Use of the Impella 2.5 for prophylactic circulatory support during elective high-risk percutaneous coronary intervention.

BACKGROUND: Patients undergoing percutaneous coronary intervention (PCI) who are at high risk for cardiovascular collapse during the procedure may benefit from prophylactic circulatory support. The objective was to evaluate the safety and feasibility of prophylactic use of the Impella 2.5 during high-risk PCI. METHODS AND MATERIALS: We used the Impella 2.5 for partial circulatory support during 60 consecutive elective high-risk PCI cases over 20 months. All patients either were deemed inoperable by the cardiac surgeons or were offered bypass surgery but declined. RESULTS: The patients had multiple risk factors including hypertension (95%), diabetes (52%), chronic pulmonary disease (23%), prior myocardial infarction (62%) and prior bypass surgery (18%). Forty-five percent presented with acute coronary syndrome. The mean left ventricular ejection fraction was 23%±15%. Nearly all patients had multivessel disease (93%), and 60% had left main disease. The average SYNTAX score was 30±9. Despite lesion complexity and high-risk factors, we achieved an angiographic success rate of 96%. Left main lesions were treated in 55% of the patients, and 83% of patients had multiple lesions treated. There was one procedural death. At 30 days postintervention, mortality was 5%, and rates of myocardial infarction, stroke, target vessel revascularization and urgent bypass surgery were 0%. CONCLUSIONS: The single-center experience reported here demonstrates that use of the Impella 2.5 during high-risk PCI in the "real world" - outside the controlled environment of a clinical trial - is safe and feasible.

Evaluation of primary human liver cells in bioreactor cultures for extracorporeal liver support on the basis of urea production.

Primary human liver cells from donor organs unsuitable for transplantation were cultivated in bioreactors developed for extracorporeal liver support. Because each system contains cells originating from an individual organ, each bioreactor culture must be individually characterized. The objective of this study was to identify suitable decisive parameters for the evaluation of cell culture performance. We analyzed the data from 47 bioreactor cultures containing 437 +/- 110 g of cells. Choosing urea production as the decisive parameter, the bioreactor cultures were divided into high-performance (daily urea production > or = 110 mg per bioreactor between culture days 3 and 14) and low-performance cultures. Comparing the mean courses of the groups revealed a significant distinction in most other investigated biochemical parameters. In conclusion, urea production seems to be an appropriate parameter for evaluating the performance of liver cell cultures in bioreactors because it corresponds to all other evaluated parameters of cell function.

Mouse fetal liver cells in artificial capillary beds in three-dimensional four-compartment bioreactors.

Bioreactors containing porcine or adult human hepatocytes have been used to sustain acute liver failure patients until liver transplantation. However, prolonged function of adult hepatocytes has not been achieved due to compromised proliferation and viability of adult cells in vitro. We investigated the use of fetal hepatocytes as an alternative cell source in bioreactors. Mouse fetal liver cells from gestational day 17 possessed intermediate differentiation and function based on their molecular profile. When cultured in a three-dimensional four-compartment hollow fiber-based bioreactor for 3 to 5 weeks these cells formed neo-tissues that were characterized comprehensively. Albumin liberation, testosterone metabolism, and P450 induction were demonstrated. Histology showed predominant ribbon-like three-dimensional structures composed of hepatocytes between hollow fibers. High positivity for proliferating cell nuclear antigen and Ki-67 and low positivity for terminal dUTP nick-end labeling indicated robust cell proliferation and survival. Most cells within these ribbon arrangements were albumin-positive. In addition, cells in peripheral zones were simultaneously positive for alpha-fetoprotein, cytokeratin-19, and c-kit, indicating their progenitor phenotype. Mesenchymal components including endothelial, stellate, and smooth muscle cells were also observed. Thus, fetal liver cells can survive, proliferate, differentiate, and function in a three-dimensional perfusion culture system while maintaining a progenitor pool, reflecting an important advance in hepatic tissue engineering.

Mathematical and experimental analyses of antibody transport in hollow-fiber-based specific antibody filters.

We are developing hollow fiber-based specific antibody filters (SAFs) that selectively remove antibodies of a given specificity directly from whole blood, without separation of the plasma and cellular blood components and with minimal removal of plasma proteins other than the targeted pathogenic antibodies. A principal goal of our research is to identify the primary mechanisms that control antibody transport within the SAF and to use this information to guide the choice of design and operational parameters that maximize the SAF-based antibody removal rate. In this study, we formulated a simple mathematical model of SAF-based antibody removal and performed in vitro antibody removal experiments to test key predictions of the model. Our model revealed three antibody transport regimes, defined by the magnitude of the Damköhler number Da (characteristic antibody-binding rate/characteristic antibody diffusion rate): reaction-limited (Da /= 10). For a given SAF geometry, blood flow rate, and antibody diffusivity, the highest antibody removal rate was predicted for diffusion-limited antibody transport. Additionally, for diffusion-limited antibody transport the predicted antibody removal rate was independent of the antibody-binding rate and hence was the same for any antibody-antigen system and for any patient within one antibody-antigen system. Using SAF prototypes containing immobilized bovine serum albumin (BSA), we measured anti-BSA removal rates consistent with transport in the intermediate regime (Da approximately 3). We concluded that initial SAF development work should focus on achieving diffusion-limited antibody transport by maximizing the SAF antibody-binding capacity (hence maximizing the characteristic antibody-binding rate). If diffusion-limited antibody transport is achieved, the antibody removal rate may be raised further by increasing the number and length of the SAF fibers and by increasing the blood flow rate through the SAF.