Assessing the sensitivity of multi-distance hsNIRS for measuring changes in oxCCO in the brain

A hybrid multi-distance hyperspectral near-infrared spectroscopy (hsNIRS) and diffuse correlation spectroscopy (DCS) optical system was used to test transient changes in cytochrome c oxidase (oxCCO) in the brain during carotid compressions (CC) and hypercapnia

Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress

© 2017 the American Physiological Society. This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (age 33 ± 12 yr), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during 1) functional residual capacity apnea (FRCApnea) and 2) continued RBR. Data from RBR were analyzed at matched (i.e., to FRCApnea) hemoglobin saturation (HbSat) levels (RBRMatched) or more severe levels (RBREnd). A third protocol compared alternating periods (30 s) of FRC and RBR (FRC-RBRALT). Subjects continued each protocol until 85% volitional tolerance. AP patterns in MSNA (i.e., providing the true neural content of each sympathetic burst) were studied using wavelet-based methodology. First, for similar levels of chemoreflex stress (both HbSat: 71 ± 6%; P = NS), RBRMatched was associated with reduced AP frequency and APs per burst compared with FRCApnea (both P _ 0.001). When APs were binned according to peak-to-peak amplitude (i.e., into clusters), total AP clusters increased during FRCApnea (+10 ± 2; P \u3c 0.001) but not during RBRMatched (+1 ± 2; P = NS). Second, despite more severe chemoreflex stress during RBREnd (Hb-Sat: 56 ± 13 vs. 71 ± 6%; P = 0.001), RBREnd was associated with a restrained increase in the APs per burst (FRCApnea: +18 ± 7; RBREnd: +11 ± 5) and total AP clusters (FRCApnea: +10 ± 2; RBREnd: +6 ± 4) (both P \u3c 0.01). During FRC-RBRALT, all periods of FRC elicited sympathetic AP recruitment (all P \u3c 0.001), whereas all periods of RBR were associated with complete withdrawal of AP recruitment (all P = NS). Presently, we demonstrate that ventilation per se restrains and/or inhibits sympathetic axonal recruitment during high, and even extreme, chemoreflex stress. NEW & NOTEWORTHY The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress

Rapid changes in cerebrovascular compliance during vasovagal syncope.

PURPOSE: The compensatory mechanisms supporting cerebral perfusion throughout head-up tilt (HUT) in patients with vasovagal syncope (VVS) remain unclear. We tested the hypothesis that increased cerebrovascular compliance (Ci) and decreased cerebrovascular resistance (CVR) support cerebral blood velocity (CBV) during pre-syncope in VVS. METHODS: Finger arterial blood pressure (ABP) and right middle cerebral artery blood velocity (CBV) were recorded in 15 individuals diagnosed with VVS (n = 11 female, mean age: 40 ± 16 years, mean body mass index: 24.9 ± 4.0 kg/m RESULTS: Diastolic ABP, systolic ABP, mean ABP (72 ± 11 to 51 ± 12 mmHg), and CVR decreased progressively during presyncope (all P ≤ 0.04). As expected, systolic CBV was sustained (all P ≥ 0.29) while diastolic and mean CBV (51 ± 13 to 38 ± 13 mmHg) fell during presyncope (all P ≤ 0.04). Both Ci and Pi increased during presyncope (128 ± 97 and 60 ± 41%, respectively; all P ≤ 0.049) and were positively correlated (R CONCLUSIONS: These data provide evidence that Ci increases during presyncope in patients with VVS and is likely involved in the maintenance of systolic CBV during a fall in diastolic CBV. However, this regulation is not sufficient to preserve CBV in the presence of such extreme and progressive reductions in ABP

Reactivity of larger intracranial arteries using 7 T MRI in young adults

© The Author(s) 2018. The larger intracranial conduit vessels contribute to the total cerebral vascular resistance, and understanding their vasoreactivity to physiological stimuli is required when attempting to understand regional brain perfusion. Reactivity of the larger cerebral conduit arteries remains understudied due to a need for improved imaging methods to simultaneously assess these vessels in a single stimulus. We characterized reactivity of basal intracranial conduit arteries (basilar, right and left posterior, middle and anterior cerebral arteries) and the right and left internal carotid arteries, to manipulations in end-tidal CO2 (PetCO2). Cross-sectional area changes (%CSA) were evaluated from high-resolution (0.5 mm isotropic) images collected at 7 T using a T1-weighted 3D SPACE pulse sequence, providing high contrast between vessel lumen and surrounding tissue. Cerebrovascular reactivity was calculated as %CSA/ΔPetCO2 in eight healthy individuals (18–23 years) during normocapnia (41 ± 4 mmHg), hypercapnia (48 ± 4 mmHg; breathing 5% CO2, balance oxygen), and hypocapnia (31 ± 8 mmHg; via hyperventilation). Reactivity to hypercapnia ranged from 0.8%/mmHg in the right internal carotid artery to 2.7%/mmHg in the left anterior cerebral artery. During hypocapnia, vasoconstriction ranged from 0.9%/mmHg in the basilar artery to 2.6%/mmHg in the right posterior cerebral artery. Heterogeneous cerebrovascular reactivity to hypercapnia and hypocapnia was characterized across basal intracranial conduit and internal carotid arteries

Assessing the Sensitivity of Multi-Distance Hyperspectral NIRS to Changes in the Oxidation State of Cytochrome C Oxidase in the Brain

Near-infrared spectroscopy (NIRS) measurements of tissue oxygen saturation (StO2) are frequently used during vascular and cardiac surgeries as a non-invasive means of assessing brain health; however, signal contamination from extracerebral tissues remains a concern. As an alternative, hyperspectral (hs)NIRS can be used to measure changes in the oxidation state of cytochrome c oxidase (ΔoxCCO), which provides greater sensitivity to the brain given its higher mitochondrial concentration versus the scalp. The purpose of this study was to evaluate the depth sensitivity of the oxCCO signal to changes occurring in the brain and extracerebral tissue components. The oxCCO assessment was conducted using multi-distance hsNIRS (source-detector separations = 1 and 3 cm), and metabolic changes were compared to changes in StO2. Ten participants were monitored using an in-house system combining hsNIRS and diffuse correlation spectroscopy (DCS). Data were acquired during carotid compression (CC) to reduce blood flow and hypercapnia to increase flow. Reducing blood flow by CC resulted in a significant decrease in oxCCO measured at rSD = 3 cm but not at 1 cm. In contrast, significant changes in StO2 were found at both distances. Hypercapnia caused significant increases in StO2 and oxCCO at rSD = 3 cm, but not at 1 cm. Extracerebral contamination resulted in elevated StO2 but not oxCCO after hypercapnia, which was significantly reduced by applying regression analysis. This study demonstrated that oxCCO was less sensitive to extracerebral signals than StO2

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids