New Findings What is the central question of this study?Do low‐frequency oscillations in arterial pressure and cerebral blood velocity protect cerebral blood velocity and oxygenation during central hypovolaemia? What is the main finding and its importance?Low‐frequency oscillations in arterial pressure and cerebral blood velocity attenuate reductions in cerebral oxygen saturation but do not protect absolute cerebral blood velocity during central hypovolaemia. This finding indicates the potential importance of haemodynamic oscillations in maintaining cerebral oxygenation and therefore viability of tissues during challenges to cerebral blood flow and oxygen delivery. Abstract Tolerance to both real and simulated haemorrhage varies between individuals. Exaggerated low‐frequency (∼0.1 Hz) oscillations in mean arterial pressure and brain blood flow [indexed via middle cerebral artery velocity (MCAv)] have been associated with improved tolerance to reduced central blood volume. The mechanism for this association has not been explored. We hypothesized that inducing low‐frequency oscillations in arterial pressure and cerebral blood velocity would attenuate reductions in cerebral blood velocity and oxygenation during simulated haemorrhage. Fourteen subjects (11 men and three women) were exposed to oscillatory (0.1 and 0.05 Hz) and non‐oscillatory (0 Hz) lower‐body negative pressure profiles with an average chamber pressure of −60 mmHg (randomized and counterbalanced order). Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe via near‐infrared spectroscopy. Tolerance was higher during the two oscillatory profiles compared with the 0 Hz profile (0.05 Hz, P = 0.04; 0.1 Hz, P = 0.09), accompanied by attenuated reductions in stroke volume (P < 0.001) and cerebral oxygenation of the frontal lobe (P ≤ 0.02). No differences were observed between profiles for reductions in mean arterial pressure (P = 0.17) and MCAv (P = 0.30). In partial support of our hypothesis, cerebral oxygenation, but not cerebral blood velocity, was protected during the oscillatory profiles. Interestingly, more subjects tolerated the oscillatory profiles compared with the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of haemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissues during haemorrhagic stress.

Trauma-induced hemorrhage is a leading cause of disability and death due, in part, to impaired perfusion and oxygenation of the brain. It is unknown if cerebrovascular responses to blood loss are differentiated based on sex. We hypothesized that compared to males, females would have reduced tolerance to simulated hemorrhage induced by maximal lower body negative pressure (LBNP), and this would be associated with an earlier reduction in cerebral blood flow and cerebral oxygenation. Methods: Healthy young males (n=29, 26±4 y) and females (n=23, 27±5 y) completed a step-wise LBNP protocol to presyncope. Mean arterial pressure (MAP), stroke volume (SV), middle cerebral artery velocity (MCAv), end-tidal CO2 (etCO2), and cerebral oxygen saturation (ScO2) were measured continuously. Results: Unexpectedly, tolerance to LBNP was similar between the sexes (males, 1604±68 s vs. females, 1453±78 s; P=0.15). Accordingly, decreases (%Δ) in MAP, SV, MCAv, and ScO2 were similar between males and females throughout LBNP and at presyncope (P≥0.20). Interestingly, while decreases in etCO2 were similar between the sexes throughout LBNP (P=0.16), at presyncope, the %Δ etCO2 from baseline was greater in males compared to females (-30.8±2.6% vs. -21.3±3.0%; P=0.02). Conclusion: Contrary to our hypothesis, sex does not influence tolerance, or the central or cerebral hemodynamic responses to simulated hemorrhage. However, the etCO2 responses at presyncope do suggest potential sex differences in cerebral vascular sensitivity to CO2 during central hypovolemia.

Haemodynamic oscillations occurring at frequencies below the rate of respiration have been observed experimentally for more than a century. Much of the research regarding these oscillations, observed in arterial pressure and blood flow, has focused on mechanisms of generation and methods of quantification. However, examination of the physiological role of these oscillations has been limited. Multiple studies have demonstrated that oscillations in arterial pressure and blood flow are associated with the protection in tissue oxygenation or functional capillary density during conditions of reduced tissue perfusion. There is also evidence that oscillatory blood flow can improve clearance of interstitial fluid, with a growing number of studies demonstrating a role for oscillatory blood flow to aid in clearance of debris from the brain. The therapeutic potential of these haemodynamic oscillations is an important new area of research which may have beneficial impact in treating conditions such as stroke, cardiac arrest, blood loss injuries, sepsis, or even Alzheimer's disease and vascular dementia.

Introduction. Oscillatory patterns in arterial pressure and blood flow (at ∼0.1 Hz) may protect tissue oxygenation during conditions of reduced cerebral perfusion and/or hypoxia. We hypothesized that inducing oscillations in arterial pressure and cerebral blood flow at 0.1 Hz would protect cerebral blood flow and cerebral tissue oxygen saturation during exposure to a combination of simulated hemorrhage and sustained hypobaric hypoxia. Methods. Eight healthy human subjects (4 male, 4 female; 30.1 ± 7.6 year) participated in two experiments at high altitude (White Mountain, California, USA; altitude, 3800 m) following rapid ascent and 5–7 d of acclimatization: (1) static lower body negative pressure (LBNP, control condition) was used to induce central hypovolemia by reducing chamber pressure to −60 mmHg for 10 min (0 Hz), and; (2) oscillatory LBNP where chamber pressure was reduced to −60 mmHg, then oscillated every 5 s between −30 mmHg and −90 mmHg for 10 min (0.1 Hz). Measurements included arterial pressure, internal carotid artery (ICA) blood flow, middle cerebral artery velocity (MCAv), and cerebral tissue oxygen saturation (ScO2). Results. Forced 0.1 Hz oscillations in mean arterial pressure and mean MCAv were accompanied by a protection of ScO2 (0.1 Hz: −0.67% ± 1.0%; 0 Hz: −4.07% ± 2.0%; P = 0.01). However, the 0.1 Hz profile did not protect against reductions in ICA blood flow (0.1 Hz: −32.5% ± 4.5%; 0 Hz: −19.9% ± 8.9%; P = 0.24) or mean MCAv (0.1 Hz: −18.5% ± 3.4%; 0 Hz: −15.3% ± 5.4%; P = 0.16). Conclusions. Induced oscillatory arterial pressure and cerebral blood flow led to protection of ScO2 during combined simulated hemorrhage and sustained hypoxia. This protection was not associated with the preservation of cerebral blood flow suggesting preservation of ScO2 may be due to mechanisms occurring within the microvasculature.

Lower body negative pressure (LBNP) elicits central hypovolemia, and has been used to simulate the cardiovascular and cerebrovascular responses to hemorrhage in humans. LBNP protocols commonly employ progressive stepwise reductions in chamber pressure for specific time periods. However, continuous ramp LBNP protocols have also been utilized to simulate the continuous nature of most bleeding injuries. The aim of this study was to compare tolerance and hemodynamic responses between these two LBNP profiles. Healthy human subjects (N=19; age, 27±4 y; 7F/12M) completed a 1) step LBNP protocol (5-min steps), and; 2) continuous ramp LBNP protocol (3 mmHg/min), both to presyncope. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), cerebral oxygen saturation (ScO2), and end-tidal CO2 (etCO2) were measured. LBNP tolerance, via the cumulative stress index (CSI, summation of chamber pressure*time at each pressure), and hemodynamic responses were compared between the two protocols. The CSI (Step: 911±97 mmHg*min vs. Ramp: 823±83 mmHg*min; P=0.12) and the magnitude of central hypovolemia (%Δ SV, Step: -54.6±2.6 % vs. Ramp: -52.1±2.8 %; P=0.32) were similar between protocols. While there were no differences between protocols for the maximal %Δ HR (P=0.88), the %Δ MAP during the step protocol was attenuated (P=0.05), and the reductions in MCAv, PCAv, ScO2, and etCO2 were greater (P≤0.08) when compared with the ramp protocol at presyncope. These results indicate that when comparing cardiovascular responses to LBNP across different laboratories, the specific pressure profile must be considered as a potential confounding factor.