Because of their insufficient biocompatibility and high thrombogenicity, small diameter artificial vascular prostheses still do not show a satisfactory patency rate. In vitro endothelialization of artificial grafts before implantation has been established experimentally years ago, but, this procedure is extremely time consuming and expensive. This study deals with the coating of graft surfaces with capture molecules (aptamers) for circulating endothelial progenitor cells (EPCs), mimicking a prohoming substrate to fish out EPCs from the bloodstream after implantation and to create an autologous functional endothelium. Using the SELEX technology, aptamers with a high affinity to EPCs were identified, isolated, and grafted onto polymeric discs using a blood compatible star-PEG coating. A porcine in vitro model that demonstrates the specific adhesion of EPCs and their differentiation into vital endothelial-like cells within 10 days in cell culture is presented. We suggest that the rapid adhesion of EPCs to aptamer-coated implants could be useful to promote endothelial wound healing and to prevent increased neointimal hyperplasia. We hypothesize that future in vivo self-endothelialization of blood contacting implants by homing factor mimetic capture molecules for EPCs may bring revolutionary new perspectives towards clinical applications of stem cell and tissue engineering strategies.
The catheter-based Impella 5.0 left ventricular assist device (LVAD) is a powerful and less invasive alternative for patients in cardiogenic shock. The use of this device as a primary mechanical circulatory support strategy in INTERMACS II patients should be evaluated. From April 2014 to August 2014, eight Impella 5.0 devices were implanted in seven patients via the axillary artery access (six right and two left). We analyzed the outcome of the four patients in whom the Impella 5.0 device was implanted for the purpose of primary stabilization of cardiogenic shock (INTERMACS II). The remaining three patients had a contraindication for a permanent LVAD and received the device for prolonged weaning from extracorporeal life support (ECLS) system. The implantation of the Impella 5.0 was technically successful in all patients and resulted in the stabilization of the clinical situation. All four patients could be bridged to a long-term device (n = 3) or to cardiac recovery (n = 1). In one patient, 2 days of ECLS support was necessary because of pump thrombosis after 31 days of Impella 5.0 support. One patient with bronchopneumonia had the Impella 5.0 exchanged from the right to the left axillary artery after 22 days of support because of the progressive loss of purge flow and the need for longer bridging to a permanent LVAD. The last patient was supported for giant-cell myocarditis for 22 days and bridged to cardiac recovery. All patients were transferred to the intensive care unit with the Impella device in place. In INTERMACS II situations, the implantation of the Impella 5.0 via the right or left axillary access allowed additional time for decision making. Early patient mobilization, including walking with the Impella device in place, optimized the conditions for either weaning or the implantation of a permanent LVAD. This novel technique of left axillary approach leads to more flexibility in the case of anatomical- or device-related contraindications to right-side access, or when the device needs to be exchanged while continuous support is necessary.
BackgroundThe objective of this study was to evaluate the outcome of left ventricular assist device (LVAD) implantation after initial extracorporeal life support (ECLS) in patients with cardiogenic shock and the incidence of post implantation right ventricular failure.Methods & resultsAll patients on ECLS therapy for cardiogenic shock prior to LVAD implantation (n = 15) between October 2011 and January 2014 were analyzed. Baseline patient characteristics, as well as detailed pre-operative treatment and postoperative outcome data were collected retrospectively. At time of admission to our unit all patients were classified INTERMACS II or higher (12 [80%] INTERMACS I). Improvement to INTERMACS III temporary cardiac support (TCS) at time of LVAD implantation was successful in 14 patients (93.3%). End-organ function recovered during ECLS support. No patient needed ongoing ECLS or additional right ventricular support after LVAD implantation. Both in-hospital and 30-day mortality was 6.7% (n = 1). The median duration of LVAD support was 687.9 ± 374.5 days. At the end of the study (follow-up 810.7 +/- 338.9 days), 13 (86.7%) patients were alive. The majority of patients (10 [66.7%]) remained on LVAD support. Transplantation could be performed in 1 (6.7%) patient, 2 (13.3%) patients could be successfully weaned.ConclusionLVAD implantation in ECLS patients leads to improvement of INTERMACS level to INTERMACS III TCS status. Excellent mid-term survival comparable to true INTERMACS III-IV patients could be shown. ECLS prior to LVAD as a bridge-to-bridge therapy may help to lower mortality in primarily unstable patients.
The layer-by-layer technique, which allows simple preparation of polyelectrolyte multilayers, came into the focus of research for development of functionalized medical devices. Numerous literature exist that concentrate on the film build-up and the behaviour of cells on polyelectrolyte multilayers. However, in case of very soft polyelectrolyte multilayers, studies of the cell behaviour on these films are sometimes misleading with regard to clinical applications because cells do not die due to cytotoxicity but due to apoptosis by missing cell adhesion. It turns out that the adhesion in vitro, and thus, the viability of cells on polyelectrolyte multilayers is mostly influenced by their mechanical properties. In order to decide, which polyelectrolyte multilayers are suitable for implants, we take this problem into account by putting the substrates with soft films on top of pre-cultured human primary endothelial cells ('reverse assay'). Hence, the present work aims giving a more complete and reliable study of typical polyelectrolyte multilayers with regard to clinical applications. In particular, coatings consisting of hyaluronic acid and chitosan as natural polymers and sulfonated polystyrene and polyallylamine hydrochlorite as synthetic polymers were studied. The adsorption of polyelectrolytes was characterized by physico-chemical methods which show regular buildup. Biological examination of the native or modified polyelectrolyte multilayers was based on their effect to cell adhesion and morphology of endothelial cells by viability assays, immunostaining and scanning electron microscopy. Using the standard method, which is typically applied in literature--seeding cells on top of films--shows that the best adhesion and thus, viability can be achieved using sulfonated polystyrene/polyallylamine hydrochlorite. However, putting the films on top of endothelial cells reveals that hyaluronic acid/chitosan may also be suitable for clinical applications: This result is especially remarkable, since hyaluronic acid and chitosan mediate per se no cytotoxic effects, whereas the individual polyelectrolytes, sulfonated polystyrene and polyallylamine hydrochlorite, and their complexes show slight cytotoxicity.
This study demonstrates mechanical approximation of both mitral valve annulus edges with improved mitral valve annular coaptation by PMVR using the MitraClip® system, which correlates with residual MR in patients with MR.
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