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.

Regional differences in cerebrovascular reactivity in response to acute isocapnic hypoxia in healthy humans: Methodological considerations.

The cerebrovasculature responds to blood gas challenges. Regional differences (anterior vs. posterior) in cerebrovascular responses to increases in CO2 have been extensively studied. However, regional cerebrovascular reactivity (CVR) responses to low O2 (hypoxia) are equivocal, likely due to differences in analysis. We assessed the effects of acute isocapnic hypoxia on regional CVR comparing absolute and relative (%-change) responses in the middle cerebral artery (MCA) and posterior cerebral artery (PCA). We instrumented 14 healthy participants with a transcranial Doppler ultrasound (cerebral blood velocity), finometer (beat-by-beat blood pressure), dual gas analyzer (end-tidal CO2 and O2), and utilized a dynamic end-tidal forcing system to elicit a single 5-min bout of isocapnic hypoxia (∼45 Torr PETO2, ∼80 % SpO2). During exposure to acute hypoxia, absolute responses were larger in the anterior compared to posterior cerebral circulation (P < 0.001), but were not different when comparing relative responses (P = 0.45). Consistent reporting of CVR to hypoxia will aid understanding normative responses, particularly in assessing populations with impaired cerebrovascular function.

Cardiorespiratory plasticity in humans following two patterns of acute intermittent hypoxia.

NEW FINDINGS: What is the central question of this study? Do cardiorespiratory experience-dependent effects (EDEs) differ between two different stimulus durations of acute isocapnic intermittent hypoxia (IHx; 5-min vs. 90-s cycles between hypoxia and normoxia)? What is the main finding and its importance? There was long-term facilitation in ventilation and blood pressure in both IHx protocols, but there was no evidence of progressive augmentation or post-hypoxia frequency decline. Not all EDEs described in animal models translate to acute isocapnic IHx responses in humans, and cardiorespiratory responses to 5-min versus 90-s on/off IHx protocols are largely similar. ABSTRACT: Peripheral respiratory chemoreceptors monitor breath-by-breath changes in arterial CO2 and O2 , and mediate ventilatory changes to maintain homeostasis. Intermittent hypoxia (IHx) elicits hypoxic ventilatory responses, with well-described experience-dependent effects (EDEs), derived mostly from animal work involving intermittent 5-min cycles of hypoxia and normoxia. These EDEs include post-hypoxia frequency decline (PHxFD), progressive augmentation (PA) and long-term facilitation (LTF). Comparisons of these EDEs between animal models and humans using similar IHx protocols are lacking. In addition, it is unknown whether shorter bouts of hypoxia, which may be more relevant to clinical conditions, elicit EDEs of similar magnitudes in humans. Respiratory (frequency, tidal volume and minute ventilation ( V̇I ) and cardiovascular (heart rate and mean arterial pressure (MAP)) variables were measured during and following two patterns of acute isocapnic IHx in 14 healthy human participants (four female): (1) 5 × 5 min and (2) 5 × 90 s on/off hypoxia. Participants' end-tidal PO2 was clamped at 45 Torr during hypoxia and 100 Torr during normoxia. We found that (1) PHxFD and PA were not present in either IHx pattern (P > 0.14), (2) LTF was present in V̇I following both 5-min (P < 0.001) and 90-s isocapnic IHx trials (P < 0.001), and (3) LTF was present in MAP following 5-min isocapnic IHx (P < 0.001), and trended towards significance following 90-s IHx (P = 0.058). We demonstrate that acute isocapnic IHx alone may not elicit all of the EDEs that have been described in animal models. Additionally, ventilatory LTF occurred regardless of the length of hypoxia-normoxia cycles.