Hydralazine inhibits ventricular tachyarrhythmias in an acquired long QT rabbit model

Background: Some cardioactive vasodilating agents inhibit ventricular tachyarrhythmias (VT) associated with acquired long QT syndrome (LQT). We tested whether a vasodilator without direct cardiac effect can eliminate abnormal repolarization-related VT. Methods: The effect of hydralazine on the occurrence of VT was assessed in a methoxamine-sensitized rabbit model of acquired LQT. To verify that VTs in this animal model are triggered by early afterdepolarization (EAD), monophasic action potential (MAP) on the left ventricular surface was recorded in open-chest rabbits. Results: In control rabbits, combined administration of methoxamine and nifekalant frequently induced VTs (16/20, 80%). In contrast, VT occurred only in 2 out of 14 rabbits treated with hydralazine (14.3%, P<0.0001 vs. control). After the treatment, blood pressure was lower in the hydralazine group than in the control group (systolic pressure, 146±19 vs. 165±16 mmHg, P<0.0001; diastolic pressure, 54±10 vs. 101±11 mmHg, P<0.0001). EAD-like hump was less frequently detected in hydralazine-treated rabbits (2/10) than in saline-treated rabbits (9/10, P<0.005). Presence of a hump was significantly related to the appearance of VTs (P<0.05). Conclusion: Hydralazine inhibited VT in a rabbit LQT model. Vasodilation may have a therapeutic effect on abnormal repolarization-related VT

Effect of statins on the serum soluble form of receptor for advanced glycation end-products and its association with coronary atherosclerosis in patients with angina pectoris

Background: Advanced glycation end-products (AGEs) and their receptor (RAGE) play an important role in the pathogenesis of diabetic vascular complications. Recently, soluble form of RAGE (sRAGE) has been identified in mice and humans. Statins have been reported to increase serum sRAGE levels. However, whether modulation of circulating sRAGE levels has a beneficial effect on the progression of atherosclerosis is unknown. Methods: We reviewed 91 patients who had undergone percutaneous coronary intervention for angina pectoris. Coronary atherosclerosis in non-culprit lesions in the target vessel was evaluated, using virtual histology intravascular ultrasound, and serum levels of AGEs and sRAGE were measured, at baseline and after 8 months of statin therapy. Results: Statins had no effects on serum AGEs levels; however, serum levels of sRAGE were significantly higher at the 8-month follow-up. A significant decrease in external elastic membrane (EEM) volume (−1.6%, p = 0.005) was observed, whereas a decrease in plaque volume did not reach statistical significance (−1.9%, p = 0.16). Univariate regression analyses showed that the percentage changes in serum sRAGE were negatively correlated with those in EEM volume (r = −0.198, p = 0.06) and plaque volume (r = −0.247, p = 0.02). Multivariate regression analysis showed that an increase in serum sRAGE level was an independent predictor of atheroma regression after statin therapy (β = −0.290, p = 0.006). Conclusions: Statin therapy increased serum sRAGE levels, and this increase was associated with negative vessel remodeling and atheroma regression in the coronary artery

Anomalous signal from S atoms in protein crystallographic data from an X-ray free-electron laser

X-ray free-electron lasers (FELs) enable crystallographic data collection using extremely bright femtosecond pulses from microscopic crystals beyond the limitations of conventional radiation damage. This diffraction-before-destruction approach requires a new crystal for each FEL shot and, since the crystals cannot be rotated during the X-ray pulse, data collection requires averaging over many different crystals and a Monte Carlo integration of the diffraction intensities, making the accurate determination of structure factors challenging. To investigate whether sufficient accuracy can be attained for the measurement of anomalous signal, a large data set was collected from lysozyme microcrystals at the newly established `multi-purpose spectroscopy/imaging instrument' of the SPring-8 Ångstrom Compact Free-Electron Laser (SACLA) at RIKEN Harima. Anomalous difference density maps calculated from these data demonstrate that serial femtosecond crystallography using a free-electron laser is sufficiently accurate to measure even the very weak anomalous signal of naturally occurring S atoms in a protein at a photon energy of 7.3 keV