Induced 0.1 Hz hemodynamic oscillations protect peripheral tissue oxygenation despite no effect on vascular conductance during simulated hemorrhage in humans

Background: High amplitude 0.1 Hz (~10-s cycle) oscillations in arterial pressure and blood flow are observed in humans with high tolerance to simulated blood loss. We have shown that experimentally induced hemodynamic oscillations (i.e., Pulsatile Perfusion Therapy, PPT) increases tolerance to simulated blood loss and protects tissue oxygenation. Increases in sympathetic activity are associated with a greater amplitude of spontaneous 0.1 Hz blood pressure and blood flow oscillations, but it is not known if induced arterial pressure oscillations at 0.1 Hz can lead to increases in sympathetic activity. Hypothesis: Induced 0.1 Hz oscillations in arterial pressure and blood flow during simulated blood loss increases sympathetic activity, indexed by a decrease in peripheral vascular conductance. Methods: Thirteen healthy humans (8M, 5F; aged 25.9 ± 4.8 y) completed two bouts of -60 mmHg lower body negative pressure (LBNP) for 10-min each, separated by at least 15-min of recovery. In the PPT condition, 0.1 Hz hemodynamic oscillations were induced by inflating and deflating bilateral thigh cuffs every 5-s (10-s cycle) between 0-230 mmHg. During the control condition (CON), the thigh cuffs were inactive throughout the LBNP protocol. The order of conditions was randomized and counterbalanced. Mean arterial pressure (MAP), brachial artery (BA) blood flow (via velocity and vessel cross-sectional area), and forearm muscle tissue oxygenation (SmO 2 ) were measured continuously. BA conductance was calculated by dividing BA blood flow by MAP. Results: During LBNP, the amplitude of 0.1 Hz oscillations in MAP (CON: 73.5 ± 66.2 mmHg 2 vs. PPT: 715.0 ± 519.8 mmHg 2 ; p<0.01) and BA blood velocity (CON: 2.7 ± 2.3 (cm/s) 2 vs. PPT: 25.1 ± 18.4 (cm/s) 2 , p<0.01) were greater with PPT compared with CON. Simulated hemorrhage via LBNP with and without PPT had similar effects on MAP (CON, baseline: 97.9 ± 7.5 mmHg vs. LBNP: 81.1 ± 8.4 mmHg, p<0.01; PPT, baseline: 99.0 ± 9.3 mmHg vs. LBNP: 84.9 ± 10.9 mmHg, p<0.01; Condition Effect: p=0.33), BA blood flow (CON, baseline: 39.2 ± 21.1 ml/min vs. LBNP: 23.0 ± 8.1 ml/min, p<0.01; PPT, baseline: 42.1 ± 23.7 ml/min vs. LBNP: 25.4 ± 12.3 ml/min, p<0.01; Condition Effect: p=0.29), and BA conductance (CON, baseline: 0.41 ± 0.20 ml/min/mmHg vs. LBNP: 0.28 ± 0.08 ml/min/mmHg, p=0.04; PPT, baseline: 0.42 ± 0.24 ml/min/mmHg vs. LBNP: 0.31 ± 0.14 ml/min/mmHg, p=0.04; Condition Effect: p=0.60). However, during LBNP, absolute SmO 2 was greater with PPT compared with CON (CON, baseline: 71.5 ± 6.3 % vs. LBNP: 63.1 ± 6.9%, p<0.01; PPT, baseline: 72.9 ± 7.1 % vs. LBNP: 65.4 ± 7.3%, p<0.01; Condition Effect: p=0.03). Conclusions: These data suggest that PPT does not alter peripheral blood flow or peripheral vascular conductance during simulated hemorrhage in humans, but does protect tissue oxygenation. Analysis of plasma catecholamines is planned from blood samples collected from these participants as a more direct measure of sympathetic activity. These findings add further support for the potential use of 0.1 Hz hemodynamic oscillations as a therapeutic intervention for conditions associated with vital organ ischemia such as hemorrhage, stroke, myocardial infarction, and sepsis. American Heart Association Predoctoral Fellowship (23PRE1018469; KAD) American Heart Association Transformational Project Award (19TPA34910743; CAR) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.