No abstract

Lower body negative pressure (LBNP) chambers can be utilized to experimentally‐elicit reductions in blood pressure, cerebral blood flow (CBF) and associated symptoms of presyncope. There is high between‐individual variability in tolerance to LBNP, however the underlying physiological responses affecting tolerance remains unclear. Pulsatility in CBF may affect LBNP tolerance, as more pulsatile flow may protect the delivery of oxygen to cerebral tissues in hypotension. We aimed to assess the pulsatility index (PI) in anterior and posterior cerebral circulations during LBNP in superimposed head‐up tilt (HUT), where gravitational‐induced blood volume re‐distribution augments volume unloading during LBNP. We recruited and included 12 healthy male participants, and instrumented them in a custom‐build integrated 45° HUT‐LBNP chamber. Participants were instrumented for heart rate (HR; ECG), end‐tidal CO2 (PETCO2; mouthpiece and gas analyzer),beat‐by‐beat mean arterial pressure (MAP; finometer), and middle and posterior cerebral artery velocity (MCAv, PCAv; transcranial Doppler ultrasound). All measures were recorded during baseline (BL) and during ‐50 mmHg LBNP exposure up to a maximum of 10‐minutes (600s). Presyncope was defined as a 30% reduction in systolic blood pressure (i.e., investigator stop) or onset subjective symptoms (i.e., participant stop). We quantified all variables as a 30‐sec mean bin during BL and the final 30‐sec of LBNP prior to presyncope. MAP, MCAv and PCAv PI was calculated as systolic‐diastolic/mean. LBNP tolerance time was 480.9±134.3 sec. HR increased from 72.3±10.3 (BL) to 103.0±18.2 bpm (P<0.01) during LBNP, suggesting a baroreflex response, and PETCO2 was reduced from 32.0±2.9 (BL) to 28.7±2.9 Torr (P<0.01) during LBNP, suggesting mild hyperventilation. MAP decreased from 84.8±11.3 (BL) to 76.2±14.7 mmHg (P<0.01) during LBNP, with associated reductions in mean MCAv from 52.1±15.0 to 44.3±14.5 cm/s (P<0.01), and mean PCAv from 35.5±12.6 to 29.0±9.9 cm/s (P<0.01) during LBNP. MAP PI was reduced from 0.76±0.2 to 0.59±0.02 (P<0.01) during LBNP. However, MCAv and PCAv PI were unchanged during LBNP (P=0.6 and P=0.9, respectively). Our results suggest that although MAP and MAP PI were both reduced during LBNP at pre‐syncope, with associated reductions in mean MCAv and PCAv, MCAv and PCAv PI remained stable with LBNP in HUT. These findings suggest that PI in CBF variables at the cardiac frequency are not related to LBNP tolerance in healthy men.

Ventilatory acclimatization (VA) is important to maintain adequate oxygenation with ascent to high altitude (HA). Transient hypoxic ventilatory response tests lack feasibility and fail to capture the integrated steady‐state responses to chronic hypoxic exposure in HA fieldwork. We recently characterized a novel index of steady‐state respiratory chemoreflex drive (SSCD), accounting for integrated contributions from central and peripheral respiratory chemoreceptors during steady‐state breathing at prevailing chemostimuli. Acetazolamide is often utilized during ascent for prevention or treatment of altitude‐related illnesses, eliciting metabolic acidosis and stimulating respiratory chemoreceptors. To determine if SSCD reflects VA during ascent to HA, we characterized SSCD in 25 lowlanders during incremental ascent to 4240 m over 7 days. We subsequently compared two separate subgroups: no acetazolamide (NAz; n = 14) and those taking an oral prophylactic dose of acetazolamide (Az; 125 mg BID; n = 11). At 1130/1400 m (day zero) and 4240 m (day seven), steady‐state measurements of resting ventilation (V̇ I ; L/min), pressure of end‐tidal (P ET )CO 2 (Torr), and peripheral oxygen saturation (SpO 2 ; %) were measured. A stimulus index (SI; P ET CO 2 /SpO 2 ) was calculated, and SSCD was calculated by indexing V̇ I against SI. We found that (a) both V̇ I and SSCD increased with ascent to 4240 m (day seven; V̇ I : +39%, p < 0.0001, Hedges' g = 1.52; SSCD: +56.%, p < 0.0001, Hedges' g = 1.65), (b) and these responses were larger in the Az versus NAz subgroup (V̇ I : p = 0.02, Hedges' g = 1.04; SSCD: p = 0.02, Hedges' g = 1.05). The SSCD metric may have utility in assessing VA during prolonged stays at altitude, providing a feasible alternative to transient chemoreflex tests.