Dose-dependency for nitrite-induced hypoxic vasodilation in the presence and absence of myoglobin (Mb).

<p>(A) Experimental schema. After equilibration, normoxic gassing was either continued or changed to hypoxia (1% O₂). Isolated aortic rings of <i>Mb^+/+</i> and <i>Mb^−/−</i> mice were then pre-constricted using phenylephrine (Phe) and subsequently challenged with cumulating doses of nitrite from physiological to pharmacological levels. Under normoxia, nitrite-vasodilation response were identical in both mouse types (B) leading to similar EC₅₀ levels (C). On the contrary, under hypoxia, nitrite-induced vasodilation was significantly impaired in <i>Mb^−/−</i> (D) with significantly higher resulting EC₅₀ levels (E). All values are means±s.e.m.</p

Endogenous ROS modulate the nitrite-induced hypoxic vasodilation response.

<p>(A) Experimental schema. After an equilibration period, SOD, SOD mimic tempol, catalase and gluthation peroxidase mimic ebselen were added to the organ bath in order to decompose endogenously formed ROS. The nitrite concentration in the organ bath was 300 nM. Vessels were then preconstricted with phenylephrine (Phe). After stabilization of constriction, hypoxic was induced and vasodilation observed for the following 15 min. (B) Graph shows the decrease in intention for the 15 min of hypoxia for controls and treated rings. Incubation of SOD mimic tempol with catalase and with catalase/ebselen significantly increased the vasodilation response at 10 and 15 min (*<i>P</i><0.05, n = 3–5). Values are means±s.e.m.</p

Hypoxia-induced myoglobin desaturation.

<p>Gassing with a 1% oxygen gas mixture leads to shift of the UV vis spectrum from oxygenated myoglobin (oxyMb) to deoxygenated myoglobin (deoxyMb). Figure shows final levels of saturation with a significant reduction under hypoxic gassing (means±s.d).</p

Role of nitrite and reactive oxygen species (ROS) in hypoxic vasodilation – proposed mechanism.

<p>Nitrite derives from NO^• synthesis dietary sources. NO^• to nitrite reactions occur by autoxidation or by reaction with ceruloplasmin (CP). Under hypoxia, nitrite levels in the vessel wall are increased. Nitrite can then be reduced to vasodilatory NO^• particularly by reaction with myoglobin (Mb). ROS modulate this response.</p

Nitrite and nitrate levels in mouse tissue.

<p>Aortic tissue of NMRI wild-types, myoglobin (Mb) deficient mice, C57BL/6 wild-types and endothelial nitric oxide synthase (eNOS) knockout mice was analyzed for (A) nitrite and (B) nitrate levels with no significant difference between the species as a prerequisite for dose-response experiments (n = 5–6, means±s.d.).</p

Cardiac computed tomography-derived epicardial fat volume and attenuation independently distinguish patients with and without myocardial infarction

<div><p>Background and objective</p><p>Epicardial adipose tissue (EAT) volume is associated with coronary plaque burden and adverse events. We aimed to determine, whether CT-derived EAT attenuation in addition to EAT volume distinguishes patients with and without myocardial infarction.</p><p>Methods and results</p><p>In 94 patients with confirmed or suspected coronary artery disease (aged 66.9±14.7years, 61%male) undergoing cardiac CT imaging as part of clinical workup, EAT volume was retrospectively quantified from non-contrast cardiac CT by delineation of the pericardium in axial images. Mean attenuation of all pixels from EAT volume was calculated. Patients with type-I myocardial infarction (n = 28) had higher EAT volume (132.9 ± 111.9ml vs. 109.7 ± 94.6ml, p = 0.07) and CT-attenuation (-86.8 ± 5.8HU vs. -89.0 ± 3.7HU, p = 0.03) than patients without type-I myocardial infarction, while EAT volume and attenuation were only modestly inversely correlated (r = -0.24, p = 0.02). EAT volume increased per standard deviation of age (18.2 [6.2–30.2] ml, p = 0.003), BMI (29.3 [18.4–40.2] ml, p<0.0001), and with presence of diabetes (44.5 [16.7–72.3] ml, p = 0.0002), while attenuation was higher in patients with lipid-lowering therapy (2.34 [0.08–4.61] HU, p = 0.04). In a model containing volume and attenuation, both measures of EAT were independently associated with the occurrence of type-I myocardial infarction (OR [95% CI]: 1.79 [1.10–2.94], p = 0.02 for volume, 2.04 [1.18–3.53], p = 0.01 for attenuation). Effect sizes remained stable for EAT attenuation after adjustment for risk factors (1.44 [0.77–2.68], p = 0.26 for volume; 1.93 [1.11–3.39], p = 0.02 for attenuation).</p><p>Conclusion</p><p>CT-derived EAT attenuation, in addition to volume, distinguishes patients with vs. without myocardial infarction and is increased in patients with lipid-lowering therapy. Our results suggest that assessment of EAT attenuation could render complementary information to EAT volume regarding coronary risk burden.</p></div

EAT volume and attenuation and any as well as type-I myocardial infarction.

<p>Frequencies of any (grey) and type-I myocardial infarction (dashed), stratified by combination of EAT volume and CT-derived attenuation above vs. below median, demonstrating the complementary value of EAT volume and attenuation.</p

Epicardial fat quantification from cardiac CT examination.

<p>The pericardial sac was manually traced in axial images as region of interest (A). Within this region of interest, pixels between -195 and -45 Hounsfield Units were accounted as fat. After 3-dimensional reconstruction, EAT volume was calculated by summation of all pixels accounted as fat (B). EAT attenuation was defined as mean Hounsfield Units of all fat pixels of the EAT volume.</p

Association of EAT volume and CT-attenuation with traditional cardiovascular risk factors in unadjusted and risk factor adjusted linear regression analysis.

<p>Association of EAT volume and CT-attenuation with traditional cardiovascular risk factors in unadjusted and risk factor adjusted linear regression analysis.</p

In more than 40%, intravascular ultrasound (IVUS) leads to a different sizing strategy in aortic stent grafts.

<p>Shown are the distributions for changes in the sizing strategy made by IVUS in Valiant/Relay stent grafts (A) and GORE according to the recommended sizing chart (B). Further subdivision of the increases in stent graft sizes is presented in the smaller, right circles.</p