A unique data analysis framework and open source benchmark data set for the analysis of comprehensive two-dimensional gas chromatography software.

Comprehensive two-dimensional gas chromatography (GC × GC) is amongst the most powerful separation technologies currently existing. Since its advent in early 1990, it has become an established method which is readily available. However, one of its most challenging aspects, especially in hyphenation with mass spectrometry is the high amount of chemical information it provides for each measurement. The GC × GC community agrees that there, the highest demand for action is found. In response, the number of software packages allowing for in-depth data processing of GC × GC data has risen over the last couple of years. These packages provide sophisticated tools and algorithms allowing for more streamlined data evaluation. However, these tools/algorithms and their respective specific functionalities differ drastically within the available software packages and might result in various levels of findings if not appropriately implemented by the end users. This study focuses on two main objectives. First, to propose a data analysis framework and second to propose an open-source dataset for benchmarking software options and their specificities. Thus, allowing for an unanimous and comprehensive evaluation of GC × GC software. Thereby, the benchmark data includes a set of standard compound measurements and a set of chocolate aroma profiles. On this foundation, eight readily available GC × GC software packages were anonymously investigated for fundamental and advanced functionalities such as retention and detection device derived parameters, revealing differences in the determination of e.g. retention times and mass spectra.

Low bearing wear in explanted HeartMate II left ventricular assist devices after chronic clinical support.

The primary objective of this study was to evaluate bearing wear during clinical use of the HeartMate II (HMII) left ventricular assist device. Bearings obtained from HMII pumps explanted after clinical use in the Destination Therapy and Bridge to Transplantation clinical trials were analyzed for wear using surface profilometry. Geometric profile variations measured on the inlet bearing ball were used to calculate the wear. Bearing wear was normalized to the total pump support duration to obtain an annualized bearing wear rate. Bearing life was estimated assuming a linear wear rate, as the time to reach a wear limit of 25 µm, which includes a 3× safety factor, to ensure that there is no contact between the rotor blades and the blood bore housing. One hundred and eighty-three bearings from left ventricular assist devices implanted in 181 patients were analyzed. Average age of the patients was 56.3 ± 14.6 years, 76% were male, 46% had an ischemic etiology of heart failure. Mean support duration for the pumps was 363 ± 349 days (median: 238, range: 1-1,621 days). Sixty pumps (33%) were explanted at heart transplantation, 20 (11%) after device replacement, 6 (3%) for ventricular recovery, 94 (51%) after patient death, and 3 (2%) were explanted for other reasons. Mean bearing wear was 0.59 ± 0.37 µm (median: 0.46 µm [5-95% interval: 0.25-1.48]). The median bearing wear rate for patients supported for at least 1 year was 0.30 [5-95% interval: 0.09-0.94] µm/yr. The 5-95% limits of the bearing wear rate corresponded to an estimated bearing life between 27 and 269 years. The pump having the highest bearing wear rate (1.46 µm/yr) had an estimated bearing life of at least 17 years. HMII bearing wear is extremely small, with an estimated bearing life well in excess of 17 years; it is not a limiting factor for long-term support with the HMII left ventricular assistive system.

Challenges in longer-term mechanical support of fontan circulation in sheep.

Single ventricle congenital heart defects are usually palliated with the end result of a Fontan circulation. Despite improving results, this circulation is still associated with long-term failure. We previously developed an animal model of mechanical cavopulmonary circulation support that was successful in the acute and mid-term period. In the current study, we evaluated longer support durations in five Western-breed sheep. Through a right thoracotomy we instituted mechanical support from the inferior vena cava to the pulmonary artery, using a Heartmate II axial flow pump (Thoratec Corp., Pleasanton, CA). Postoperatively, the animals were anticoagulated with heparin iv. Hemodynamics, pump flow, anticoagulation, and hepatic and renal function were monitored daily. All animals survived the operation. Signs of moderate liver and kidney injury in general reversed quickly. Two animals had a fatal pump thrombosis. When anticoagulation was effective, hemodynamics and pump flow were maintained to normal values. Effective anticoagulation was difficult to achieve because of the high variability in response to heparin. Survival up to 18 days was accomplished. This study is the longest reported survival of animals with a mechanically assisted cavopulmonary circulation. The performance of the Thoratec Heartmate II has been good, but the issue of effective anticoagulation has not yet been solved.

Recovery during mid-term mechanical support of fontan circulation in sheep.

Total cavopulmonary connection (CPC) has a significant incidence of late failure due to increased systemic venous pressure and low cardiac output. Mechanical support could prevent failure by correcting hemodynamics. We established a model of inferior CPC using an axial flow pump (Thoratec HeartMate II, Thoratec Corp. Pleasanton, CA) in a group of ten 47-57 kg sheep and assessed hemodynamics and metabolism as a potential chronic treatment option for failed Fontan circulation. After pilot studies (n = 7), three animals underwent pump-supported inferior CPC to assess hemodynamic and metabolic responses. Pump inflow was connected to the inferior vena cava (IVC) and outflow to the main pulmonary artery. The IVC was ligated at the right atrium. Hemodynamic and biochemical parameters were recorded over four days. The first seven animals died from pump-related causes (graft kinking, three; pump thrombosis, one) or other causes (GI bleeding, one; suspected stroke, two). The subsequent three animals were electively euthanized on postoperative day four due to IRB requirements. Over the four day postoperative period, pump flow was 3.43 +/- 0.62 L/min and IVC pressure 4.05 +/- 3.21 mm Hg (mean +/- SD). Lactate levels remained normal. Low pressure and high-volume IVC flow was sustained by mechanical support. We will next attempt chronic pump implantation.

Models of metabolic utilization predict limiting conditions for sustained power from conditioned skeletal muscle.

Application and development of muscle powered cardiac assist devices is limited by the ability to predict the sustainable power output of in situ conditioned muscle under the expected loading conditions and geometrical constraints. Empirical definition of the sustained power limits and representative models of the bounding conditions where continuous power can be obtained are needed for device design and optimization. The latissimus dorsi muscles of four goats were chronically conditioned for 11 weeks with an implanted myostimulator. The ability to sustain power under isotonic conditions was evaluated across a range of contraction durations (100-600 ms) and rates (10-120 contractions/min). Muscles were characterized both biomechanically and myothermically to develop and evaluate three increasingly complex empirically-based models of metabolic utilization per contraction based on (1) the duty cycle, (2) a linear function of activation time, and (3) a multivariate-derived function of contraction duration, muscle load, and shortening distance. A clearly defined boundary for sustainable stimulation conditions was observed and was best represented by the linear metabolic model. These data provide both an empirical measure of chronically sustainable muscle power and predictive metabolic models that may be used to optimize the power harnessed for skeletal muscle actuated devices.

Mechanical support of total cavopulmonary connection with an axial flow pump.

OBJECTIVE: Even under optimal circumstances, total cavopulmonary connection is associated with a continuous late risk of death. Hemodynamics are distinctly abnormal, with increased systemic venous pressures and frequent low cardiac output. Our study uses a sheep model of total cavopulmonary connection to test the response to axial flow pump (Thoratec HeartMate II; Thoratec Corporation (Pleasanton, Calif)) support of total cavopulmonary connection, which might be suitable to treat patients with failing Fontan circulation. METHODS: Eight sheep (42-48 kg) were studied. After pilot studies in 3 animals, 5 underwent both pump-supported and nonsupported total cavopulmonary connection in alternating sequence for up to 2 hours. This was achieved with a 12-mm polytetrafluoroethylene graft from the (distally ligated) superior vena cava to the main pulmonary artery and a cannula placed in the inferior vena cava with an attached 16-mm Dacron graft to the main pulmonary artery. Pressures (arterial, inferior vena cava, left atrium, and pulmonary artery) and flows (ascending aorta and inferior vena cava) were recorded over 1 hour both with unsupported total cavopulmonary connection and after placing an axial flow pump (Thoratec HeartMate II) between the inferior vena caval inflow cannula and the main pulmonary artery. RESULTS: Under nonsupported total cavopulmonary connection circulation, inferior vena caval and aortic blood flow decreased by nearly 50%. Inferior vena caval pressure nearly doubled, whereas arterial pressure decreased by one third. Pulmonary artery pressure became nonpulsatile; however, mean pulmonary artery pressure and left atrial pressure did not change significantly. With pump-supported Fontan circulation, cardiac output, inferior vena caval flow, and arterial pressure returned to baseline. Inferior vena caval pressure decreased to below baseline levels. Mean pulmonary artery pressure and left atrial pressure again remained unchanged. CONCLUSIONS: Axial flow pump support from the inferior vena cava to the pulmonary artery can prevent the substantial decrease of aortic flow and pressure associated with total cavopulmonary connection and can reverse its poor hemodynamics. This is a simple model that can be used to further evaluate the potential of mechanical support as a treatment option in failing Fontan circulation.