The effects of acute incremental hypocapnia on the magnitude of neurovascular coupling in healthy participants.

The high metabolic demand of cerebral tissue requires that local perfusion is tightly coupled with local metabolic rate (neurovascular coupling; NVC). During chronic altitude exposure, where individuals are exposed to the antagonistic cerebrovascular effects of hypoxia and hypocapnia, pH is maintained through renal compensation and NVC remains stable. However, the potential independent effect of acute hypocapnia and respiratory alkalosis on NVC remains to be determined. We hypothesized that acute steady-state hypocapnia via voluntary hyperventilation would attenuate the magnitude of NVC. We recruited 17 healthy participants and insonated the posterior cerebral artery (PCA) with transcranial Doppler ultrasound. NVC was elicited using a standardized strobe light stimulus (6 Hz; 5 × 30 s on/off) where absolute delta responses from baseline (BL) in peak, mean, and total area under the curve (tAUC) were quantified. From a BL end-tidal (PET )CO2  level of 36.7 ± 3.2 Torr, participants were coached to hyperventilate to reach steady-state hypocapnic steps of Δ-5 Torr (31.6 ± 3.9) and Δ-10 Torr (26.0 ± 4.0; p < 0.001), which were maintained during the presentation of the visual stimuli. We observed a small but significant reduction in NVC peak (ΔPCAv) from BL during controlled hypocapnia at both Δ-5 (-1.58 cm/s) and Δ-10 (-1.37 cm/s), but no significant decrease in mean or tAUC NVC response was observed. These data demonstrate that acute respiratory alkalosis attenuates peak NVC magnitude at Δ-5 and Δ-10 Torr PET CO2 , equally. Although peak NVC magnitude was mildly attenuated, our data illustrate that mean and tAUC NVC are remarkably stable during acute respiratory alkalosis, suggesting multiple mechanisms underlying NVC.

Bader TJ ，Leacy JK ，Keough JRG ，Ciorogariu-Ivan AM ，Donald JR ，Marullo AL ，O'Halloran KD ，Jendzjowsky NG ，Wilson RJA ，Day TA ... -  《Physiological Reports》

Neurovascular Coupling Remains Intact During Incremental Ascent to High Altitude (4240 m) in Acclimatized Healthy Volunteers.

Leacy JK ，Zouboules SM ，Mann CR ，Peltonen JDB ，Saran G ，Nysten CE ，Nysten HE ，Brutsaert TD ，O'Halloran KD ，Sherpa MT ，Day TA ... -  《Frontiers in Physiology》

The effect of CO(2) on the age dependence of neurovascular coupling.

Davies A ，Gurung D ，Ladthavorlaphatt K ，Mankoo A ，Panerai RB ，Robinson TG ，Minhas JS ，Beishon LC ... -  《-》

Alterations in arterial CO(2) rather than pH affect the kinetics of neurovascular coupling in humans.

We investigated the influence of arterial PCO2 ( PaCO2 ) with and without acute experimental metabolic alkalosis on neurovascular coupling (NVC). We assessed stepwise iso-oxic alterations in PaCO2 prior to and following intravenous NaHCO3 to acutely elevate arterial pH and [HCO3- ]. The NVC response was not altered following NaHCO3 between stepwise PaCO2 stages; therefore, NVC is acutely mediated by PaCO2 rather than the prevailing arterial [H+ ]/pH. The NVC response was attenuated by 27-38% with -10 mmHg PaCO2 and the absolute peak change was reduced by -19% with +10 mmHg PaCO2 irrespective of acutely elevated arterial pH/[HCO3- ]. The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24 ± 5 vs. 7 ± 5 s, respectively) likely indicating an influence of resting cerebrovascular tone on NVC responsiveness. Elevations in cerebral metabolism necessitate appropriate coordinated and localized increases in cerebral blood flow (i.e. neurovascular coupling; NVC). Recent pre-clinical work indicates that arterial PCO2 ( PaCO2 ) mediates NVC independently of arterial/extracellular pH; this has yet to be experimentally tested in humans. The goal of this study was to investigate the hypotheses that: (1) the NVC response would be unaffected by acute experimentally elevated arterial pH; rather, PaCO2 would regulate any changes in NVC; and (2) stepwise respiratory alkalosis and acidosis would each progressively reduce the NVC response. Ten healthy males completed a standardized visual stimulus-evoked NVC test during matched stepwise iso-oxic alterations in PaCO2 (hypocapnia: -5, -10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following intravenous NaHCO3 (8.4%, 50 mEq/50 ml) that elevated arterial pH (7.406 ± 0.019 vs. 7.457 ± 0.029; P < 0.001) and [HCO3- ] (26.2 ± 1.5 vs. 29.3 ± 0.9 mEq/l; P < 0.001). Although the NVC response was collectively attenuated by 27-38% with -10 mmHg PaCO2 (stage post hoc: all P < 0.05), this response was unaltered following NaHCO3 (all P > 0.05) irrespective of the higher pH (P = 0.002) at each matched stage of PaCO2 (P = 0.417). The absolute peak change was reduced by -19 ± 41% with +10 mmHg PaCO2 irrespective of acutely elevated arterial pH/[HCO3- ] (stage post hoc: P = 0.022). The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24 ± 5 vs. 7 ± 5 s, respectively; stage effect: P < 0.001). Overall, these findings indicate that temporal patterns in NVC are acutely regulated by PaCO2 rather than arterial pH per se in the setting of acute metabolic alkalosis in humans.

Caldwell HG ，Howe CA ，Hoiland RL ，Carr JMJR ，Chalifoux CJ ，Brown CV ，Patrician A ，Tremblay JC ，Panerai RB ，Robinson TG ，Minhas JS ，Ainslie PN ... -  《-》

Neurovascular coupling is not influenced by lower body negative pressure in humans.

Samora M ，Vianna LC ，Carmo JC ，Macedo V ，Dawes M ，Phillips AA ，Paton JFR ，Fisher JP ... -  《-》