Cavopulmonary assist for the failing Fontan circulation: impact of ventricular function on mechanical support strategy

Mechanical circulatory support--either ventricular assist device (VAD, left-sided systemic support) or cavopulmonary assist device (CPAD, right-sided support)--has been suggested as treatment for Fontan failure. The selection of left- versus right-sided support for failing Fontan has not been previously defined. Computer simulation and mock circulation models of pediatric Fontan patients (15-25 kg) with diastolic, systolic, and combined systolic and diastolic dysfunction were developed. The global circulatory response to assisted Fontan flow using VAD (HeartWare HVAD, Miami Lakes, FL) support, CPAD (Viscous Impeller Pump, Indianapolis, IN) support, and combined VAD and CPAD support was evaluated. Cavopulmonary assist improves failing Fontan circulation during diastolic dysfunction but preserved systolic function. In the presence of systolic dysfunction and elevated ventricular end-diastolic pressure (VEDP), VAD support augments cardiac output and diminishes VEDP, while increased preload with cavopulmonary assist may worsen circulatory status. Fontan circulation can be stabilized to biventricular values with modest cavopulmonary assist during diastolic dysfunction. Systemic VAD support may be preferable to maintain systemic output during systolic dysfunction. Both systemic and cavopulmonary support may provide best outcome during combined systolic and diastolic dysfunction. These findings may be useful to guide clinical cavopulmonary assist strategies in failing Fontan circulations

Bovine Model of Doxorubicin-Induced Cardiomyopathy

Left ventricular assist devices (LVADs) constitute a recent advance in heart failure (HF) therapeutics. As the rigorous experimental assessment of LVADs in HF requires large animal models, our objective was to develop a bovine model of cardiomyopathy. Male calves (n = 8) were used. Four animals received 1.2 mg/kg intravenous doxorubicin weekly for seven weeks and four separate animals were studied as controls. Doxorubicin-treated animals were followed with weekly echocardiography. Target LV dysfunction was defined as an ejection fraction ≤35%. Sixty days after initiating doxorubicin, a terminal study was performed to determine hemodynamic, histological, biochemical, and molecular parameters. All four doxorubicin-treated animals exhibited significant (P < 0.05) contractile dysfunction, with target LV dysfunction achieved in three animals. Doxorubicin-treated hearts exhibited significantly reduced coronary blood flow and interstitial fibrosis and significantly increased apoptosis and myocyte size. Gene expression of atrial natriuretic factor increased more than 3-fold. Plasma norepinephrine and epinephrine levels were significantly increased early and late during the development of cardiomyopathy, respectively. We conclude that sequential administration of intravenous doxorubicin in calves induces a cardiomyopathy with many phenotypic hallmarks of the failing human heart. This clinically-relevant model may be useful for testing pathophysiologic responses to LVADs in the context of HF

Transapical miniaturized ventricular assist device: Design and initial testing

BackgroundLeft ventricular assist devices are increasingly used to treat patients with advanced and otherwise refractory heart failure as bridge to transplant or destination therapy. We evaluated a new miniaturized left ventricular assist device that requires minimal surgery for implantation, potentially allowing implantation in earlier stage heart failure.MethodsHeartWare (Miami Lakes, Fla) developed transapical miniaturized ventricular assist device. Acute (n = 4), 1-week (n = 2), and 30-day (n = 4) bovine model experiments evaluated hemodynamic efficacy and biocompatibility of the device, which was implanted through small left thoracotomy with single insertion at apex of left ventricle without cardiopulmonary bypass. The device outflow cannula was positioned across the aortic valve. The international normalized ratio was maintained between 2.0 and 2.5 with warfarin. Hemodynamic, echocardiographic, fluoroscopic, hematologic, and blood chemistry measurements were evaluated.ResultsThe device was successfully implanted through the left ventricular apex in all 10 animals. The device was operated at 15,000 ± 1000 rpm (power consumption, 3.5–6.0 W). The device maintained normal end-organ perfusion with no significant hemolysis (0–30 mg/dL). There were no pump failures or device-related complications. At autopsy, no abnormalities were seen in endocardium, aortic valve leaflets, or aortic root. There was no evidence of thromboembolism or abnormalities in any peripheral end organs.ConclusionsWe successfully demonstrated feasibility of a novel intraventricular assist device that can be completely implanted through left ventricular apex. This transapical surgical approach eliminates needs for sternotomy, device pocket, cardiopulmonary bypass, ventricular coring, and construction of an outflow graft anastomosis

The Conservation Reserve Program: Economic Implications for Rural America

This report estimates the impact that high levels of enrollment in the Conservation Reserve Program (CRP) have had on economic trends in rural counties since the program's inception in 1985 until today. The results of a growth model and quasi-experimental control group analysis indicate no discernible impact by the CRP on aggregate county population trends. Aggregate employment growth may have slowed in some high-CRP counties, but only temporarily. High levels of CRP enrollment appear to have affected farm-related businesses over the long run, but growth in the number of other nonfarm businesses moderated CRP's impact on total employment. If CRP contracts had ended in 2001, simulation models suggest that roughly 51 percent of CRP land would have returned to crop production, and that spending on outdoor recreation would decrease by as much as $300 million per year in rural areas. The resulting impacts on employment and income vary widely among regions having similar CRP enrollments, depending upon local economic conditions.Community/Rural/Urban Development, Land Economics/Use,

Economic evaluation of access to musculoskeletal care: The case of waiting for total knee arthroplasty

BACKGROUND: The projected demand for total knee arthroplasty is staggering. At its root, the solution involves increasing supply or decreasing demand. Other developed nations have used rationing and wait times to distribute this service. However, economic impact and cost-effectiveness of waiting for TKA is unknown. METHODS: A Markov decision model was constructed for a cost-utility analysis of three treatment strategies for end-stage knee osteoarthritis: 1) TKA without delay, 2) a waiting period with no non-operative treatment and 3) a non-operative treatment bridge during that waiting period in a cohort of 60 year-old patients. Outcome probabilities and effectiveness were derived from the literature. Costs were estimated from the societal perspective with national average Medicare reimbursement. Effectiveness was expressed in quality-adjusted life years (QALYs) gained. Principal outcome measures were average incremental costs, effectiveness, and quality-adjusted life years; and net health benefits. RESULTS: In the base case, a 2-year wait-time both with and without a non-operative treatment bridge resulted in a lower number of average QALYs gained (11.57 (no bridge) and 11.95 (bridge) vs. 12.14 (no delay). The average cost was $1,660 higher for TKA without delay than wait-time with no bridge, but$1,810 less than wait-time with non-operative bridge. The incremental cost-effectiveness ratio comparing wait-time with no bridge to TKA without delay was $2,901/QALY. When comparing TKA without delay to waiting with non-operative bridge, TKA without delay produced greater utility at a lower cost to society. CONCLUSIONS: TKA without delay is the preferred cost-effective treatment strategy when compared to a waiting for TKA without non-operative bridge. TKA without delay is cost saving when a non-operative bridge is used during the waiting period. As it is unlikely that patients waiting for TKA would not receive non-operative treatment, TKA without delay may be an overall cost-saving health care delivery strategy. Policies aimed at increasing the supply of TKA should be considered as savings exist that could indirectly fund those strategies

Molecular Valves for Controlling Gas Phase Transport Made from Discrete Angstrom-Sized Pores in Graphene

An ability to precisely regulate the quantity and location of molecular flux is of value in applications such as nanoscale 3D printing, catalysis, and sensor design. Barrier materials containing pores with molecular dimensions have previously been used to manipulate molecular compositions in the gas phase, but have so far been unable to offer controlled gas transport through individual pores. Here, we show that gas flux through discrete angstrom-sized pores in monolayer graphene can be detected and then controlled using nanometer-sized gold clusters, which are formed on the surface of the graphene and can migrate and partially block a pore. In samples without gold clusters, we observe stochastic switching of the magnitude of the gas permeance, which we attribute to molecular rearrangements of the pore. Our molecular valves could be used, for example, to develop unique approaches to molecular synthesis that are based on the controllable switching of a molecular gas flux, reminiscent of ion channels in biological cell membranes and solid state nanopores.Comment: to appear in Nature Nanotechnolog

Ultrathin Oxide Films by Atomic Layer Deposition on Graphene

In this paper, a method is presented to create and characterize mechanically robust, free standing, ultrathin, oxide films with controlled, nanometer-scale thickness using Atomic Layer Deposition (ALD) on graphene. Aluminum oxide films were deposited onto suspended graphene membranes using ALD. Subsequent etching of the graphene left pure aluminum oxide films only a few atoms in thickness. A pressurized blister test was used to determine that these ultrathin films have a Young's modulus of 154 \pm 13 GPa. This Young's modulus is comparable to much thicker alumina ALD films. This behavior indicates that these ultrathin two-dimensional films have excellent mechanical integrity. The films are also impermeable to standard gases suggesting they are pinhole-free. These continuous ultrathin films are expected to enable new applications in fields such as thin film coatings, membranes and flexible electronics.Comment: Nano Letters (just accepted

Ultra-strong Adhesion of Graphene Membranes

As mechanical structures enter the nanoscale regime, the influence of van der Waals forces increases. Graphene is attractive for nanomechanical systems because its Young's modulus and strength are both intrinsically high, but the mechanical behavior of graphene is also strongly influenced by the van der Waals force. For example, this force clamps graphene samples to substrates, and also holds together the individual graphene sheets in multilayer samples. Here we use a pressurized blister test to directly measure the adhesion energy of graphene sheets with a silicon oxide substrate. We find an adhesion energy of 0.45 \pm 0.02 J/m2 for monolayer graphene and 0.31 \pm 0.03 J/m2 for samples containing 2-5 graphene sheets. These values are larger than the adhesion energies measured in typical micromechanical structures and are comparable to solid/liquid adhesion energies. We attribute this to the extreme flexibility of graphene, which allows it to conform to the topography of even the smoothest substrates, thus making its interaction with the substrate more liquid-like than solid-like.Comment: to appear in Nature Nanotechnolog

Selective Molecular Sieving through Porous Graphene

Membranes act as selective barriers and play an important role in processes such as cellular compartmentalization and industrial-scale chemical and gas purification. The ideal membrane should be as thin as possible to maximize flux, mechanically robust to prevent fracture, and have well-defined pore sizes to increase selectivity. Graphene is an excellent starting point for developing size selective membranes because of its atomic thickness, high mechanical strength, relative inertness, and impermeability to all standard gases. However, pores that can exclude larger molecules, but allow smaller molecules to pass through have to be introduced into the material. Here we show UV-induced oxidative etching can create pores in micrometre-sized graphene membranes and the resulting membranes used as molecular sieves. A pressurized blister test and mechanical resonance is used to measure the transport of a variety of gases (H2, CO2, Ar, N2, CH4, and SF6) through the pores. The experimentally measured leak rates, separation factors, and Raman spectrum agree well with models based on effusion through a small number of angstrom-sized pores.Comment: to appear in Nature Nanotechnolog

Inland Pacific Northwest pasture calendar

The Inland Pacific Northwest (PNW) region, historically referred to as the 'Inland Empire', extends from the Cascade Mountains in the west to former Glacial Lake Missoula in the Rockies in the east and from the Canadian border in the north past the Snake River Canyon in the south. The greatest agricultural enterprises are hay (from various forage species), irrigated and non-irrigated grassland pastures, rangelands, and livestock production. It is also home to numerous wildlife species and flyways for migrating birds. The Inland PNW Pasture Calendar is designed to be a comprehensive guide for improved grassland management in support of forage-livestock systems. Applying the principles described will lead to improved regional economic, ecological, and social sustainability. This publication describes the opportunities and challenges of sustainably raising harvested and grazed forages and developing forage-livestock systems in this incredibly diverse environment. Appendix Chapters provide key information on grass / legume / forb species, how pasture species grow and regrow, soil nutrient management and organic matter, grazing philosophies and systems, matching grazing needs for pasture production, and forage-related animal health issues. Learning these key principles and following best management practices described will lead to improved sustainability of forage-livestock systems