Effect of acute hypoxemia on cerebral blood flow velocity control during lower body negative pressure

Abstract

The ability to maintain adequate cerebral blood flow and oxygenation determines tolerance to central hypovolemia. We tested the hypothesis that acute hypoxemia during simulated blood loss in humans would cause impairments in cerebral blood flow control. Ten healthy subjects (32 ± 6 years, BMI 27 ± 2 kg·m−2) were exposed to stepwise lower body negative pressure (LBNP, 5 min at 0, −15, −30, and −45 mmHg) during both normoxia and hypoxia (FiO2 = 0.12–0.15 O2 titrated to an SaO2 of ~85%). Physiological responses during both protocols were expressed as absolute changes from baseline, one subject was excluded from analysis due to presyncope during the first stage of LBNP during hypoxia. LBNP induced greater reductions in mean arterial pressure during hypoxia versus normoxia (MAP, at −45 mmHg: −20 ± 3 vs. −5 ± 3 mmHg, P < 0.01). Despite differences in MAP, middle cerebral artery velocity responses (MCAv) were similar between protocols (P = 0.41) due to increased cerebrovascular conductance index (CVCi) during hypoxia (main effect, P = 0.04). Low frequency MAP (at −45 mmHg: 17 ± 5 vs. 0 ± 5 mmHg2, P = 0.01) and MCAv (at −45 mmHg: 4 ± 2 vs. −1 ± 1 cm·s−2, P = 0.04) spectral power density, as well as low frequency MAP‐mean MCAv transfer function gain (at −30 mmHg: 0.09 ± 0.06 vs. −0.07 ± 0.06 cm·s−1·mmHg−1, P = 0.04) increased more during hypoxia versus normoxia. Contrary to our hypothesis, these findings support the notion that cerebral blood flow control is not impaired during exposure to acute hypoxia and progressive central hypovolemia despite lower MAP as a result of compensated increases in cerebral conductance and flow variability.

Cerebral blood flow velocity during simultaneous changes in mean arterial pressure and cardiac output in healthy volunteers

“…Also, while controlling for the effect of PaCO 2 , they found an effect of cardiac output on CBF. A recent study reported stable PaCO 2 in the LBNP model (van Helmond et al 2018 ). As in other studies, we found a reduction in ETCO 2 with increasing hypovolemia.…”

“…However, this may only reflect the methodology used as there is little evidence for these being different physiological entities (Willie et al 2014). Also, averaging values over a period of 15-30 s to eliminate the fluctuations caused by respiration is common (Kaur et al 2018;Serrador et al 2006;Ogoh et al 2015;Washio et al 2018;Tymko et al 2016).…”

“…However, there is a convincing amount of evidence pointing to a significant effect of cardiac output on CBF, both in disease and in health (Neumann et al 2019). In healthy volunteers, several studies have reported reduced cerebral blood velocity with reduced cardiac output during simulated hypovolemia such as lower body negative pressure (LBNP) (Zhang and Levine 2007;Tymko et al 2016;Levine et al 1994;Ogoh et al 2005). There seems to be an effect of cardiac output independent of MAP (Ogoh et al 2005;Meng et al 2015), and the notion of strict autoregulation has largely been abandoned (Willie et al 2014).…”

An assessment of hypercapnia-induced elevations in regional cerebral perfusion during combined orthostatic and heat stresses

“…Recent findings raise a question about the reliability of transcranial Doppler-derived indices of CBF because the diameter of MCA can change with substantial changes in PaCO 2 [ 24 , 25 ]. Also, van Helmond indicated that MCA vel during combined stresses, such as LBNP under hypoxia, might underestimate CBF because these stresses might change MCA diameter [ 26 ]. Therefore, the present protocol evaluated cerebral perfusion via volumetric changes in flow from regions perfused by both the ICA and VA, culminating in the observation that blood flows to both regions decreased below the respective normothermic baselines at the end of LBNP regardless of inhaled gas.…”

Investigating cerebral blood flow control to save the newborn brain

“…We found that both static and dynamic measures of cerebral blood flow are controlled just up until the point that adequate cerebral oxygenation can no longer be maintained due to profound hypovolaemia (van Helmond et al . ). Measurements of dynamic cerebral blood flow control demonstrated increased correlation between cerebral blood flow and blood pressure.…”