Sex Affects Myocardial Blood Flow and Fatty Acid Substrate Metabolism in Humans with Nonischemic Heart Failure

In animal models of heart failure (HF), myocardial metabolism shifts from the normal preference for high-energy fatty acid (FA) metabolism towards the more efficient fuel, glucose. However, FA (vs. glucose) metabolism generates more ATP/mole; thus FA metabolism may be especially advantageous in HF. Sex modulates myocardial blood flow (MBF) and substrate metabolism in normal humans. Whether sex affects MBF and metabolism in patients with HF is unknown. We studied 19 well-matched men and women with nonischemic HF with similar ejection fractions (all ≤ 35%). MBF and myocardial substrate metabolism were quantified using positron emission tomography. Women had higher MBF (mL/g/min), FA uptake (mL/g/min), utilization (nmol/g/min) (P<0.005, <0.005, <0.05, respectively) and trended towards higher FA oxidation than men (P=0.09). These findings were independent of age, obesity, and insulin resistance. There were no sex-related differences in fasting myocardial glucose uptake or metabolism. In an exploratory analysis of the longitudinal follow-up of these subjects (mean 7 y), we found that 4 men had a major cardiovascular event, while one woman died of non-cardiac causes. Higher MBF related to improved event-free survival (HR=0.31, P=0.02). In sum, in nonischemic HF, women have higher MBF and FA uptake and metabolism than men, and these changes are not due to differences in other variables that can affect myocardial metabolism (e.g., age, obesity, or insulin resistance). Moreover, higher MBF portends a better prognosis. These sex-related differences should be taken into account in the development and targeting of novel agents aimed at modulating in MBF and metabolism in HF

Molecular imaging of hypoxia with radiolabelled agents

Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant progression. This has led to the development of assays for the detection of hypoxia in patients in order to predict outcome and identify patients with a worse prognosis and/or patients that would benefit from appropriate treatments. A variety of invasive and non-invasive approaches have been developed to measure tumour oxygenation including oxygen-sensitive electrodes and hypoxia marker techniques using various labels that can be detected by different methods such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), autoradiography and immunohistochemistry. This review aims to give a detailed overview of non-invasive molecular imaging modalities with radiolabelled PET and SPECT tracers that are available to measure tumour hypoxia

Structural evidence from shock metamorphism in simple and complex impact craters: Linking observations to theory

From the proceedings of the Workshop on Impact Cratering: Bridging the Gap between Modeling and Observations held in February 2003 at the Lunar and Planetary Institute in Houston, Texas.The structure of Canadian impact craters formed in crystalline rocks is analyzed using shock metamorphism and evidence for movement along shear zones. The analysis is based on an interpretation that, beyond the near field region, shock pressure attenuates down axis as P ~ R^(-2), in agreement with nuclear test and computed results, and as P ~ R^(-3) near the surface. In both simple and complex craters, the transient cavity is defined by the limit of fragmentation due to direct and reflected shock waves. The intersection of the transient cavity with hemispheric shock isobars indicates that the transient cavity has a parabolic form. Weakening by dilation during early uplift allows late stage slumping of the walls of simple craters. This is controlled by a spheroidal primary shear of radius rs is approximately equal to 2dt, where dt is the depth of the transient crater due to excavation and initial compression. With increasing crater diameter, the size of the transient cavity decreases relative to the shock imprint, suggesting that fragmentation and excavation is limited by progressively earlier collapse of the margins under gravity. Central peak formation in complex craters may be initiated by relaxation of the shock-compressed central parautochthone, so the primary shear, lubricated by friction melting, meets below the crater floor and drives the continuing upward motion.The Meteoritics & Planetary Science archives are made available by the Meteoritical Society and the University of Arizona Libraries. Contact [email protected] for further information.Migrated from OJS platform February 202