Description: Mitochondria-derived danger-associated molecular patterns (DAMPs) play important roles in sterile inflammation after acute injuries. This study was designed to test the hypothesis that 17β-estradiol protects the heart via suppressing myocardial mitochondrial DAMPs after burn injury using an animal model. Sprague-Dawley rats were given a third-degree scald burn comprising 40% total body surface area (TBSA). 17β-Estradiol, 0.5 mg/kg, or control vehicle was administered subcutaneously 15 min following burn. The heart was harvested 24 h postburn. Estradiol showed significant inhibition on the productivity of H 2 O 2 and oxidation of lipid molecules in the mitochondria. Estradiol increased mitochondrial antioxidant defense via enhancing the activities and expression of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Estradiol also protected mitochondrial respiratory function and structural integrity. In parallel, estradiol remarkably decreased burn-induced release of mitochondrial cytochrome c and mitochondrial DNA (mtDNA) into cytoplasm. Further, estradiol inhibited myocardial apoptosis, shown by its suppression on DNA laddering and downregulation of caspase 1 and caspase 3. Estradiol's anti-inflammatory effect was demonstrated by reduction in systemic and cardiac cytokines (TNF-α, IL-1β, and IL-6), decrease in NF-B activation, and attenuation of the expression of inflammasome component ASC in the heart of burned rats. Estradiol-provided cardiac protection was shown by reduction in myocardial injury marker troponin-I, amendment of heart morphology, and improvement of cardiac contractility after burn injury. Together, these data suggest that postburn administration of 17β-estradiol protects the heart via an effective control over the generation of mitochondrial DAMPs (mtROS, cytochrome c , and mtDNA) that incite cardiac apoptosis and inflammation.

Description: This study aimed to develop and validate a method to measure bolus flow time (BFT) through the esophagogastric junction (EGJ) using a high-resolution impedance-manometry (HRIM) sleeve. Ten healthy subjects were studied with concurrent HRIM and videofluoroscopy; another 15 controls were studied with HRIM alone. HRIM studies were performed using a 4.2-mm-outer diameter assembly with 36 pressure sensors at 1-cm intervals and 18 impedance segments at 2-cm intervals (Given Imaging, Los Angeles, CA). HRIM and fluoroscopic data from four barium swallows, two in the supine and two in the upright position, were analyzed to create a customized MATLAB program to calculate BFT using a HRIM sleeve comprising three sensors positioned at the crural diaphragm. Bolus transit through the EGJ measured during blinded review of fluoroscopy was almost identical to BFT calculated with the HRIM sleeve, with the nadir impedance deflection point used as the signature of bolus presence. Good correlation existed between videofluoroscopy for measurement of upper sphincter relaxation to beginning of flow [ R = 0.97, P 〈 0.001 (supine) and R = 0.77, P 〈 0.01 (upright)] and time to end of flow [ R = 0.95, P 〈 0.001 (supine) and R = 0.82, P 〈 0.01 (upright)]. The medians and interquartile ranges (IQR) of flow time though the EGJ in 15 healthy subjects calculated using the virtual sleeve were 3.5 s (IQR 2.3–3.9 s) in the supine position and 3.2 s (IQR 2.3–3.6 s) in the upright position. BFT is a new metric that provides important information about bolus transit through the EGJ. An assessment of BFT will determine when the EGJ is open and will also provide a useful method to accurately assess trans-EGJ pressure gradients during flow.