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.

Use of the AB5000 ventricular assist device in cardiogenic shock after acute myocardial infarction.

BACKGROUND: The mortality rate of patients experiencing acute myocardial infarction (AMI) complicated by cardiogenic shock remains high. After conventional therapies have failed, ventricular assist devices (VADs) have been used to bridge patients to recovery or transplantation. METHODS: A voluntary US registry was established to track all patients implanted with the AB5000 VAD. We report the results of the first 100 patients in the registry with the indication of AMI cardiogenic shock. Data were retrospectively reviewed for demographics, preimplant condition, surgical techniques, and outcomes. Survival was assessed at 30 days after VAD explant or at discharge. Myocardial recovery (subset of survival) was defined as satisfactory unassisted native cardiac function for 30 days after VAD explant or at discharge. RESULTS: Forty patients (40%) survived to 30 days after VAD explant or discharge of the first 100 patients. Of the survivors, 63% (n = 25) experienced myocardial recovery. Patients who recovered required an average of 25 +/- 22 days of VAD support. The estimated survival after explant for the recovery patients at 2 years after VAD explant was 78%. CONCLUSIONS: Results from this nationwide registry suggest that VADs can restore normal hemodynamics and support recovery of native cardiac function in the majority of survivors when conventional therapies fail. However, a longer duration of support than previously recognized may be required. In the absence of clinical guidelines, early aggressive use of VAD support in AMI complicated by cardiogenic shock may improve outcomes, and recovery of native cardiac function should always be the primary goal.

Interwoven four-compartment capillary membrane technology for three-dimensional perfusion with decentralized mass exchange to scale up embryonic stem cell culture.

We describe hollow fiber-based three-dimensional (3D) dynamic perfusion bioreactor technology for embryonic stem cells (ESC) which is scalable for laboratory and potentially clinical translation applications. We added 2 more compartments to the typical 2-compartment devices, namely an additional media capillary compartment for countercurrent 'arteriovenous' flow and an oxygenation capillary compartment. Each capillary membrane compartment can be perfused independently. Interweaving the 3 capillary systems to form repetitive units allows bioreactor scalability by multiplying the capillary units and provides decentralized media perfusion while enhancing mass exchange and reducing gradient distances from decimeters to more physiologic lengths of <1 mm. The exterior of the resulting membrane network, the cell compartment, is used as a physically active scaffold for cell aggregation; adjusting intercapillary distances enables control of the size of cell aggregates. To demonstrate the technology, mouse ESC (mESC) were cultured in 8- or 800-ml cell compartment bioreactors. We were able to confirm the hypothesis that this bioreactor enables mESC expansion qualitatively comparable to that obtained with Petri dishes, but on a larger scale. To test this, we compared the growth of 129/SVEV mESC in static two-dimensional Petri dishes with that in 3D perfusion bioreactors. We then tested the feasibility of scaling up the culture. In an 800-ml prototype, we cultured approximately 5 x 10(9) cells, replacing up to 800 conventional 100-mm Petri dishes. Teratoma formation studies in mice confirmed protein expression and gene expression results with regard to maintaining 'stemness' markers during cell expansion.

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.