Search

Modulation of pump speed has been proposed and implemented clinically to improve vascular pulsatility in continuous flow ventricular assist device patient. The flow dynamics of the HVAD with a promising asynchronous pump speed modulation and its potential risk for device-induced blood trauma was investigated numerically. The boundary conditions at the pump inlet and outlet were defined using the pressure waveforms adapted from the experimentally recorded ventricular and arterial pressure waveforms in a large animal ischemic heart failure (IHF) model supported by the HVAD operated at constant and modulated pump speeds. Shear stress fields and hemolysis indices were derived from the simulated flow fields. The overall features of the computationally generated flow waveforms at simulated constant and pulse-modulated speed operations matched with those of the experimentally recorded flow waveforms. The simulations showed that the shear stress field and hemolysis index vary throughout the cardiac cycle under the constant speed operation, and also as a function of modulation profile under modulated speed operation. The computational model did not demonstrate any differences in the time average hemolysis index between constant and modulated pump speed operations, thereby predicting pulse-modulated speed operation may help to restore vascular pulsatility without any further increased risk of blood trauma. Graphical abstract The streamline inside the HVAD pump and the wall shear stress distribution on the impeller surface at six discrete time instants over one cardiac cycle under constant speed operation (3000 rpm) (a) and under pulse-modulated speed operation (b). c Computationally predicted flow rate waveform under pulse-modulated speed operation. d Computationally predicted time-varying HI generated by the HVAD pump under the two operation modes constant speed (dash line) and pulse-modulated speed (solid line). These figures indicate that the pulse-modulated speed operation may help to restore vascular pulsatility without any further increased risk of blood trauma.

Mechanical circulatory support devices (MCSDs) have gained widespread clinical acceptance as an effective heart failure (HF) therapy. The concept of harnessing the kinetic energy (KE) available in the forward aortic flow (AOF) is proposed as a novel control strategy to further increase the cardiac output (CO) provided by MCSDs. A complete mathematical development of the proposed theory and its application to an example MCSDs (two-segment extra-aortic cuff) are presented. To achieve improved device performance and physiologic benefit, the example MCSD timing is regulated to maximize the forward AOF KE and minimize retrograde flow. The proof-of-concept was tested to provide support with and without KE control in a computational HF model over a wide range of HF test conditions. The simulation predicted increased stroke volume (SV) by 20% (9 mL), CO by 23% (0.50 L/min), left ventricle ejection fraction (LVEF) by 23%, and diastolic coronary artery flow (CAF) by 55% (3 mL) in severe HF at a heart rate (HR) of 60 beats per minute (BPM) during counterpulsation (CP) support with KE control. The proposed KE control concept may improve performance of other MCSDs to further enhance their potential clinical benefits, which warrants further investigation. The next step is to investigate various assist technologies and determine where this concept is best applied. Then bench-test the combination of kinetic energy optimization and its associated technology choice and finally test the combination in animals.

Non-surgical bleeding (NSB) is the most common clinical complication in heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). In this study, oxidative stress and alteration of signal pathways leading to platelet apoptosis were investigated. Thirty-one HF patients supported by CF-LVADs were divided into bleeder (n = 12) and non-bleeder (n = 19) groups. Multiple blood samples were collected at pre-implant (baseline) and weekly up to 1-month post-implant. A single blood sample was collected from healthy subjects (reference). Production of reactive oxygen species (ROS) in platelets, total antioxidant capacity (TAC), oxidized low-density lipoproteins (oxLDL), expression of Bcl-2 and Bcl-xL, Bax and release of cytochrome c (Cyt.c), platelet mitochondrial membrane potential (Δψ m), activation of caspases, gelsolin cleavage and platelet apoptosis were examined. Significantly elevated ROS, oxLDL and depleted TAC were evident in the bleeder group compared to non-bleeder group (p

Continuous-flow left ventricular assist devices (CF LVADs) are rotary blood pumps that improve mean blood flow, but with potential limitations of non-physiological ventricular volume unloading and diminished vascular pulsatility. In this study, we tested the hypothesis that left ventricular unloading with increasing CF LVAD flow increases myocardial flow normalized to left ventricular work. Healthy (n = 8) and chronic ischemic heart failure (IHF, n = 7) calves were implanted with CF LVADs. Acute hemodynamics and regional myocardial blood flow were measured during baseline (LVAD off, clamped), partial (2–4 L/min) and full (>4 L/min) LVAD support. IHF calves demonstrated greater reduction of cardiac energy demand with increasing LVAD support compared to healthy calves, as calculated by rate-pressure product. Coronary artery flows (p

The purpose of this study was to investigate the influence of non-physiological high shear stress on activation and shedding of platelet GP IIb/IIIa receptors. The healthy donor blood was exposed to three levels of high shear stresses (25, 75, 125 Pa) from the physiological to non-physiological status with three short exposure time (0.05, 0.5, 1.5 s), created by a specific blood shearing system. The activation and shedding of the platelet GPIIb/IIIa were analyzed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). In addition, platelet P-selectin expression of sheared blood, which is a marker for activated platelets, was also analyzed. The results from the present study showed that the number of activated platelets, as indicated by the surface GPIIb/IIIa activation and P-selectin expression, increased with increasing the shear stress level and exposure time. However, the mean fluorescence of GPIIb/IIIa on the platelet surface, decreased with increasing the shear stress level and exposure time. The reduction of GPIIb/IIIa on the platelet surface was further proved by the reduction of further activated platelet GPIIb/IIIa surface expression induced by ADP and the increase in GPIIb/IIIa concentration in microparticle-free plasma with increasing the applied shear stress and exposure time. It is clear that non-physiological shear stress induced a paradoxical phenomenon, in which both activation and shedding of the GPIIb/IIIa on the platelet surface occur simultaneously. This study may offer a new perspective to explain the reason of both increased thrombosis and bleeding events in patients implanted with high shear blood contacting medical devices.

A growing number of elderly patients with significant co-morbidities do not meet the inclusion criteria for conventional cardiac surgical therapies, including aortic valve replacement and mechanical circulatory support. To meet this clinical need, an aortic valve bypass (AVB) system is being developed that may be implanted using subcostal or mini-thoracotomy surgical approaches without ventricular coring or cardiopulmonary bypass. The AVB system consists of an apical left ventricular (ALV) cannula made from pyrolytic carbon, a valved conduit with a locking mechanism, and a Nitinol clip for anastomosis to the descending aorta. To define design criteria and demonstrate efficacy, ALV cannulae with different diameters (7–14 mm), number of sideholes (6–12), sidehole size (1.9–4.6 mm wide) and tip shapes (tapered, straight) were designed, fabricated, and tested. Cannula efficacy was determined by quantifying flow rates and pressure drops across the ALV cannula using steady-state and dynamic mock circulation models simulating mild, moderate and severe aortic stenosis test conditions. Blood trauma testing was conducted to demonstrate hemocompatibility using the smallest diameter (7 mm) ALV cannula prototype fabricated from pyrolytic carbon (PYC). In vitro and blood trauma testing demonstrated that (1) the 7 mm PYC cannula did not produce significant hemolysis ( 4.5 L/min for

A counterpulsation device (Symphony) that works synchronously with the native heart to provide partial circulatory support was developed to treat patients with advanced heart failure. Symphony is implanted in a ‘pacemaker pocket’ without entry into the chest, and requires timing with ECG for device filling and ejection. Surface leads are limited to short-term use due to signal distortion and lead management issues. Transvenous leads are a clinical standard for pacemakers and internal defibrillators, but increase the complexity of the implant procedure. In this study, the feasibility of using subcutaneous leads for synchronized timing of Symphony was investigated. ECG waveforms were simultaneously measured and recorded using epicardial (control) and subcutaneous (test) leads in a bovine model for 7-days (n = 6) and 14-days (n = 2) during daily activity and treadmill exercise. Landmark features and R-wave triggering detection rates for each lead configuration were calculated and compared. Lead placement, migration, durability, and infection were quantified using fluoroscopy and histopathological examination. There were 2,849 data epochs (30-s each) recorded at rest (133,627 analyzed beats) and 35 data epochs (20 min each) recorded during treadmill exercise (37,154 analyzed beats). The subcutaneous leads provided an accurate and reliable triggering signal during routine daily activity and treadmill exercise (99.1 ± 0.4% positive predictive value, 96.8 ± 1.5% sensitivity). The subcutaneous leads were also easily placed with minimal lead migration (0.5 ± 0.1 cm), damage (no fractures or failures), or infection. These findings demonstrate the feasibility of using subcutaneous leads for synchronized timing of mechanical circulatory support while offering the advantage of less invasive surgery and associated risk factors.

Numerical and experimental studies are carried out to assess the hydraulic and hemodynamic performance and the biocompatibility of a viscous impeller pump (VIP) for cavopulmonary assist in patients with a univentricular Fontan circulation. Computational fluid dynamics (CFD) predictions of impeller performance are shown to be in very good agreement with measured pressure-flow data obtained in a Fontan mock-circulation system. Additional CFD and experimental design studies intending to balance pump performance and biocompatibility with the manufacturability limitations of a percutaneous expandable impeller are also reported. The numerical models and experimental studies confirm excellent performance of the VIP with augmentation of Fontan pressure up to 35 mmHg for flow rates up to 4.5 L/min and operational speeds no higher than 5000 RPM. Scalar stress predictions on the VIP surface and laboratory hemolysis measurements both demonstrate very low hemolysis potential. The impeller designs reported offer ideal performance and can meet manufacturing tolerances of a flexible, catheter-based percutaneous expandable rotary pump.

Continuous flow (CF) left ventricular assist devices (LVAD) support diminishes vascular pressure pulsatility. Despite its recent clinical success CF LVAD support has been associated with a higher incidence of gastrointestinal bleeding, aortic valve dysfunction and hemorrhagic strokes. To overcome this limitation, we are developing algorithms to provide vascular pulsatility using a CF LVAD. The effects of timing and synchronizing the CF LVAD flow modulation to the native myocardium, modulation amplitude, and modulation widths were studied on the native ventricle and vasculature using a computer simulation model of the circulatory system simulating heart failure. A total of over 150 combinations of varying pulse widths, beat frequencies, time shifts, and amplitudes to modulate CF LVAD flow were tested. All control algorithms maintained a mean CF LVAD flow of 5.0 ± 0.1 L/min (full support) or 2.5 ± 0.1 L/min (partial support). These algorithms resulted in an increased arterial pressure pulsatility of up to 59 mmHg, reduced left ventricular external work (LVEW) by 10–75%, and increased myocardial perfusion by up to 44% from baseline heart failure condition. Importantly, reduction in LVEW and increase in pulsatility may be adjusted to user-defined values while maintaining the same average CF LVAD flow rate. These methods of CF LVAD flow modulation may enable tailored unloading of the native ventricle to provide rest and rehabilitation (maximal unloading to rest followed by gradual reloading to wean), which may promote sustainable myocardial recovery. Further, these LVAD flow modulation patterns may reduce the incidence of adverse events associated with the CF LVAD therapy by increasing vascular pulsatility.