Near-infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans

The final steps of the O2 cascade during exercise depend on the product of the microvascular-tointramyocyte PO2 difference and muscle O2 diffusing capacity (DmO2). Non-invasive methods to determine DmO2 in humans are currently unavailable. Muscle oxygen uptake (mVO2) recovery rate constant (k), measured by near-infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by DmO2 when muscle oxygenation is low (kLOW), and hypothesized that: i) k in well-oxygenated muscle (kHIGH) is associated with maximal O2 flux in fiber bundles; and ii) Δk (kHIGH-kLOW) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index (TSI) within a 10% range either below (LOW) or above (HIGH) half-maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7±10.6 pmol·s−1·mg−1 (~5.8 ml·min−1·100g−1). CD ranged 348 to 586 mm-2. kHIGH was greater than kLOW (3.15±0.45 vs 1.56±0.79 min-1, p\u3c0.001). Maximal O2 flux was correlated with kHIGH (r=0.80, p=0.002) but not kLOW (r=-0.10, p=0.755). Δk ranged -0.26 to -2.55 min-1, and correlated with CD (r=- 0.68, p=0.015). mVO2 k reflects muscle oxidative capacity only in well-oxygenated muscle. Δk, the difference in k between well- and poorly-oxygenated muscle, was associated with CD, a mediator of DmO2. Assessment of muscle k and Δk using NIRS provides a non-invasive window on muscle oxidative and O2 diffusing capacity

The impact of training on diagnostic accuracy with computed tomography coronary angiography

The aim of this study is to assess the image quality and diagnostic accuracy of computed tomography (CT) coronary angiography (CTCA) in different hospital settings with the same trained team

Near‐infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans

The final steps of the O2 cascade during exercise depend on the product of the microvascular-to-intramyocyte PO2${P}_{{{\rm{O}}}_{\rm{2}}}$ difference and muscle O2 diffusing capacity ( DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ ). Non-invasive methods to determine DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ in humans are currently unavailable. Muscle oxygen uptake (m V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) recovery rate constant (k), measured by near-infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ when muscle oxygenation is low (kLOW ), and hypothesized that: (i) k in well oxygenated muscle (kHIGH ) is associated with maximal O2 flux in fibre bundles; and (ii) ∆k (kHIGH  - kLOW ) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index within a 10% range either below (LOW) or above (HIGH) half-maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7 ± 10.6 pmol s-1  mg-1 (∼5.8 ml min-1  100 g-1 ). CD ranged 348 to 586 mm-2 . kHIGH was greater than kLOW (3.15 ± 0.45 vs. 1.56 ± 0.79 min-1 , P < 0.001). Maximal O2 flux was correlated with kHIGH (r = 0.80, P = 0.002) but not kLOW (r = -0.10, P = 0.755). Δk ranged -0.26 to -2.55 min-1 , and correlated with CD (r = -0.68, P = 0.015). m V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ k reflects muscle oxidative capacity only in well oxygenated muscle. ∆k, the difference in k between well and poorly oxygenated muscle, was associated with CD, a mediator of DmO2$D{{\rm{m}}}_{{{\rm{O}}}_2}$ . Assessment of muscle k and ∆k using NIRS provides a non-invasive window on muscle oxidative and O2 diffusing capacity. KEY POINTS: We determined post-exercise recovery kinetics of quadriceps muscle oxygen uptake (m V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ ) measured by near-infrared spectroscopy (NIRS) in humans under conditions of both non-limiting (HIGH) and limiting (LOW) O2 availability, for comparison with biopsy variables. The m V̇O2${\dot{V}}_{{{\rm{O}}}_{\rm{2}}}$ recovery rate constant in HIGH O2 availability was hypothesized to reflect muscle oxidative capacity (kHIGH ) and the difference in k between HIGH and LOW O2 availability (∆k) was hypothesized to reflect muscle O2 diffusing capacity. kHIGH was correlated with phosphorylating oxidative capacity of permeabilized muscle fibre bundles (r = 0.80). ∆k was negatively correlated with capillary density (r = -0.68) of biopsy samples. NIRS provides non-invasive means of assessing both muscle oxidative and oxygen diffusing capacity in vivo

Collateral non cardiac findings in clinical routine CT coronary angiography: results from a multi-center registry

PURPOSE: The aim of the study was to evaluate the prevalence of collateral findings detected in computed tomography coronary angiography (CTCA) in a multi-center registry. MATERIALS AND METHODS: We performed a retrospective review of 4303 patients (2719 males, mean age 60.3 \ub1 10.2 years) undergoing 64-slice CTCA for suspected or known coronary artery disease (CAD) at various academic institutions between 01/2006 and 09/2010. Collateral findings were recorded and scored as: non-significant (no signs of relevant pathology, not necessary to be reported), significant (clear signs of pathology, mandatory to be reported), or major (remarkable pathology, mandatory to be reported and further investigated). RESULTS: We detected 6886 non-cardiac findings (1.6 non cardiac finding per patient). Considering all centers, only 865/4303 (20.1 %) patients were completely without any additional finding. Overall, 2095 (30.4 %) non-significant, 4486 (65.2 %) significant, and 305 (4.4 %) major findings were detected. Among major findings, primary lung cancer was reported in 21 cases. In every center, most prevalent significant findings were mediastinal lymph nodes >1 cm. In 256 patients, collateral findings were clinically more relevant than coexisting CAD and justified the symptoms of patients. CONCLUSIONS: The prevalence of significant and major collateral findings in CTCA is high. Radiologists should carefully evaluate the entire scan volume in each patient

Prognostic value of computed tomography coronary angiography in patients with suspected coronary artery disease: a 24-month follow-up study

The aim of this study was to determine the predictive value of 64-slice computed tomography coronary angiography (CTCA) for major cardiac events in patients with suspected coronary artery disease (CAD). A total of 187 consecutive patients (119 men, age 62.5 +/- 10.5 years) without known heart disease underwent single-source 64-slice CTCA (Somatom Sensation 64, Siemens) for clinical suspicion of CAD. Patients underwent follow-up for the occurrence of cardiac death, nonfatal myocardial infarction, unstable angina and cardiac revascularization. In total, 2,822 coronary segments were assessed. Forty-two segments (1.5%) were not assessable because of insufficient image quality. Overall, CTCA revealed absence of CAD in 65 (34.7%) patients, nonobstructive CAD (coronary plaque a parts per thousand currency sign50%) in 87 (46.5%) patients and obstructive CAD (> 50%) in 35 (18.8%) patients. A total of 20 major cardiac events (3 myocardial infarctions, 16 cardiac revascularizations, 1 unstable angina) occurred during a mean follow-up of 24 months. One noncardiac death occurred. Seventeen events occurred in the group of patients with obstructive CAD and three events occurred in the group of nonobstructive CAD. The event rate was 0% among patients with normal coronary arteries at CTCA. CTCA has a 100% negative predictive value for major cardiac events at 24-month follow-up in patients with normal coronary arteries

Reduced Annexin A1 Expression Associates with Disease Severity and Inflammation in Multiple Sclerosis Patients.

Chronic neuroinflammation is a key pathological hallmark of multiple sclerosis (MS) that suggests that resolution of inflammation by specialized proresolving molecules is dysregulated in the disease. Annexin A1 (ANXA1) is a protein induced by glucocorticoids that facilitates resolution of inflammation through several mechanisms that include an inhibition of leukocyte recruitment and activation. In this study, we investigated the ability of ANXA1 to influence T cell effector function in relapsing/remitting MS (RRMS), an autoimmune disease sustained by proinflammatory Th1/Th17 cells. Circulating expression levels of ANXA1 in naive-to-treatment RRMS subjects inversely correlated with disease score and progression. At the cellular level, there was an impaired ANXA1 production by CD4+CD25- conventional T and CD4+RORγt+ T (Th17) cells from RRMS subjects that associated with an increased migratory capacity in an in vitro model of blood brain barrier. Mechanistically, ANXA1 impaired monocyte maturation secondarily to STAT3 hyperactivation and potently reduced T cell activation, proliferation, and glycolysis. Together, these findings identify impaired disease resolution pathways in RRMS caused by dysregulated ANXA1 expression that could represent new potential therapeutic targets in RRMS

Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential

Human CD4(+)CD25(hi)FOXP3(+) regulatory T (Treg) cells are key players in the control of immunological self-tolerance and homeostasis. Here, we report that signals of pseudo-starvation reversed human Treg cell in vitro anergy through an integrated transcriptional response, pertaining to proliferation, metabolism, and transmembrane solute carrier transport. At the molecular level, the Treg cell proliferative response was dependent on the induction of the cystine/ glutamate antiporter solute carrier (SLC)7A11, whose expression was controlled by the nuclear factor erythroid 2-related factor 2 (NRF2). SLC7A11 induction in Treg cells was impaired in subjects with relapsing-remitting multiple sclerosis (RRMS), an autoimmune disorder associated with reduced Treg cell proliferative capacity. Treatment of RRMS subjects with dimethyl fumarate (DMF) rescued SLC7A11 induction and fully recovered Treg cell expansion. These results suggest a previously unrecognized mechanism that may account for the progressive loss of Treg cells in autoimmunity and unveil SLC7A11 as major target for the rescue of Treg cell proliferation