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.

Molecular Response of Rabbit Menisci to Surgically Induced Hemarthrosis and a Single Intra-Articular Dexamethasone Treatment.

Anterior cruciate ligament reconstructive surgery can restore biomechanical stability, however, such surgery cannot reliably prevent the onset of post-traumatic osteoarthritis. The aim of this study was to elucidate the molecular response that occurs within the menisci following a surgical injury that allows bleeding into the joint space, and then to investigate the effect of dexamethasone (DEX) on this molecular response. Cell viability studies following acute controlled exposure to blood and blood plus DEX were also conducted. Forty-eight New Zealand white rabbits were randomly allocated into control, sham, surgical, and surgical + DEX groups (each group n = 6). Animals were sacrificed at 48 h and 9 weeks, and menisci were harvested. The messenger RNA (mRNA) expression levels for key inflammatory, and degradative proteins, as well as mRNA levels for autophagy pathway molecules were quantified, and statistically significant changes were described. Meniscal cell viability was calculated by incubating groups of medial and lateral menisci in autologous blood, or autologous blood plus DEX for 48 h (each group n = 4; total of eight medial and eight lateral menisci), and then conducting a histological live/dead assay. Results indicated a significant reduction in only medial meniscal cell viability when the tissue was exposed to blood in combination with DEX. A single administration of DEX following surgery significantly suppresses the elevated molecular expression for key inflammatory and degradative markers within menisci at 48 h and 9 weeks post-surgery. In vitro, autologous blood did not affect cell viability, but addition of DEX uniquely impacted the medial menisci. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2043-2052, 2019.