In vitro effects of ATG-Fresenius on immune cell adhesion.

INTRODUCTION: ATG-Fresenius, a purified rabbit polyclonal anti-human T-lymphocyte immunoglobulin is used for induction immunosuppression as well as prevention and treatment of acute rejection episodes among patients receiving solid organ transplants. The aim of this study was to investigate the in vitro activity of ATG-Fresenius upon immune cell adhesion, which may explain its activity to mitigate ischemia-reperfusion injury. MATERIALS AND METHODS: Human vascular endothelial cells (HUVEC) and peripheral blood mononuclear cells (PBMCs) isolated from umbilical vein or peripheral blood were incubated 20 to 24 hours before analysis. HUVEC were incubated with 10 and 100 µg/mL ATG-Fresenius or reference polyclonal rabbit immunoglobulin G. Analysis of immune cell adhesion to endothelial cells was studied in cocultures of PBMCs and adherent HUVEC. Endothelial cell expression of adhesion molecules CD62E and CD54 was determined by flow cytometry. The numbers of T-, B- and natural killer cells attached to HUVEC were also determined by flow cytometry. Groups were compared using one-way analysis of variance. RESULTS: We showed that ATG-Fresenius binds to endothelial cells particularly activated ones expressing increased levels of E-selectin and ICAM-1. The increased binding of ATG-Fresenius to activated endothelial cells was consistent with its known binding to Intercellular Adhesion Molecule 1 (ICAM-1) and selectins. We also showed that ATG-Fresenius inhibited adhesion of prestimulated immune cells to activated endothelium. CONCLUSION: We demonstrated dose-dependent binding of ATG-Fresenius to activated endothelial cells.

MSCT guided sizing of the Edwards Sapien XT TAVI device: impact of different degrees of oversizing on clinical outcome.

AIMS: Prospective data on the usage of 3-dimensional imaging based annulus sizing on the outcome of TAVI is not available yet and there is general uncertainty about the optimal degree of oversizing. In the current study we therefore assessed a 3-D MSCT guided over-sizing approach and evaluated the clinical outcome of different degrees of oversizing. METHODS: TAVI-size-selection was done using systolic MSCT-annulus cross-sectional-area (CSA) measurements in 107 patients with severe aortic stenosis with the goal to oversize the 3rd generation balloon expandable Edwards Sapien XT (ESTV) device in relation to the native aortic annulus CSA. RESULTS: Among different degrees of oversizing there were no differences in the occurrence of stroke, myocardial infarction and death. No aortic injuries were observed. The overall rate of >mild postprocedural aortic regurgitation (PAR) was 7.6%. Increasing oversizing ratios are associated with lower rates of >mild PAR (r = -0.236, p<0.02) with the lowest rate of >mild PAR in patients with area based oversizing ratios >25% and the highest rate in patients with oversizing ratios <15% (0% vs. 15.8%, p<0.02). The rate of postprocedural permanent pacemakers tended to be lower in patients with <15% oversizing compared to those with >25% oversizing (5.3 vs. 16.7%, p<0.23). CONCLUSIONS: MSCT guided ESTV-device sizing is safe and is associated with significantly lower than previously reported rates for PAR. A device/annulus oversizing ratio of 15-25% based on area and 7-12% based on mean diameter appears to provide the best risk-benefit ratio in terms of PAR reduction and conduction disorders.

[Aortic valve stenosis: transcatheter aortic valve implantation (TAVI) ­ transarterial or transapical approach]. / Aortenklappenstenosen: Kathetergestützte Aortenklappenimplantation (TAVI) ­ transarterieller oder transapikaler Zugang.

The calcified aortic stenosis is the dominating valve disease. Patients affected are most common elderly people in the 8 (th) or 9 (th) decade of their life who often show associated comorbidities like reduced left ventricular function, impaired renal function, pulmonary hypertension, and further diseases (Diabetes mellitus, stroke, COPD). In many cases perioperative morbidity and mortality are too high for surgical valve replacement and up to 30 % of patients are rejected. Nevertheless, prognosis of aortic stenosis is worse if the typical symptoms like dyspnea on exertion, syncope, and angina occur. The transcatheter aortic valve implantation is a new method treating this particular group of patients. The aortic valve bioprothesis consists of a balloon-expandable stent or a self-expandable frame, in which a valve of bovine or porcine pericardium is incorporated. The implantation is performed by retrograde access via the femoral or subclavian artery; the balloon-expandable prosthesis can also be implanted by transapical approach. Recently, the PARTNER trial and other studies demonstrate a high implantation success rate and better survival in comparison to standard therapy but exhibit also cerebral vascular and peripheral vascular complications. A further reduction of the available delivery systems and new types of valves which are under experimental tests and clinical evaluation contribute to this development.