Fluorescent biological aerosol particles: Concentrations, emissions, and exposures in a northern California residence.

Residences represent an important site for bioaerosol exposure. We studied bioaerosol concentrations, emissions, and exposures in a single-family residence in northern California with 2 occupants using real-time instrumentation during 2 monitoring campaigns (8 weeks during August-October 2016 and 5 weeks during January-March 2017). Time- and size-resolved fluorescent biological aerosol particles (FBAP) and total airborne particles were measured in real time in the kitchen using an ultraviolet aerodynamic particle sizer (UVAPS). Time-resolved occupancy status, household activity data, air-change rates, and spatial distribution of size-resolved particles were also determined throughout the house. Occupant activities strongly influenced indoor FBAP levels. Indoor FBAP concentrations were an order of magnitude higher when the house was occupied than when the house was vacant. Applying an integral material-balance approach, geometric mean of total FBAP emissions from human activities observed to perturb indoor levels were in the range of 10-50 million particles per event. During the summer and winter campaigns, occupants spent an average of 10 and 8.5 hours per day, respectively, awake and at home. During these hours, the geometric mean daily-averaged FBAP exposure concentration (1-10 µm diameter) was similar for each subject at 40 particles/L for summer and 29 particles/L for winter.

Detailed investigation of ventilation rates and airflow patterns in a northern California residence.

Building ventilation rates and indoor airflow conditions influence occupants' exposure to indoor air pollutants. By making time- and space-resolved measurement of 3 inert tracers steadily released in a single-family house in California for 8 weeks in summer and 5 weeks in winter, this study quantifies the air change rate of the living zone with 2-hour time resolution; estimates airflow rates between the living zone, attic, and crawlspace; and characterizes mixing of air in the split-level living space. Occupant behaviors altered the air change rates, primarily through opening windows and secondarily through operating the heating system. The air change rate correlated with the number of window openings, accounting for 57% of the variability measured across 2 seasons. There were substantial upward interzonal airflows between the crawlspace, living zone, and attic; downward airflows were negligible by comparison. More than 70% of the airflow entering the living zone in the winter and at night during summer came through the crawlspace, rather than directly from outdoors. The airflow from the living zone to the attic increased with the attic-outdoor temperature difference, indicating that buoyancy associated with solar heating of the attic induced airflow from the living zone, increasing the air change rate.

Comparative genomics of Mortierella elongata and its bacterial endosymbiont Mycoavidus cysteinexigens.

Endosymbiosis of bacteria by eukaryotes is a defining feature of cellular evolution. In addition to well-known bacterial origins for mitochondria and chloroplasts, multiple origins of bacterial endosymbiosis are known within the cells of diverse animals, plants and fungi. Early-diverging lineages of terrestrial fungi harbor endosymbiotic bacteria belonging to the Burkholderiaceae. We sequenced the metagenome of the soil-inhabiting fungus Mortierella elongata and assembled the complete circular chromosome of its endosymbiont, Mycoavidus cysteinexigens, which we place within a lineage of endofungal symbionts that are sister clade to Burkholderia. The genome of M. elongata strain AG77 features a core set of primary metabolic pathways for degradation of simple carbohydrates and lipid biosynthesis, while the M. cysteinexigens (AG77) genome is reduced in size and function. Experiments using antibiotics to cure the endobacterium from the host demonstrate that the fungal host metabolism is highly modulated by presence/absence of M. cysteinexigens. Independent comparative phylogenomic analyses of fungal and bacterial genomes are consistent with an ancient origin for M. elongata - M. cysteinexigens symbiosis, most likely over 350 million years ago and concomitant with the terrestrialization of Earth and diversification of land fungi and plants.

Using advanced mass spectrometry techniques to fully characterize atmospheric organic carbon: current capabilities and remaining gaps.

Organic compounds in the atmosphere vary widely in their molecular composition and chemical properties, so no single instrument can reasonably measure the entire range of ambient compounds. Over the past decade, a new generation of in situ, field-deployable mass spectrometers has dramatically improved our ability to detect, identify, and quantify these organic compounds, but no systematic approach has been developed to assess the extent to which currently available tools capture the entire space of chemical identity and properties that is expected in the atmosphere. Reduced-parameter frameworks that have been developed to describe atmospheric mixtures are exploited here to characterize the range of chemical properties accessed by a suite of instruments. Multiple chemical spaces (e.g. oxidation state of carbon vs. volatility, and oxygen number vs. carbon number) were populated with ions measured by several mass spectrometers, with gas- and particle-phase α-pinene oxidation products serving as the test mixture of organic compounds. Few gaps are observed in the coverage of the parameter spaces by the instruments employed in this work, though the full extent to which comprehensive measurement was achieved is difficult to assess due to uncertainty in the composition of the mixture. Overlaps between individual ions and regions in parameter space were identified, both between gas- and particle-phase measurements, and within each phase. These overlaps were conservatively found to account for little (<10%) of the measured mass. However, challenges in identifying overlaps and in accurately converting molecular formulas into chemical properties (such as volatility or reactivity) highlight a continued need to incorporate structural information into atmospheric measurements.

Ozone production chemistry in the presence of urban plumes.

Ozone pollution affects human health, especially in urban areas on hot sunny days. Its basic photochemistry has been known for decades and yet it is still not possible to correctly predict the high ozone levels that are the greatest threat. The CalNex_SJV study in Bakersfield CA in May/June 2010 provided an opportunity to examine ozone photochemistry in an urban area surrounded by agriculture. The measurement suite included hydroxyl (OH), hydroperoxyl (HO2), and OH reactivity, which are compared with the output of a photochemical box model. While the agreement is generally within combined uncertainties, measured HO2 far exceeds modeled HO2 in NOx-rich plumes. OH production and loss do not balance as they should in the morning, and the ozone production calculated with measured HO2 is a decade greater than that calculated with modeled HO2 when NO levels are high. Calculated ozone production using measured HO2 is twice that using modeled HO2, but this difference in calculated ozone production has minimal impact on the assessment of NOx-sensitivity or VOC-sensitivity for midday ozone production. Evidence from this study indicates that this important discrepancy is not due to the HO2 measurement or to the sampling of transported plumes but instead to either emissions of unknown organic species that accompany the NO emissions or unknown photochemistry involving nitrogen oxides and hydrogen oxides, possibly the hypothesized reaction OH + NO + O2 → HO2 + NO2.

Indoor chemistry: research opportunities and challenges.

In this editorial, we have highlighted key research opportunities and challenges in four topical themes for indoor chemistry: human occupants as agents influencing indoor chemistry; oxidative chemistry; surface phenomena; and semivolatile organic compounds. In each case, enough prior work has been done to demonstrate the importance of the theme and to create a foundation for future studies. Extensive achievements and ongoing progress in (outdoor) atmospheric chemistry­both in the analytical methods developed and in the scientific knowledge created­also contribute to a strong foundation from which to achieve rapid research progress in this exciting new domain.

Overview of HOMEChem: House Observations of Microbial and Environmental Chemistry.

The House Observations of Microbial and Environmental Chemistry (HOMEChem) study is a collaborative field investigation designed to probe how everyday activities influence the emissions, chemical transformations and removal of trace gases and particles in indoor air. Sequential and layered experiments in a research house included cooking, cleaning, variable occupancy, and window-opening. This paper describes the overall design of HOMEChem and presents preliminary case studies investigating the concentrations of reactive trace gases, aerosol particles, and surface films. Cooking was a large source of VOCs, CO2, NOx, and particles. By number, cooking particles were predominantly in the ultrafine mode. Organic aerosol dominated the submicron mass, and, while variable between meals and throughout the cooking process, was dominated by components of hydrocarbon character and low oxygen content, similar to cooking oil. Air exchange in the house ensured that cooking particles were present for only short periods. During unoccupied background intervals, particle concentrations were lower indoors than outdoors. The cooling coils of the house ventilation system induced cyclic changes in water soluble gases. Even during unoccupied periods, concentrations of many organic trace gases were higher indoors than outdoors, consistent with housing materials being potential sources of these compounds to the outdoor environment. Organic material accumulated on indoor surfaces, and exhibited chemical signatures similar to indoor organic aerosol.

Organic nitrate chemistry and its implications for nitrogen budgets in an isoprene- and monoterpene-rich atmosphere: constraints from aircraft (SEAC4RS) and ground-based (SOAS) observations in the Southeast US.

Formation of organic nitrates (RONO2) during oxidation of biogenic volatile organic compounds (BVOCs: isoprene, monoterpenes) is a significant loss pathway for atmospheric nitrogen oxide radicals (NOx), but the chemistry of RONO2 formation and degradation remains uncertain. Here we implement a new BVOC oxidation mechanism (including updated isoprene chemistry, new monoterpene chemistry, and particle uptake of RONO2) in the GEOS-Chem global chemical transport model with ∼25 × 25 km2 resolution over North America. We evaluate the model using aircraft (SEAC4RS) and ground-based (SOAS) observations of NOx, BVOCs, and RONO2 from the Southeast US in summer 2013. The updated simulation successfully reproduces the concentrations of individual gas- and particle-phase RONO2 species measured during the campaigns. Gas-phase isoprene nitrates account for 25-50% of observed RONO2 in surface air, and we find that another 10% is contributed by gas-phase monoterpene nitrates. Observations in the free troposphere show an important contribution from long-lived nitrates derived from anthropogenic VOCs. During both campaigns, at least 10% of observed boundary layer RONO2 were in the particle phase. We find that aerosol uptake followed by hydrolysis to HNO3 accounts for 60% of simulated gas-phase RONO2 loss in the boundary layer. Other losses are 20% by photolysis to recycle NOx and 15% by dry deposition. RONO2 production accounts for 20% of the net regional NOx sink in the Southeast US in summer, limited by the spatial segregation between BVOC and NOx emissions. This segregation implies that RONO2 production will remain a minor sink for NOx in the Southeast US in the future even as NOx emissions continue to decline.

An ecosystem-scale perspective of the net land methanol flux: synthesis of micrometeorological flux measurements.

Methanol is the second most abundant volatile organic compound in the troposphere and plays a significant role in atmospheric chemistry. While there is consensus about the dominant role of living plants as the major source and the reaction with OH as the major sink of methanol, global methanol budgets diverge considerably in terms of source/sink estimates reflecting uncertainties in the approaches used to model, and the empirical data used to separately constrain these terms. Here we compiled micrometeorological methanol flux data from eight different study sites and reviewed the corresponding literature in order to provide a first cross-site synthesis of the terrestrial ecosystem-scale methanol exchange and present an independent data-driven view of the land-atmosphere methanol exchange. Our study shows that the controls of plant growth on the production, and thus the methanol emission magnitude, and stomatal conductance on the hourly methanol emission variability, established at the leaf level, hold across sites at the ecosystem-level. Unequivocal evidence for bi-directional methanol exchange at the ecosystem scale is presented. Deposition, which at some sites even exceeds methanol emissions, represents an emerging feature of ecosystem-scale measurements and is likely related to environmental factors favouring the formation of surface wetness. Methanol may adsorb to or dissolve in this surface water and eventually be chemically or biologically removed from it. Management activities in agriculture and forestry are shown to increase local methanol emission by orders of magnitude; they are however neglected at present in global budgets. While contemporary net land methanol budgets are overall consistent with the grand mean of the micrometeorological methanol flux measurements, we caution that the present approach of simulating methanol emission and deposition separately is prone to opposing systematic errors and does not allow taking full advantage of the rich information content of micrometeorological flux measurements.

Atmospheric benzenoid emissions from plants rival those from fossil fuels.

Despite the known biochemical production of a range of aromatic compounds by plants and the presence of benzenoids in floral scents, the emissions of only a few benzenoid compounds have been reported from the biosphere to the atmosphere. Here, using evidence from measurements at aircraft, ecosystem, tree, branch and leaf scales, with complementary isotopic labeling experiments, we show that vegetation (leaves, flowers, and phytoplankton) emits a wide variety of benzenoid compounds to the atmosphere at substantial rates. Controlled environment experiments show that plants are able to alter their metabolism to produce and release many benzenoids under stress conditions. The functions of these compounds remain unclear but may be related to chemical communication and protection against stress. We estimate the total global secondary organic aerosol potential from biogenic benzenoids to be similar to that from anthropogenic benzenoids (~10 Tg y(-1)), pointing to the importance of these natural emissions in atmospheric physics and chemistry.

Effects of crystalloid, blood, and University of Wisconsin perfusates on weight, water content, and left ventricular compliance in an edema-prone, isolated porcine heart model.

Coronary perfusion with blood and cardioplegic solutions was examined in isolated, arrested, hypothermic porcine hearts. Myocardial water content, heart weight, and left ventricular diastolic pressure-volume curves were measured before and after coronary perfusion. Statistics were based on exponential curve fitting to pressure-volume data and analysis of variance. Thirty-two pig hearts were divided into five experimental groups and a control group; after control measurements, each experimental group underwent three successive coronary perfusions with 1 L of unmodified blood or a solution of controlled osmolarity, 150 mOsm/L (diluted Plegisol solution), 280 mOsm/L (Plegisol solution and albumin), 334 mOsm/L (University of Wisconsin solution), or 380 mOsm/L (Stanford solution). After each perfusion, measurements were repeated. All experiments were completed within 90 minutes. The first perfusion was delayed 20 minutes after excision of the heart to allow for instrumentation. Each experimental group demonstrated a statistically significant increase in heart weight and myocardial water content and a significant decrease in left ventricular compliance after perfusion. Changes were less pronounced with blood than crystalloids. Edema effects were minimized but not prevented by hyperosmolarity. University of Wisconsin solution appeared unique in minimizing progressive edema after the first perfusion. Over the 81 perfusions studied, changes in left ventricular compliance were linearly related to heart weight and water content. We conclude that in this model, in which edema sensitivity is increased by delayed perfusion and venous occlusion, edema is minimized but not eliminated by whole blood and University of Wisconsin solution. The model appears useful in assessing properties of cardioplegia vehicles intended for use in the injured myocardium.

Cloning of a Serratia marcescens DNA fragment that induces quinoprotein glucose dehydrogenase-mediated gluconic acid production in Escherichia coli in the presence of stationary phase Serratia marcescens.

Serratia marcescens ER2 was isolated from an endorhizosphere sample based on its high level of mineral phosphate solubilizing (MPS) activity. This phenotype was correlated with expression of the direct oxidation pathway. An ER2 plasmid library constructed in Escherichia coli strain DH5alpha was screened for MPS activity. A recombinant clone DH5alpha (pKG3791) was capable of gluconic acid (GA) production and tricalcium phosphate solubilization but only in the presence of stationary phase ER2 cells. GA production in DH5alpha (pKG3791) was apparently the result of the quinoprotein glucose dehydrogenase activity because AG121 (a Tn5 knockout of gcd) carrying pKG3791 did not produce GA under the same conditions. GA production by DH5alpha (pKG3791) was not observed when ER2 was replaced by another PQQ-producing strain bacterium. These data add to a growing body of evidence that E. coli contains some type of PQQ biosynthesis pathway distinct from those previously characterized in Gram-negative bacteria and that these genes may be induced under appropriate conditions.

Predictable reduction in left ventricular stroke work and oxygen utilization with an implantable centrifugal pump.

Previous investigations with roller pumps and pneumatic pulsatile assist devices have demonstrated that nearly complete capture of normal left ventricular end-diastolic volume was necessary for appreciable reductions in oxygen consumption and stroke work. We tested the hypothesis that a centrifugal pump would decrease left ventricular stroke work and oxygen consumption as a function of pump flow. Ten sheep (35 to 50 kg) were instrumented and placed on left atrium-to-descending aorta bypass with a small, lightweight (112 g), implantable centrifugal pump. The relations between pump flow as a percent of cardiac output (% bypass), left ventricular stroke work, and oxygen consumption were studied. Left ventricular stroke work was calculated from the pressure-volume loops obtained with micromanometer and conductance catheters and was indexed per 100 g of left ventricular wet weight. Oxygen consumption was calculated from left main coronary artery blood flow and the arterial-coronary sinus oxygen content difference, normalized to 100 g of left ventricular wet weight and a heart rate of 100 beats/min. Measurements were made in stepwise increments of pump flow from zero to the maximum obtainable and then reversed in similar decrements. Analyses were made for 27 complete runs. Our data demonstrate that reductions in left ventricular stroke work and oxygen consumption were achieved from zero to maximal bypass. There was an approximate 66% and 50% reduction in left ventricular stroke work and oxygen consumption, respectively, at 60% bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical results with the AB-180 left ventricular assist device.

BACKGROUND: This report reviews the initial clinical experience with the AB-180 ventricular assist device. METHODS: Between Dec 1997 and July 2000, the AB-180 was implanted in 17 patients at five institutions. The mean age was 52 years (range 21 to 68 years) and 14 of 17 were male. The indications for implantation were postcardiotomy shock (12 of 17, 70%), decompensated cardiomyopathy (2 of 17, 12%), viral myocarditis (2 of 17, 12%), and acute myocardial infarction (1 of 17, 6%). RESULTS: The mean duration of support was 8.5 days (range 1 to 28 days). In the group of 17 patients, 8 were weaned from the device and 2 underwent transplantation. Four of the weaned patients (4 of 8, 50%) and 1 of the transplant patients (1 of 2, 50%) survived. The overall weaning and survival rates were 58% (10 of 17) and 29% (5 of 17). There were no major device-related complications and no major device malfunctions. CONCLUSIONS: The AB-180 provides reliable circulatory support for reversible forms of heart failure.

Small, low-cost implantable centrifugal pump for short-term circulatory assistance.

BACKGROUND: In 1991, Allegheny General Hospital and Allegheny-Singer Research Institute purchased a centrifugal pump, then a 2-year-old technology, from Medtronic Bio-Medicus, as part of its research program for novel treatments of acute and chronic heart failure. During a 4-year development program, we then established and met goals of durability, performance, thromboresistance, and low cost. METHODS: In vitro testing involved extensive hydraulic characterizations using Penn State mock loops. Calorimetry was used to determine efficiency. Durability studies used heated (37 degrees C) seawater for 28 to 45 days. In vivo studies used 46 sheep to test performance and engineering changes and to determine myocardial oxygen consumption, thromboresistance, and long-term durability. A left atrium-to-aorta circuit was used in all. RESULTS: Hydraulic testing showed no preload sensitivity but moderate afterload sensitivity at all impeller speeds (2,000 to 6,000 rpm). The heat load was low, and overall efficiency was 13% to 15%. Bench durability studies showed no electrical malfunction of the stator or console without degradation of the biomaterials used. Acute in vitro studies showed a near-linear relationship of myocardial oxygen consumption and left ventricular stroke work, pump flow, and pump speed. At speeds of 2 to 3 L/min (50% bypass), left ventricular stroke work and myocardial oxygen consumption were decreased approximately 50%. Additionally, 5 animals have had implants for 28 to 154 days with no macroemboli or microemboli detected in any animal. Hematologic and biochemical studies became normal 3 to 7 days after implantation. Hemolysis was low at less than 10 mg/dL. Clinical costs of the device are estimated to be 80% less than those of currently available devices. CONCLUSIONS: We conclude that an old technology has been made into new technology by application of sound engineering design principles, microchips, and new biomaterials. Qualifying trails for a Food and Drug Agency investigational device exemption application are in progress.

Response of stomatal conductance to drought in ponderosa pine: implications for carbon and ozone uptake.

To gain insight into the limitations imposed by a typical Mediterranean-climate summer drought on the uptake of carbon and ozone in the ponderosa pine (Pinus ponderosa Dougl. ex Laws.) ecosystem, we compared diurnal trends in leaf physiology of young trees in a watered and a control plot located in the Sierra Nevada Mountains, CA, USA (Blodgett Forest, 38 degrees 53' N, 120 degrees 37' W, 1315 m elevation). Predawn water potential of trees in the watered plot remained above -0.3 MPa throughout the growing season, whereas it dropped in the control plot from -0.24 to -0.52 MPa between late May and mid-August. Photosynthesis and stomatal conductance of trees in the watered plot were relatively insensitive to atmospheric vapor pressure deficit (VPD), whereas gas exchange of trees in the control plot varied with changes in soil water, VPD and temperature. Although the 1998 growing season was abnormally wet, we saw a pronounced drought effect at the control site. Over the 2 months following the onset of watering, carbon and ozone uptake were measured on three days at widely spaced intervals. Carbon uptake per unit leaf area by 1-year-old foliage of trees in the control plot was 39, 35 and 30% less, respectively, than in the watered plot, and estimated ozone deposition per unit leaf area (ozone concentration times stomatal conductance) was 36, 46 and 41% less.

Carbon dioxide and water vapor exchange by young and old ponderosa pine ecosystems during a dry summer.

We investigated key factors controlling mass and energy exchange by a young (6-year-old) ponderosa pine (Pinus ponderosa Laws.) plantation on the west side of the Sierra Nevada Mountains and an old-growth ponderosa pine forest (mix of 45- and 250-year-old trees) on the east side of the Cascade Mountains, from June through September 1997. At both sites, we operated eddy covariance systems above the canopy to measure net ecosystem exchange of carbon dioxide and water vapor, and made concurrent meteorological and ecophysiological measurements. Our objective was to understand and compare the controls on ecosystem processes in these two forests. Precipitation is much higher in the young plantation than in the old-growth forest (1660 versus 550 mm year-1), although both forests experienced decreasing soil water availability and increasing vapor pressure deficits (D) as the summer of 1997 progressed. As a result, drought stress increased at both sites during this period, and changes in D strongly influenced ecosystem conductance and net carbon uptake. Ecosystem conductance for a given D was higher in the young pine plantation than in the old-growth forest, but decreased dramatically following several days of high D in late summer, possibly because of xylem cavitation. Net CO2 exchange generally decreased with conductance at both sites, although values were roughly twice as high at the young site. Simulations with the 3-PG model, which included the effect of tree age on fluxes, suggest that, during the fall through spring period, milder temperatures and ample water availability at the young site provide better conditions for photosynthesis than at the old pine site. Thus, over the long-term, the young site can carry more leaf area, and the climatic conditions between fall and spring offset the more severe limitations imposed by summer drought.

Modified fabrication techniques lead to improved centrifugal blood pump performance.

The authors are developing an implantable centrifugal blood pump for short- and medium-term (1-6 months) left ventricular assist. They hypothesized that the application of result dependent modifications to this pump would lead to overall improved performance in long-term implantation studies. Essential requirements for pump operation, such as durability and resistance to clot formation, have been achieved through specialized fabrication techniques. The antithrombogenic character of the pump has been improved through coating at the cannula-housing interfaces and the baffle seal, and through changing the impeller blade material from polysulfone to pyrolytic carbon. The electronic components of the pump have been sealed for implantable use through specialized processes of dipping and potting, and the surfaces of the internal pump components have been treated to increase durability. The device has demonstrated efficacy in five chronic sheep implantation studies of 14, 10, 28, 35, and 154 day duration. Post mortem findings from the 14 day experiment showed stable fibrin entangled around the impeller shaft and blades. After pump modification, autopsy findings of the 10 day study showed no evidence of clot. Additionally, the results of the 28 day experiment showed only a small (2.0 mm) ring of fibrin at the shaft-seal interface. In the 35 and 154 day experiments, redesign of the stators have resulted in improved motor corrosion resistance. The 35 day study showed a small, 0.5 mm wide fibrin deposit at the lip seal, but no motor failure. In the 154 day experiment, the motor failed because of stator fluid corrosion, while the explanted pump was devoid of thrombus. Based on these findings, the authors believe that these pump refinements have contributed significantly to improvements in durability and resistance to clot formation.

Development of an implantable centrifugal blood pump.

The efficacy of centrifugal pumps for short-term (0-30 days) ventricular support has been widely reported and favorably compared with pulsatile systems. A small, durable, implantable centrifugal blood pump is being developed for medium-term use (up to 6 months). The pump is based on the Medtronic Hemadyne system that has existed in multiple forms over the past 30 years. The pump is approximately the size of a tennis ball, weighs 240 g, and is comprised of a 2.5 cm plastic impeller driven by a radially coupled brushless DC motor. In vitro hydraulic performance was recorded over a wide range of flow conditions on a mock circulatory loop. The pump generated 7 L/min flow against an afterload of 100 mmHg pressure, with a maximum power draw of 10.4 watts. Pulsatile flow was preserved when placed in conjunction with a simulated left ventricle. In vivo testing was performed in 10 healthy sheep for 10-292 hr. Heparin was used to facilitate cannulation, and no anticoagulation was administered after pump implantation. Blood chemistries reflecting hematologic, pulmonary, renal, and hepatic functions were recorded and demonstrated no adverse effects with normal pump operation. Complications were related to kinking of blood conduits and thrombus formation within the cannulae. These results are encouraging and warrant further studies to prove feasibility of this pump as a medium-term implantable ventricular assist device.

End organ function with prolonged nonpulsatile circulatory support.

The hypothesis tested in these studies was that long-term circulatory support with a nonpulsatile device is safe and causes no end organ dysfunction. An inexpensive, small centrifugal pump with a 7 L/min capacity was implanted in 6 sheep (15 acute implants have previously been reported). The inlet cannula was placed in the left atrium and the outlet graft anastomosed to the descending aorta. A percutaneous cable supplied DC power and heparinized saline (10 ml/hr) for lubrication. Outputs of pump flow, stator, animal core temperature, pump power consumption, and RPM were monitored throughout the course of each experiment. The sheep moved freely within a large pen using an overhead swivel/tether system that carried all input and output lines. Four sheep survived longer than 4 weeks, and the indices of end organ function were analyzed at 28 days. No animal revealed any neurologic dysfunction. Hemoglobin was 9.075 +/- 0.78 g/dl at 28 days, as opposed to 7.475 +/- 0.68 (p = 0.002) before surgery. The blood urea nitrogen was 9.250 +/- 4.57 versus 14 +/- 5.72 mg/dl (p = 0.041), creatinine was 0.775 +/- .10 versus 0.775 +/- 0.05 mg/dl (p > or = 0.999), total bilirubin was 0.425 +/- 0.2 versus 0.225 +/- 0.05 mg/dl (p = 0.092), serum glutamic oxaloacetic transaminase was 74.75 +/- 24 versus 106.25 +/- 15.84 IU/L (p = 0.015), serum glutamic pyruvic transaminase was 36 +/- 28.7 versus 28.3 +/- 5.7 IU/L (p = 0.25), and total protein was 6.675 +/- 0.49 versus 5.47 +/- 0.15 g/dl (p = 0.025). It is concluded that these animals adapted very well to pulseless circulatory support. The results of these studies support the concept of an inexpensive, implantable, centrifugal pump as a ventricular assist device.