Victoria Kay

The role of cerebral oxygenation and regional cerebral blood flow on tolerance to central hypovolemia

Tolerance to central hypovolemia is highly variable, and accumulating evidence suggests that protection of anterior cerebral blood flow (CBF) is not an underlying mechanism. We hypothesized that individuals with high tolerance to central hypovolemia would exhibit protection of cerebral oxygenation (ScO2), and prolonged preservation of CBF in the posterior vs. anterior cerebral circulation. Eighteen subjects (7 male/11 female) completed a presyncope-limited lower body negative pressure (LBNP) protocol (3 mmHg/min onset rate). ScO2 (via near-infrared spectroscopy), middle cerebral artery velocity (MCAv), posterior cerebral artery velocity (PCAv) (both via transcranial Doppler ultrasound), and arterial pressure (via finger photoplethysmography) were measured continuously. Subjects who completed ≥70 mmHg LBNP were classified as high tolerant (HT; n = 7) and low tolerant (LT; n = 11) if they completed ≤60 mmHg LBNP. The minimum difference in LBNP tolerance between groups was 193 s (LT = 1,243 ± 185 s vs. HT = 1,996 ± 212 s; P < 0.001; Cohens d = 3.8). Despite similar reductions in mean MCAv in both groups, ScO2 decreased in LT subjects from -15 mmHg LBNP (P = 0.002; Cohens d=1.8), but was maintained at baseline values until -75 mmHg LBNP in HT subjects (P < 0.001; Cohens d = 2.2); ScO2 was lower at -30 and -45 mmHg LBNP in LT subjects (P ≤ 0.02; Cohens d ≥ 1.1). Similarly, mean PCAv decreased below baseline from -30 mmHg LBNP in LT subjects (P = 0.004; Cohens d = 1.0), but remained unchanged from baseline in HT subjects until -75 mmHg (P = 0.006; Cohens d = 2.0); PCAv was lower at -30 and -45 mmHg LBNP in LT subjects (P ≤ 0.01; Cohens d ≥ 0.94). Individuals with higher tolerance to central hypovolemia exhibit prolonged preservation of CBF in the posterior cerebral circulation and sustained cerebral tissue oxygenation, both associated with a delay in the onset of presyncope.

Reproducibility of a continuous ramp lower body negative pressure protocol for simulating hemorrhage

Central hypovolemia elicited by application of lower body negative pressure (LBNP) has been used extensively to simulate hemorrhage in human subjects. Traditional LBNP protocols incorporate progressive steps in pressure held for specific time intervals. The aim of this study was to assess the reproducibility of applying continuous LBNP at a constant rate until presyncope to replicate actual bleeding. During two trials (≥4 weeks intervening), LBNP was applied at a rate of 3 mmHg/min in 18 healthy human subjects (12M; 6F) until the onset of presyncopal symptoms. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), total peripheral resistance (TPR), mean middle and posterior cerebral artery velocities (MCAv, PCAv), and cerebral oxygen saturation (ScO2) were measured continuously. Time to presyncope (TTPS) and hemodynamic responses were compared between the two trials. TTPS (1649 ± 98 sec vs. 1690 ± 88 sec; P = 0.47 [t‐test]; r = 0.77) and the subsequent magnitude of central hypovolemia (%Δ SV −54 ± 4% vs. −53 ± 4%; P = 0.55) were similar between trials. There were no statistically distinguishable differences at either baseline (P ≥ 0.17) or presyncope between trials for HR, MAP, TPR, mean MCAv, mean PCAv, or ScO2 (P ≥ 0.19). The rate of change from baseline to presyncope for all hemodynamic responses was also similar between trials (P ≥ 0.12). Continuous LBNP applied at a rate of 3 mmHg/min was reproducible in healthy human subjects, eliciting similar reductions in central blood volume and subsequent reflex hemodynamic responses.

Cerebral oxygenation and regional cerebral perfusion responses with resistance breathing during central hypovolemia

Resistance breathing improves tolerance to central hypovolemia induced by lower body negative pressure (LBNP), but this is not related to protection of anterior cerebral blood flow [indexed by mean middle cerebral artery velocity (MCAv)]. We hypothesized that inspiratory resistance breathing improves tolerance to central hypovolemia by maintaining cerebral oxygenation (ScO2), and protecting cerebral blood flow in the posterior cerebral circulation [indexed by posterior cerebral artery velocity (PCAv)]. Eight subjects (4 male/4 female) completed two experimental sessions of a presyncopal-limited LBNP protocol (3 mmHg/min onset rate) with and without (Control) resistance breathing via an impedance threshold device (ITD). ScO2 (via near-infrared spectroscopy), MCAv and PCAv (both via transcranial Doppler ultrasound), and arterial pressure (via finger photoplethysmography) were measured continuously. Hemodynamic responses were analyzed between the Control and ITD condition at baseline (T1) and the time representing 10 s before presyncope in the Control condition (T2). While breathing on the ITD increased LBNP tolerance from 1,506 ± 75 s to 1,704 ± 88 s (P = 0.003), both mean MCAv and mean PCAv were similar between conditions at T2 (P ≥ 0.46), and decreased by the same magnitude with and without ITD breathing (P ≥ 0.53). ScO2 also decreased by ~9% with or without ITD breathing at T2 (P = 0.97), and there were also no differences in deoxygenated (dHb) or oxygenated hemoglobin (HbO2) between conditions at T2 (P ≥ 0.43). There was no evidence that protection of regional cerebral blood velocity (i.e., anterior or posterior cerebral circulation) nor cerebral oxygen extraction played a key role in the determination of tolerance to central hypovolemia with resistance breathing.