Rickards, Caroline A.2024-06-142024-06-142024-05https://hdl.handle.net/20.500.12503/32862Inducing 0.1 Hz (10-s cycle) oscillations in cerebral blood flow attenuates the reduction in cerebral tissue oxygenation during simulated hemorrhage in humans. Our laboratory has developed a potential therapeutic technique called pulsatile perfusion therapy (PPT) which induces 0.1 Hz oscillations in cerebral blood flow. It is unknown, however, how stiffness of the arteries influences the magnitude of cerebral blood flow oscillations, and/or the protection of cerebral tissue oxygenation. When 0.1 Hz oscillations are induced during simulated hemorrhage, we hypothesized that: 1) arterial stiffness of the internal carotid artery (ICA) and common carotid artery (CCA) would increase from rest; 2) the amplitude of 0.1 Hz oscillations in cerebral blood flow would be higher in individuals with stiffer arteries, and; 3) the reduction in cerebral tissue oxygenation would be smaller with higher amplitude of cerebral blood flow oscillations. Two studies using two different techniques of PPT were performed to investigate these hypotheses. Study 1: In a retrospective analysis, 8 healthy human participants (age: 30.1±7.6 y) underwent a 10-min hypovolemic oscillatory lower body negative pressure (OLBNP) protocol, where chamber pressure oscillated every 5-s between -30 mmHg and -90 mmHg (i.e., 0.1 Hz). ICA β-stiffness index was calculated from measurements of ICA diameter (via ultrasound imaging), and arterial pressure (via finger photoplethysmography). Middle cerebral artery velocity (MCAv) was measured using transcranial doppler ultrasound, and cerebral tissue oxygenation (ScO2) was measured with near infrared spectroscopy. Fast Fourier transformation was used to quantify oscillations in mean MCAv at ~0.1 Hz. While mean MCAv 0.1 Hz oscillations increased from baseline to OLBNP (N=8, 34.0±33.9 (cm/s)2 vs. 104.7±58.1 (cm/s)2, p=0.01), ICA β stiffness did not increase (N=5, 6.1±0.7 au vs. 8.2±2.7 au, p=0.21). There was no relationship between baseline ICA β-stiffness and the percent change in mean MCAv 0.1 Hz oscillations (N=5; r=0.44, p=0.46). ScO2 decreased from baseline to OLBNP (N=8, 66.5±2.9 % vs. 64.8±2.9 %, p=0.03), but there was also no relationship between the percent change in mean MCAv 0.1 Hz oscillations and the decrease in ScO2 (r=0.28, p=0.50). Study 2: In a prospective pilot study, 3 participants underwent a 10-min LBNP protocol to a chamber pressure of -60 mmHg, and hemodynamic oscillations were simultaneously induced with bilateral thigh cuffs inflating for 5-s to 230 mmHg then deflating for 5-s in a 10-s cycle (i.e., 0.1 Hz). β-stiffness index of the CCA was measured. In this pilot study, insufficient data were collected to perform statistics for each of the three aims, so descriptive results are presented. Adequate ultrasound measurements were made for assessment of CCA β- stiffness in two participants; in the control condition, CCA β-stiffness was 6.7 ± 2.4 au during baseline and increased to 7.4 ± 1.1 au during LBNP (N=2). With PPT, CCA β-stiffness was 6.6 ± 1.6 au during baseline and increased to 7.8 ± 2.2 au during LBNP (N=2). The amplitude of MCAv 0.1 Hz oscillations increased from 7.9 (cm/s)2 at baseline of the control condition to 179.8 (cm/s)2 (i.e., a ~23-fold increase) during LBNP. The amplitude of MCAv 0.1 Hz oscillations increased from 25.8 (cm/s)2 during baseline of PPT to 210.2 (cm/s)2 (~8-fold increase) during LBNP (N=1). ScO2 decreased from 75.0% to 71.3% during LBNP in the control condition, and from 73.4% to 71.6% in the PPT condition (N=1). Based on the results of Study 1, 0.1 Hz OLBNP does not increase ICA stiffness, and there is no relationship between ICA stiffness, amplitude of induced 0.1 Hz cerebral blood flow oscillations, and the reduction in cerebral tissue oxygenation during simulated hemorrhage. However, as this analysis was performed retrospectively, and arterial stiffness was not initially an outcome measure, there were limited data available for analysis. For Study 2, we were successfully able to induce 0.1 Hz oscillations in cerebral blood flow by combining LBNP with bilateral thigh cuff inflations. However, insufficient data were available to make definitive conclusions about the role of PPT on CCA β-stiffness, 0.1 Hz oscillations in cerebral blood flow, or the relationship in 0.1 Hz oscillations in cerebral blood flow and protection of cerebral tissue oxygenation. This study is currently ongoing, and additional data will provide further insight into these relationships.application/pdfenarterial stiffnesscerebral blood flow oscillationsVascular StiffnessCerebrovascular CirculationPulsatile FlowThesis