Respiratory variability of sinus node activation in humans: insights from ultra-high-density mapping.

PURPOSE: Experimental data suggest that shifts in the site of origin of the sinus node (SN) correlate with changes in heart rate and P wave morphology. The direct visualization of the effect of respiration on SN electrical activation has not yet been reported in humans. We aimed to measure the respiratory shifting of the SN activation using ultra-high-density mapping. METHODS: Sequential right atrial (RA) activation mapping during sinus rhythm (SR) was performed. Three maps were acquired for each patient: basal end-expiratory (Ex), end-inspiratory (Ins), and end-expiratory under isoproterenol (Iso). The earliest activation site (EAS) was defined as the earliest unipolar electrograms (EGM) with a QS pattern and was localized with respect to the ostium of the superior vena cava (SVC; negative values if EAS inside the SVC). RESULTS: In 20 patients, 49 maps in SR were acquired (20 Ex, 19 Ins, and 10 Iso). Expiratory (944 ± 227 ms) and inspiratory (946 ± 227 ms) SR cycle lengths were similar, but shortened under isoproterenol (752 ± 302 ms). Activation was unicentric in 33 maps and multicentric in 16: 4 during Ins, 10 during Ex, and 2 Iso. EAS location was significantly more cranial in expiration than in inspiration (0.27 ± 12.1 vs 5 ± 11.51 mm, p = 0.01). Iso infusion tends to induce a supplemental cranial shift (-4.07 ± 15.83 vs 0.27 ± 12.7 mm, p = 0.21). EAS were found in SVC in 22.7% of maps (30% Ex, 21% Ins, and 8% Iso). CONCLUSION: Inspiration induces a significant caudal shift of the earliest sinus activation. In one-third of the cases, sinus rhythm earliest activation is inside the SVC.

Synthesis, molecular properties and comparative docking and QSAR of new 2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetic acid derivatives as possible anticancer agents.

Novel coumarin amino acid derivatives were synthesized. The structure of synthesized compounds has established on basis of different spectral data. The optimization geometry, frontier molecular orbitals (FMOs), thermodynamic parameters and chemical reactivity, were discussed using DFT\B3LYP by 6-311G* basis set, to identify a clear view for inter and intramolecular interaction of tested compounds. The molecular electrostatic potential (MEP) has plotted to investigate a recognition manner of synthesized compounds upon COX-2 receptor. All tested compounds showed a promising (NLOs) nonlinear optical properties. Bond dissociation energy (BDE) has studied to investigate a potency of these molecules against autoxidation mechanism Polynomial molecular docking logarithms have performed into the COX-2 active site for tested compounds. The docking protocol that has low RMSD has selected for discussion the binding affinity. The compounds with a high docking score 3,4,6-8,10 and 11 were selected for additional study against ADMET insilico, which showed that these compounds are a good oral bioavailability without observed carcinogenesis affect. The compounds (3,4,6-8,10 and 11) which that passed through docking and ADMET profile have examined their potency against (MCF-7) breast cancer cell in vitro. The compound 7 showed a highest potency against MCF-7 with IC50 value 0.39 µM. The QSAR model has created to discover the structural necessity inhibition of MCF-7. The derived QSAR model has a statistically significant with a good predictive power.