The Sodium-Glucose Cotransporter-2 Inhibitor Canagliflozin Alleviates Endothelial Dysfunction Following In Vitro Vascular Ischemia/Reperfusion Injury in Rats.

Vascular ischemia/reperfusion injury (IRI) contributes to graft failure and adverse clinical outcomes following coronary artery bypass grafting. Sodium-glucose-cotransporter (SGLT)-2-inhibitors have been shown to protect against myocardial IRI, irrespective of diabetes. We hypothesized that adding canagliflozin (CANA) (an SGLT-2-inhibitor) to saline protects vascular grafts from IRI. Aortic rings from non-diabetic rats were isolated and immediately mounted in organ bath chambers (control, n = 9-10 rats) or underwent cold ischemic preservation in saline, supplemented either with a DMSO vehicle (IR, n = 8-10 rats) or 50µM CANA (IR + CANA, n = 9-11 rats). Vascular function was measured, the expression of 88 genes using PCR-array was analyzed, and feature selection using machine learning was applied. Impaired maximal vasorelaxation to acetylcholine in the IR-group compared to controls was significantly ameliorated by CANA (IR 31.7 ± 3.2% vs. IR + CANA 51.9 ± 2.5%, p < 0.05). IR altered the expression of 17 genes. Ccl2, Ccl3, Ccl4, CxCr4, Fos, Icam1, Il10, Il1a and Il1b have been found to have the highest interaction. Compared to controls, IR significantly upregulated the mRNA expressions of Il1a and Il6, which were reduced by 1.5- and 1.75-fold with CANA, respectively. CANA significantly prevented the upregulation of Cd40, downregulated NoxO1 gene expression, decreased ICAM-1 and nitrotyrosine, and increased PECAM-1 immunoreactivity. CANA alleviates endothelial dysfunction following IRI.

Gibbs energy functions with the vacancy complexes in the Al-Cu binary system.

The Gibbs energy functions of the phases in the Al-Cu binary system are taken from the CALPHAD-type thermodynamic assessment (Witusiewicz et al., 2004; Ansara et al., 1998) [1], [2], where the effect of the monovacancy (Va), divacancy (VaVa) and Va-solute atom pair are taken into account based on the formulation (Abe et al., In press). The divacancy is modeled as an associate, VaVa, in the FCC solid solution. The contributions from the Va-solute pair are included through the ternary excess Gibbs energy term. Using the Gibbs energy functions provided in this data article, the fractions of the monovacancies and divacancies, even in various metastable conditions, can be calculated. Since the Gibbs energy functions and phase descriptions are written in the TDB (Thermodynamic DataBase) format, one can use this file with various thermodynamic software packages, such as OpenCalphad [3] etc.

Vascular reactivity in preeclampsia assessed noninvasively using maternal brachial artery hyperemic response.

OBJECTIVE: To estimate if women with preeclampsia had measurable differences in the brachial artery waveforms after blood flow occlusion. METHODS: In a cross-sectional study, 14 preeclamptic and 28 matched normotensive women were assessed. Hemolysis, elevated liver enzymes, low platelets syndrome patients were excluded. All patients had baseline brachial Doppler flow velocities while resting in the left lateral position and after a 60-second forearm occlusion. Doppler waveforms were analyzed from the brachial artery 30-45 seconds after the release of the blood pressure cuff. We analyzed the classical Doppler waveform parameters of systolic diastolic, mean velocity and pulsatility index, time taken to achieve peak systolic velocity, systolic acceleration time, the percentage of time in each cycle to achieve peak systolic velocity, and systolic acceleration from 3 waveforms. Comparison of the percentage change in each of these parameters between the groups was done using t tests. RESULTS: Before brachial artery occlusion, systolic acceleration time was significantly less in the preeclamptic group (77.5 +/- 14.4 milliseconds versus 93.2 +/- 11.7 milliseconds; (P < .001). After occlusion, the percentage change in the systolic acceleration and systolic acceleration time was increased in the normotensive group (P < .001). CONCLUSION: There was significantly increased impedance to blood flow downstream assessed by Doppler waveform analysis after a period of forearm ischemia (blood pressure occlusion) in the women with preeclampsia. LEVEL OF EVIDENCE: II-1.