Pulsatile Perfusion Therapy at 0.1 Hz protects internal carotid artery blood flow and cerebral tissue oxygenation in humans during simulated hemorrhage

Background: Pulsatile Perfusion Therapy (PPT) is a method we have developed to induce hemodynamic oscillations at 0.1 Hz, which are associated with protection of tissue oxygenation during conditions of reduced tissue perfusion. We previously demonstrated that PPT, via oscillatory lower body negative pressure (LBNP), protected cerebral tissue oxygenation (ScO 2 ) without affecting middle cerebral artery blood velocity (MCAv) responses during simulated hemorrhage via LBNP in humans. We have since developed a new approach to administer PPT via rapid inflatable thigh cuffs to achieve similar 0.1 Hz hemodynamic oscillations. We hypothesized that PPT induced via thigh cuffs would also protect ScO 2 without affecting cerebral blood flow during simulated hemorrhage in humans. Methods: 14 young and healthy participants (9M/5F; aged 26.0 ± 4.6 y) completed two experimental protocols in which they underwent −60 mmHg LBNP for up to 10-min. In the PPT condition, 0.1 Hz hemodynamic oscillations were induced by intermittently inflating and deflating bilateral thigh cuffs (0–230 mmHg) in 10-s cycles for the duration of the LBNP protocol. In the control condition (CON), thigh cuffs were in place but remained inactive throughout the entire protocol. The order of PPT and CON were randomized. Beat-to-beat arterial pressure was measured via finger photoplethysmography. Cerebral blood flow was indexed by internal carotid artery (ICA) blood flow (via duplex Doppler ultrasound) and by MCAv (via transcranial Doppler ultrasound). ScO 2 was measured via near-infrared spectroscopy. Fast Fourier transform analysis was used to assess the amplitude of 0.1 Hz oscillations in mean arterial pressure (MAP) and MCAv. Results: PPT induced greater 0.1 Hz oscillations in MAP (PPT: 70.5 ± 68.2 fold vs. CON: 6.7 ± 10.6 fold from baseline; P < 0.01) and MCAv (PPT: 31.1 ± 30.3 fold vs. CON: 3.6 ± 3.6 fold from baseline; P = 0.01) compared to CON. PPT attenuated reductions in ICA blood flow (PPT: −17.5 ± 13.6% vs. CON: −32.4 ± 16.4% from baseline; P < 0.01) compared to CON, but did not affect MCAv responses (PPT: −18.4 ± 9.3% vs. CON: −20.6 ± 13.5% from baseline; P = 0.58). PPT also attenuated reductions in ScO 2 (PPT: −5.5 ± 3.2% vs. CON: −8.0 ± 3.1% from baseline; P = 0.04) compared to CON. Conclusions: PPT via thigh cuffs protected cerebral tissue oxygenation in humans during simulated hemorrhage via LBNP. PPT also protected cerebral blood flow responses, indexed by ICA blood flow, but not MCAv. These data add further evidence for the potential use of 0.1 Hz hemodynamic oscillations as a therapeutic intervention for the treatment of hemorrhage, and other conditions of cerebral hypoperfusion. AHA Transformational Project Award (19TPA34910073; to CAR); AHA Predoctoral Fellowship (23PRE1018469; to KAD); NIH T32 predoctoral fellowship (T32 AG 020494; to KAD and VQD) 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.