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Stroke has become the main cause of mortality and morbidity in patients treated with Left Ventricular Assist Devices (LVADs). The hemodynamics of the left ventricle are altered by the implantation of an LVAD, with the increase of thrombogenic flow patterns, such as stagnation regions. Time-resolved stereo particle image velocimetry (Stereo-PIV) measurements of the flow inside a patient-specific model of the left ventricle (LV) implanted with an LVAD were performed. The effects of LVAD speed, peripheral resistance and afterload were investigated. The impact of activating the LVAD pulsatility mode (periodic speed modulation) was also evaluated. Analysis of the velocity measurements in two orthogonal planes revealed stagnation zones which may be favorable to thrombus formation. Increasing LVAD speed, despite increasing the flow rate through the inflow cannula, does not automatically result in smaller stagnation regions. These results demonstrated the strong interdependence of peripheral resistance, afterload and flow through the LVAD. As a consequence, the pulsatility mode showed very limited effect on overall flow rate. However, it did reduce the size of high stagnation areas. This study showed how LVAD speed, peripheral resistance and afterload impact the complex intraventricular flow patterns in a ventricle implanted with an LVAD and quantify their thrombogenic risk.

Two passive blade pitch control strategies for an axial-flow current turbine were developed and tested experimentally in a recirculating flume. The goal of the control is to regulate mechanical power, while limiting rotor loads, when flow conditions exceed the rated condition. Both strategies use blades fabricated with unidirectional carbon fiber oriented off-axis, such that the blades twist passively as they deflect in response to loading. One control strategy combines passive adaptive blades with overspeed control (operating at a rotational speed above the tip-speed ratio corresponding to peak efficiency) while the other combines passive adaptive blades with active pitch control (actuating blade pitch using motors at the blade root). Both strategies were implemented with a 0.45-m diameter turbine in linearly increasing inflow from 0.7 to 0.8 m/s and compared to control strategies using rigid, aluminum blades under the same flow conditions. The passive adaptive blades combined with active pitch control saw no improvement in steady-state load reductions relative to rigid blades used with active pitch control. However, the passive adaptive blades combined with overspeed control successfully produced constant torque with an only 12% increase in thrust, relative to the rated flow condition. The flow confinement likely enhanced the relative benefit of passive adaptive blades compared to speed control strategies with rigid blades. Overall, results indicate that passive adaptive blades combined with overspeed control can be an effective strategy in currents above the rated flow speed, removing the need for an active pitch mechanism in some applications. In addition to measuring turbine loads, deflection and twist of the passive adaptive blades during experimental testing were observed using a high-speed camera to support our understanding of the bend–twist behavior during turbine operation over a range of flow speeds, rotation rates, and preset pitch angles.

Flow in sidewall cerebral aneurysms can be ideally modelled as the combination of flow over a spherical cavity and flow in a curved circular pipe, two canonical flows. Flow in a curved pipe is known to depend on the Dean number $De$, combining the effects of Reynolds number $\\textit {Re}$ and of the curvature along the pipe centreline, $\\kappa$. Pulsatility in the flow introduces a dependence on the Womersley number $Wo$. Using stereo particle image velocimetry measurements, this study investigated the effect of these three key non-dimensional parameters, by modifying pipe curvature ($De$), flow rate ($Re$) and pulsatility frequency ($Wo$), on the flow patterns in a spherical cavity. A single counter-rotating vortex was observed in the cavity for all values of pipe curvature $\\kappa$ and Reynolds number $\\textit {Re}$, for both steady and pulsatile inflow conditions. Increasing the pipe curvature impacted the flow patterns in both the pipe and the cavity, by shifting the velocity profile towards the cavity opening and increasing the flow rate in to the cavity. The circulation in the cavity was found to collapse well with only the Dean number, for both steady and pulsatile inflows. For pulsatile inflow, the counter-rotating vortex was unstable and the location of its centre over time was impacted by the curvature of the pipe, as well as $\\textit {Re}$ and $Wo$ in the free stream. The circulation in the cavity was higher for steady inflow than for the equivalent average Reynolds number and Dean number pulsatile inflow, with very limited impact of the Womersley number in the range studied. A second part of this study, that focuses on the changes in fluid dynamics when the intracranial aneurysm is treated with a flow-diverting stent, can be found in this issue (Barbour et al., J. Fluid Mech., vol. 915, 2021, A124).

Cell motility plays an essential role in many biological systems, but precise quantitative knowledge of the biophysical processes involved in cell migration is limited. Better measurements are needed to ultimately build models with predictive capabilities. We present an improved force cytometry method and apply it to the analysis of the dynamics of the chemotactic migration of the amoeboid form of Dictyostelium discoideum. Our explicit calculation of the force field takes into account the finite thickness of the elastic substrate and improves the accuracy and resolution compared with previous methods. This approach enables us to quantitatively study the differences in the mechanics of the migration of wild-type (WT) and mutant cell lines. The time evolution of the strain energy exerted by the migrating cells on their substrate is quasi-periodic and can be used as a simple indicator of the stages of the cell motility cycle. We have found that the mean velocity of migration v and the period of the strain energy T cycle are related through a hyperbolic law v = LIT, where L is a constant step length that remains unchanged in mutants with adhesion or contraction defects. Furthermore, when cells adhere to the substrate, they exert opposing pole forces that are orders of magnitude higher than required to overcome the resistance from their environment.

The majority of utility-scale horizontal-axis current turbines use either speed or pitch control to maintain a constant power output once the currents exceed a certain threshold: the turbine-specific “rated speed”. In this study, we experimentally characterized power performance and turbine loading over a range of blade pitch settings and tip-speed ratios for a three-bladed horizontal-axis turbine. We then implemented a control strategy to maintain power output in time-varying currents using blade pitch control and compare the turbine performance under this control strategy to “overspeed” and “underspeed” control strategies for a fixed pitch turbine. The experiments were conducted with a laboratory-scale 0.45-m diameter turbine in an open channel flume with a 35% blockage ratio. During pitch characterization experiments, inflow velocity was maintained at 0.8 m/s with 4% turbulence intensity. During time-varying inflow experiments, currents varied from 0.7 to 0.8 m/s over a 20-min period, while a proportional controller regulated either blade pitch or rotor speed, and we recorded turbine power output and turbine loads. In this velocity range, where turbine performance is independent of Reynolds number, we demonstrated that pitch control substantially reduced torque requirements relative to underspeed control and turbine loads relative to overspeed control. Additional tests were conducted for underspeed control and pitch control in a Reynolds-dependent regime with time-varying inflow between 0.4–0.5 and 0.5–0.6 m/s. These cases suggest that blade pitch control could provide even greater benefits relative to speed control in small-scale applications.

ObjectivesTo study the correlation between wall shear stress and endothelial cell expression in a patient-specific, three-dimensional (3D)-printed model of a cerebral aneurysm.Materials and methodsA 3D-printed model of a cerebral aneurysm was created from a patient’s angiogram. After populating the model with human endothelial cells, it was exposed to media under flow for 24 hours. Endothelial cell morphology was characterized in five regions of the 3D-printed model using confocal microscopy. Endothelial cells were then harvested from distinct regions of the 3D-printed model for mRNA collection and gene analysis via quantitative polymerase chain reaction (qPCR.) Cell morphology and mRNA measurement were correlated with computational fluid dynamics simulations.ResultsThe model was successfully populated with endothelial cells, which survived under flow for 24 hours. Endothelial morphology showed alignment with flow in the proximal and distal parent vessel and aneurysm neck, but disorganization in the aneurysm dome. Genetic analysis of endothelial mRNA expression in the aneurysm dome and distal parent vessel was compared with the proximal parent vessels. ADAMTS-1 and NOS3 were downregulated in the aneurysm dome, while GJA4 was upregulated in the distal parent vessel. Disorganized morphology and decreased ADAMTS-1 and NOS3 expression correlated with areas of substantially lower wall shear stress and wall shear stress gradient in computational fluid dynamics simulations.ConclusionsCreating 3D-printed models of patient-specific cerebral aneurysms populated with human endothelial cells is feasible. Analysis of these cells after exposure to flow demonstrates differences in both cell morphology and genetic expression, which correlate with areas of differential hemodynamic stress.

Cardiopulmonary bypass (CPB) is required during most cardiac surgeries. CBP drives systemic inflammation and multiorgan dysfunction that is especially severe in neonatal patients. Limited understanding of molecular mechanisms underlying CPB-associated inflammation presents a significant barrier to improve clinical outcomes. To better understand these clinical issues, we performed mRNA sequencing on total circulating leukocytes from neonatal patients undergoing CPB. Our data identify myeloid cells, particularly monocytes, as the major cell type driving transcriptional responses to CPB. Furthermore, IL-8 and TNF-α were inflammatory cytokines robustly upregulated in leukocytes from both patients and piglets exposed to CPB. To delineate the molecular mechanism, we exposed THP-1 human monocytic cells to CPB-like conditions, including artificial surfaces, high shear stress, and cooling/rewarming. Shear stress was found to drive cytokine upregulation via calcium-dependent signaling pathways. We also observed that a subpopulation of THP-1 cells died via TNF-α-mediated necroptosis, which we hypothesize contributes to post-CPB inflammation. Our study identifies a shear stress-modulated molecular mechanism that drives systemic inflammation in pediatric CPB patients. These are also the first data to our knowledge to demonstrate that shear stress causes necroptosis. Finally, we observe that calcium and TNF-α signaling are potentially novel targets to ameliorate post-CPB inflammation.

Computational hemodynamic simulations of cerebral aneurysms have traditionally relied on stereotypical boundary conditions (such as blood flow velocity and blood pressure) derived from published values as patient-specific measurements are unavailable or difficult to collect. However, controversy persists over the necessity of incorporating such patient-specific conditions into computational analyses. We perform simulations using both endovascularly-derived patient-specific and typical literature-derived inflow and outflow boundary conditions. Detailed three-dimensional anatomical models of the cerebral vasculature are developed from rotational angiography data, and blood flow velocity and pressure are measured in situ by a dual-sensor pressure and velocity endovascular guidewire at multiple peri-aneurysmal locations in 10 unruptured cerebral aneurysms. These measurements are used to define inflow and outflow boundary conditions for computational hemodynamic models of the aneurysms. The additional in situ measurements which are not prescribed in the simulation are then used to assess the accuracy of the simulated flow velocity and pressure drop. Simulated velocities using patient-specific boundary conditions show good agreement with the guidewire measurements at measurement locations inside the domain, with no bias in the agreement and a random scatter of ≈25%. Simulated velocities using the simplified, literature-derived values show a systematic bias and over-predicted velocity by ≈30% with a random scatter of ≈40%. Computational hemodynamics using endovascularly measured patient-specific boundary conditions have the potential to improve treatment predictions as they provide more accurate and precise results of the aneurysmal hemodynamics than those based on commonly accepted reference values for boundary conditions.

Aims Optimal blood pressure (BP) control is imperative to reduce complications, especially strokes, in continuous flow ventricular assist device (VAD) patients. Doppler BP has been shown to be an accurate and reliable non‐invasive BP measurement method in HeartMate II and HVAD patients. We examined whether Doppler BP is also accurate in patients with the HeartMate 3 VAD. Methods and results In a prospective, longitudinal cohort of HeartMate 3 patients, arterial line BP and simultaneously measured Doppler opening pressure were obtained. Correlation and agreement between Doppler opening pressure and arterial line mean arterial pressure (MAP) versus systolic blood pressure (SBP) were analysed, as well as the effect of pulse pressure on the accuracy of Doppler opening pressure. A total of 589 pairs of simultaneous Doppler opening pressure and arterial line pressure readings were obtained in 43 patients. Doppler opening pressure had good correlation with intra‐arterial MAP (r = 0.754) and more closely approximated MAP than SBP (mean error 2.0 vs. −8.6 mmHg). Pulse pressure did not have a clinically significant impact on the accuracy of the Doppler BP method. These results in HeartMate 3 patients are very similar to previous results in HeartMate II and HVAD patients. Conclusions Doppler BP method should be the default non‐invasive BP measurement method in continuous flow VAD patients including patients implanted with the HeartMate 3.

Abstract Aims Accurate blood pressure (BP) measurement in continuous-flow ventricular assist device (CF-VAD) patients is imperative to reduce stroke risk. This study assesses the accuracy of the Doppler opening pressure method compared with the gold standard arterial line method in CF-VAD patients. Methods and results In a longitudinal cohort of HeartMate II and HVAD patients, arterial line BP and simultaneously measured Doppler opening pressure were obtained. Overall correlation, agreement between Doppler opening pressure and arterial line mean vs. systolic pressure, and the effect of arterial pulsatility on the accuracy of Doppler opening pressure were analysed. A total of 1933 pairs of Doppler opening pressure and arterial line pressure readings within 1 min of each other were identified in 154 patients (20% women, mean age 55 ± 15, 50% HeartMate II and 50% HVAD). Doppler opening pressure had good correlation with invasive mean arterial pressure (r = 0.742, P < 0.0001) and more closely approximated mean than systolic BP (mean error 2.4 vs. −8.4 mmHg). Arterial pulsatility did not have a clinically significant effect on the accuracy of the Doppler opening pressure method. Conclusions Doppler opening pressure should be the standard non-invasive method of BP measurement in CF-VAD patients.