4-Trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine acid exerts its effects on the prevention, post-therapeutic and prolongation of the thrombolytic window in ischemia-reperfusion rats through multiple mechanisms of action.

Ischemic stroke is one of the leading causes of death and disability worldwide. The severe sequelae caused by ischemic thrombolysis and the narrow time window are now the main clinical challenges. Our previous study has reported 4-Trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine Acid (AE-18) was a promising candidate for Parkinson's Disease. In this study, the preventive and therapeutic effects of AE-18 on focal cerebral ischemia-reperfusion injury and the mechanisms are explored. In oxygen glucose deprivation/reoxygenation (OGD/R)-induced well-differentiated PC12 cells model, AE-18 (10 or 20 µM) can significantly reduce nerve damage when administered before or after molding. In middle cerebral artery occlusion-reperfusion (MCAO/R) rat model, pre-modelling, or post-modelling administration of AE-18 (5 or 10 mg/kg) was effective in reducing neurological damage, decreasing infarct volume and improving motor disturbances. In addition, AE-18 (5 mg/kg) given by intravenous injection immediately after occlusion significantly reduce the infarct volume caused by reperfusion for different durations, indicating that AE-18 could extend the time window of thrombolytic therapy. Further studies demonstrate that AE-18 exerts the effects in the prevention, treatment, and prolongation of the time window of cerebral ischemic injury mainly through inhibiting excitotoxicity and improving BBB permeability, VEGF and BDNF. These results suggest that AE-18 is a good candidate for the treatment of ischemic stroke.

Validation of methods for effective orifice area measurement of prosthetic valves by two-dimensional and Doppler echocardiography following transcatheter self-expanding aortic valve implantation.

BACKGROUND: The effective orifice area (EOA) is utilized to characterize the hemodynamic performance of the transcatheter heart valve (THV). However, there is no consensus on EOA measurement of self-expanding THV. We aimed to compare two echocardiographic methods for EOA measurement following transcatheter self-expanding aortic valve implantation. METHODS: EOA was calculated according to the continuity equation. Two methods were constructed. In Method 1 and Method 2, the left ventricular outflow tract diameter (LVOTd) was measured at the entry of the prosthesis (from trailing-to-leading edge) and proximal to the prosthetic valve leaflets (from trailing-to- leading edge), respectively. The velocity-time integral (VTI) of the LVOT (VTILVOT) was recorded by pulsed-wave Doppler (PW) from apical windows. The region of the PW sampling should match that of the LVOTd measurement with precise localization. The mean transvalvular pressure gradient (MG) and VTI of THV was measured by Continuous wave Doppler. RESULTS: A total of 113 consecutive patients were recruited. The mean age was 77.2 ± 5.5 years, and 72 patients (63.7%) were male. EOA1 with the use of Method 1 was larger than EOA2 (1.56 ± 0.39 cm2 vs. 1.48 ± 0.41 cm2, P = 0.001). MG correlated better with the indexed EOA1 (EOAI1) (r = -0.701, P < 0.001) than EOAI2 (r = -0.645, P < 0.001). According to EOAI (EOAI ≤ 0.65 cm2/m2, respectively), the proportion of sever prosthesis-patient mismatch with the use of EOA1 was lower than EOA2 (12.4% vs. 21.2%, P < 0.05). Compared with EOA2, EOA1 had lower interobserver and intra-observer variability (intra: 0.5% ± 17% vs. 3.8% ± 22%, P < 0.001; inter: 1.0% ± 9% vs. 3.5% ± 11%, P < 0.001). CONCLUSIONS: For transcatheter self-expanding valve EOA measurement, LVOTd should be measured in the entry of the prosthesis stent (from trailing-to-leading edge), and VTILVOT should match that of the LVOTd measurement with precise localization.