A comprehensive evaluation of hemodynamic energy production and circuit loss using four different ECMO arterial cannulae.

OBJECTIVE: Pulsatile-flow veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has shown encouraging results for microcirculation resuscitation and left ventricle unloading in patients with refractory cardiogenic shock. We aimed to comprehensively assess different V-A ECMO parameters and their contribution to hemodynamic energy production and transfer through the device circuit. METHODS: We used the i-cor® ECMO circuit, which composed of Deltastream DP3 diagonal pump and i-cor® console (Xenios AG), the Hilite 7000 membrane oxygenator (Xenios AG), venous and arterial tubing and a 1 L soft venous pseudo-patient reservoir. Four different arterial cannulae (Biomedicus 15 and 17 Fr, Maquet 15 and 17 Fr) were used. For each cannula, 192 different pulsatile modes were investigated by adjusting flow rate, systole/diastole ratio, pulsatile amplitudes and frequency, yielding 784 unique conditions. A dSpace data acquisition system was used to collect flow and pressure data. RESULTS: Increasing flow rates and pulsatile amplitudes were associated with significantly higher hemodynamic energy production (both p < 0.001), while no significant associations were seen while adjusting systole-to-diastole ratio (p = 0.73) or pulsing frequency (p = 0.99). Arterial cannula represents the highest resistance to hemodynamic energy transfer with 32%-59% of total hemodynamic energy generated being lost within, depending on pulsatile flow settings used. CONCLUSIONS: Herein, we presented the first study to compare hemodynamic energy production with all pulsatile ECLS pump settings and their combinations and widely used yet previously unexamined four different arterial ECMO cannula. Only increased flow rate and amplitude increase hemodynamic energy production as single factors, whilst other factors are relevant when combined.

Comparative analysis of novel esophageal pressure monitoring catheters versus commercially available alternatives in a biomechanical model of the thoracic cavity.

Transpulmonary pressure can be estimated using esophageal balloon (EB) catheters, which come in a variety of manufacturing configurations. We assessed the performance of novel polyurethane EB designs, Aspisafe NG and NG+, against existing alternatives. We created a biomechanical model of the chest cavity using a plastic chamber and an ex-vivo porcine esophagus. The chamber was pressurized (- 20 and + 20 cmH2O) to simulate pleural pressures. We conducted tests with various EB inflation volumes and measured transesophageal pressure (TEP). TEP measurement was defined as accurate when the difference between pressure within the EB and chamber was 0 ± 1 cmH2O. We computed the minimal (Vaccuracy-min) and maximal (Vaccuracy-max) EB inflation volumes of accuracy. Inflation volumes were further validated using a surrogate method derived by the clinically validated positive pressure occlusion test (PPOT). When the esophageal balloons were filled with inflation volumes within the range provided by the manufacturers, the accuracy of TEP measurements was marginal. Our tests found median Vaccuracy-min across EB of 0.00-0.50 mL (p = 0.130), whereas Vaccuracy-max ranged 0.50-2.25 mL (p = 0.002). Post PPOT validation, median TEP was - 0.4 cmH2O (- 1.5 to 0.3) (p < 0.001 among catheters). The Aspisafe NG and NG+ were accurate in 81.7% and 77.8% of the measurements, respectively. We characterized two new EBs, which demonstrated good benchtop accuracy in TEP measurements. However, accuracy was notably influenced by the precise selection of EB inflation volumes.

Ventricular Flow Dynamics With an Intra-Ventricular Balloon Pump: An In Vitro Analysis.

Due to the high treatment costs associated with durable ventricular assist devices, an intra-ventricular balloon pump (IVBP) was developed to provide low-cost, short-term support for patients suffering from severe heart failure. It is imperative that intraventricular flow dynamics are evaluated with an IVBP to ensure stagnation points, and potential regions for thrombus formation, are avoided. This study used particle image velocimetry to evaluate flow patterns within the left ventricle of a simulated severe heart failure patient with IVBP support to assess left ventricle pulsatility as an indicator of the likelihood of flow stasis. Two inflation timings were evaluated against the baseline severe heart failure condition: IVBP co-pulsation and IVBP counter-pulsation with respect to ventricular systole. IVBP co-pulsation was found to have a reduced velocity range compared to the severe heart failure condition (0.44 m/s compared to 0.54 m/s). IVBP co-pulsation demonstrated an increase in peak velocities (0.25 m/s directed toward the aortic valve during systole, as opposed to 0.2 m/s in severe heart failure), indicating constructive energy in systole and cardiac output (1.7 L/min increase with respect to severe heart failure baseline - 3.5 L/min) throughout the cardiac cycle. IVBP counter-pulsation, while exhibiting the greatest peak systolic velocity directed to the aortic valve (0.4 m/s) was found to counterasct the natural vortex flow pattern during ventricular filling, as well as inducing a secondary ventricular pulse during diastole and a 23% increase in left ventricle end-diastolic volume (indicative of dilation). Ideal IVBP actuation timing did not result in reduced intraventricular pulsatility, indicating promising blood washout.

Mitigation effect of cell exclusion on blood damage in spiral groove bearings.

Cell exclusion in spiral groove bearing (SGB) excludes red blood cells from high shear regions in the bearing gaps and potentially reduce haemolysis in rotary blood pumps. However, this mechanobiological phenomenon has been observed in ultra-low blood haematocrit only, whether it can mitigate blood damage in a clinically-relevant blood haematocrit remains unknown. This study examined whether cell exclusion in a SGB alters haemolysis and/or high-molecular-weight von Willebrand factor (HMW vWF) multimer degradation. Citrated human blood was adjusted to 35 % haematocrit and exposed to a SGB (n = 6) and grooveless disc (n = 3, as a non-cell exclusion control) incorporated into a custom-built Couette test rig operating at 2000RPM for an hour; shearing gaps were 20, 30, and 40 µm. Haemolysis was assessed via spectrophotometry and HMW vWF multimer degradation was detected with gel electrophoresis and immunoblotting. Haemolysis caused by the SGB at gaps of 20, 30 and 40 µm were 10.6 ± 3.3, 9.6 ± 2.7 and 10.5 ± 3.9 mg/dL.hr compared to 23.3 ± 2.6, 12.8 ± 3.2, 9.8 ± 1.8 mg/dL.hr by grooveless disc. At the same shearing gap of 20 µm, there was a significant reduced in haemolysis (P = 0.0001) and better preserved in HMW vWF multimers (p < 0.05) when compared SGB to grooveless disc. The reduction in blood damage in the SGB compared to grooveless disc is indicative of cell exclusion occurred at the gap of 20 µm. This is the first experimental study to demonstrate that cell exclusion in a SGB mitigates the shear-induced blood damage in a clinically-relevant blood haematocrit of 35 %, which can be potentially utilised in future blood pump design.

Investigation of heparin-loaded poly(ethylene glycol)-based hydrogels as anti-thrombogenic surface coatings for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO), a critical life-sustaining tool, faces significant challenges for the maintenance of normal haemostasis due to the large volume of circulating blood continuously in contact with artificial surfaces, hyperoxia and excessive shear stresses of the extracorporeal circuit. From a biomaterials perspective, it has been hypothesised that drug eluting coatings composed of haemocompatible hydrogels loaded with an anticoagulant drug could potentially enhance the haemocompatibility of the circuit. Poly(ethylene glycol) (PEG) has been well established as a biocompatible and anti-fouling material with wide biomedical application. Unfractionated heparin is the most commonly used anticoagulant for ECMO. In the present study, the feasibility of using heparin-loaded PEG-based hydrogels as anti-thrombogenic surface coatings for ECMO was investigated. The hydrogels were synthesised by photopolymerisation using poly(ethylene glycol) diacrylate (PEGDA) as the crosslinking monomer and poly(ethylene glycol) methacrylate (PEGMA) as the hydrophilic monomer, with heparin loaded into the pre-gel solution. Factors which could affect the release of heparin were investigated, including the ratio of PEGDA/PEGMA, water content, loading level of heparin and the flow of fluid past the hydrogel. Our results showed that increased crosslinker content and decreased water content led to slower heparin release. The hydrogels with water contents of 60 wt% and 70 wt% could achieve a sustained heparin release by adjusting the ratio of PEGDA/PEGMA. The anticoagulation efficacy of the released heparin was evaluated by measuring the activated clotting time of whole blood. The hydrogels with desirable heparin release profiles were prepared onto poly(4-methyl-1-pentene) (PMP) films with the same chemical composition as the PMP ECMO membranes. The coatings showed sustained heparin release with a cumulative release of 70-80% after 7 days. Haemocompatibility tests demonstrated that PEG hydrogel coatings significantly reduced platelet adhesion and prolonged plasma recalcification time. These results suggest that heparin-loaded PEG hydrogels are potential anti-thrombogenic coatings for ECMO.

Validated Guidelines for Simulating Centrifugal Blood Pumps.

PURPOSE: Rotary blood pumps (RBPs) employed as ventricular assist devices are developed to support the ventricles of patients suffering from heart failure. Computational Fluid Dynamics (CFD) is frequently used to predict the performance and haemocompatibility of these pumps during development, however different simulation techniques employed by various research groups result in inconsistent predictions. This inconsistency is further compounded by the lack of standardised model validation, thus it is difficult to determine which simulation techniques are accurate. To address these problems, the US Food and Drug Administration (FDA) proposed a simplified centrifugal RBP benchmark model. The aim of this paper was to determine simulation settings capable of producing accurate predictions using the published FDA results for validation. METHODS: This paper considers several studies to investigate the impact of simulation options on the prediction of pressure and flow velocities. These included evaluation of the mesh density and interface position through steady simulations as well as time step size and turbulence models (k-ε realizable, k-ω SST, k-ω SST Intermittency, RSM ω-based, SAS and SBES) using a sliding mesh approach. RESULTS: The most accurate steady simulation using the k-ω turbulence model predicted the pressure to within 5% of experimental results, however experienced issues with unphysical velocity fields. A more computationally expensive transient simulation that used the Stress-Blended Eddy Simulation (SBES) turbulence model provided a more accurate prediction of the velocity field and pressure rise to within experimental variation. CONCLUSION: The findings of the study strongly suggest that SBES can be used to better predict RBP performance in the early development phase.

Open-source automated centrifugal pump test rig.

Design methods for large industrial pumps are well developed, but they cannot be relied upon when designing specialised miniature pumps, due to scaling issues. Therefore, the design and development phase of small pumps demand numerous experimental tests to ensure a viable prototype. Of initial interest is hydraulic design in the form of pump performance and efficiency curves. This project aimed to produce an automated test rig capable of generating both the performance (P-Q - pressure vs. flow rate) and efficiency curves that are reliable and repeatable. The apparatus is largely customizable and suitable for a range of smaller pump sizes. The pump impeller and volute were 3D printed, allowing for design flexibility and rapid prototyping and testing. The test loop was automated which allowed the flow rate to be incremented from 0 L/min to the maximum flow rate. At each step the pressure, flow rate, voltage and current were recorded to generate the P - Q and efficiency curves. Repeatability results showed low variations of ±3 mmHg (400 Pa) in pressure and ± 2% in hydraulic efficiency. The given setup can be used to compare and evaluate the hydraulic performance of various pump designs.