrhage. In further assessing the role of arterial blood gases on the physiological responses to forcing hemodynamic oscillations during a simulated hemorrhage, I hypothesized that forcing hemodynamic oscillations during simulated hemorrhage would protect tissue oxygenation during conditions of hypoxia and isocapnia, and improve cerebral blood flow. I also hypothesized that this protection would occur equally for both females and males. To address these hypotheses, I conducted five independent studies using lower body negative pressure as a method of simulating hemorrhage in healthy, conscious humans: in one study I utilized a maximal step-wise LBNP protocol to assess endogenous hemodynamic oscillations and tolerance to simulated hemorrhage, and in the remaining 4 studies, I utilized oscillatory and non-oscillatory LBNP to assess the potential therapeutic utility of forcing hemodynamic oscillations during simulated hemorrhage. The major findings from these investigations were: 1) greater amplitude of low frequency oscillations in arterial pressure are associated with greater LBNP tolerance, but the relative time to peak oscillatory power was not dependent on tolerance; 2) forced hemodynamic oscillations protect cerebral tissue oxygenation without protecting cerebral blood flow during the combined stress of simulated hemorrhage and hypobaric hypoxia; 3) isocapnia with simulated hemorrhage prevents the reduction in cerebral blood flow and tissue oxygenation, and forced hemodynamic oscillations during this stress protects stroke volume and arterial pressure; 4) females exhibit protected muscle tissue oxygenation to simulated hemorrhage, and the reduction in muscle tissue oxygenation in males can be attenuated with forced hemodynamic oscillations; and 5) forced hemodynamic oscillations at high altitude are greater in amplitude and result in similar protection of cerebral tissue oxygenation as low altitude conditions. These findings contribute to the growing body of literature highlighting the potential utility of oscillatory hemodynamics for therapeutic application.