Background: There is a need to take a broader look at nanotoxicological studies. Eventually, the field will demand that some generalizations be made. To begin to address this issue, we posed a question: are metal colloids on the nanometer-size scale a homogeneous group? In general, most people can agree that the physicochemical properties of nanomaterials can be linked and related to their induced toxicological responses. Methods: The focus of this study was to determine how a set of selected physicochemical properties of five specific metal-based colloidal materials on the nanometer-size scale -silver, copper, nickel, iron, and zinc -could be used as nanodescriptors that facilitate the grouping of these metal-based colloids. Results: The example of the framework pipeline processing provided in this paper shows the utility of specific statistical and pattern recognition techniques in grouping nanoparticles based on experimental data about their physicochemical properties. Interestingly, the results of the analyses suggest that a seemingly homogeneous group of nanoparticles could be separated into sub-groups depending on interdependencies observed in their nanodescriptors. Conclusion: These particles represent an important category of nanomaterials that are currently mass produced. Each has been reputed to induce toxicological and/or cytotoxicological effects. Here, we propose an experimental methodology coupled with mathematical and statistical modeling that can serve as a prototype for a rigorous framework that aids in the ability to group nanomaterials together and to facilitate the subsequent analysis of trends in data based on quantitative modeling of nanoparticle-specific structure-activity relationships. The computational part of the proposed framework is rather general and can be applied to other groups of nanomaterials as well.

The successful clinical applicability of rotary left ventricular assist devices (LVADs) has led to research interest in devising a total artificial heart (TAH) using two rotary blood pumps (RBPs). The major challenge when using two separately controlled LVADs for TAH support is the difficulty in maintaining the balance between pulmonary and systemic blood flows. In this study, a starling-like controller (SLC) hybridized with an adaptive mechanism was developed for a dual rotary LVAD TAH. The incorporation of the adaptive mechanism was intended not only to minimize the risk of pulmonary congestion and atrial suction but also to match cardiac demand. A comparative assessment was performed between the proposed adaptive starling-like controller (A-SLC) and a conventional SLC as well as a constant speed controller. The performance of all controllers was evaluated by subjecting them to three simulated scenarios [rest, exercise, head up tilt (HUT)] using a mock circulation loop. The overall results showed that A-SLC was superior in matching pump flow to cardiac demand without causing hemodynamic instabilities. In contrast, improper flow regulation by the SLC resulted in pulmonary congestion during exercise. From resting supine to HUT, overpumping of the RBPs at fixed speed (FS) caused atrial suction, whereas implementation of SLC resulted in insufficient flow. The comparative study signified the potential of the proposed A-SLC for future TAH implementation particularly among outpatients, who are susceptible to variety of clinical scenarios.

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The intra-aortic ventricular assist device (IntraVAD) is a miniature intra-aortic axial-flow ventricular assist device (VAD) that works in series with the left ventricle (LV) to assist the compromised heart. Previous in vitro results have shown that the IntraVAD can successfully increase coronary perfusion and offload ventricular volume by operating in reverse-rotation control (RRc) mode. The RRc mode includes forward rotation in systole and reverse rotation (RR) in diastole. It is necessary to derive a new diffuser design that can be used for the bi-directional rotation of the IntraVAD. In this work, a dual-diffuser set (DDS) was proposed to replace the conventional inducer and diffuser upstream and downstream of the pump. The DDS comprised two diffusers, located on both sides of the impeller, omitting the conventional inducer and diffuser. Different configurations of the DDS were designed and manufactured with various combinations of curved and straight blades. All configurations were initially tested in continuous flow, then in a pulsatile mock circulatory loop. A weighted normalized scalar (WNS) was proposed to comprehensively evaluate the hemodynamic effect of the DDS with different configurations. The results show that the maximum of WNS occurred when the upstream diffuser had equal numbers of curved and straight blades and the downstream diffuser had only curved blades. This indicates such a dual-diffuser design for the IntraVAD can give an optimal cardiac assistance potentially improving ventricular contractility, thereby restoring heart function.

In the development of a left ventricular assist device (LVAD), it is important to evaluate the LVAD's hemodynamic effect on the compromised left ventricle (LV) before surgical implantation. The mock circulatory loop (MCL) is widely accepted as an in vitro test platform to evaluate LVADs across a wide range of operational conditions as a way to examine how the device and the cardiovascular system interact. Unfortunately, most MCLs represent an oversimplified model of cardiac function, with disease states simulated through generalized changes in heart rate and stroke volume. Because heart failure (HF) severity varies substantially among patients, an MCL is needed that can mimic the pressure-volume loop of an individual patient. In this work, two numerical elastance models, derived from a specific pressure volume loop template, were used to control the LV simulator of the MCL to simulate different degrees of HF. The numerical elastance model was then scaled to change the slopes of the end-systolic (ESPVR) and end-diastolic (EDPVR) pressure volume relationship curves to simulate systolic and diastolic dysfunction. The resulting experimental pressure volume loops are consistent with theoretical loops, demonstrating the feasibility of creating an MCL that can be customized for the patient.

Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction. In addition, the performance of the speed modulation strategy has been assessed under different cardiovascular states, including variation in ventricular contractility and pulmonary arterial compliance. Our results indicated that the proposed pulse profile with optimised parameters (Apulse = 10000 rpm and ωmin = 3000 rpm) was able to generate pulmonary arterial pulse pressure within the physiological range (9–15 mmHg) while avoiding undesirable pump backflow under both co- and counter-pulsation modes. As compared to co-pulsation, stroke work was reduced by over 44% under counter-pulsation, suggesting that mechanical workload of the right ventricle can be efficiently mitigated through counter-pulsing the pump speed. Furthermore, our results showed that improved ventricular contractility could potentially lead to higher risk of ventricular suction and pump backflow, while stiffening of the pulmonary artery resulted in increased pulse pressure. In conclusion, the proposed speed modulation strategy produces pulsatile hemodynamics, which is more physiologic than continuous blood flow. The findings also provide valuable insight into the interaction between RVAD speed modulation and the pulmonary circulation under various cardiovascular states.

Christopher r. Broda ,* p. alex smith , † Yaxin Wang ‡; hamsini sriraman, § peter s. oWuor, ¶ luiz C. sampaio ,∥ iki adaChi,# and doris a. taYlor, **, † † Our objective was to create a bio-engineered pump (BEP) for subpulmonary Fontan circulation support capable of luminal endothelialization and producing a 2-6 mmHg pressure gradient across the device without flow obstruction. To accomplish this, porcine urinary bladder submucosa was decellularized to produce a urinary bladder matrix (UBM) which produced acellular sheets of UBM. The UBM was cultured with human umbilical vein endothelial cells producing a nearly confluent monolayer of cells with the maintenance of typical histologic features demonstrating UBM to be a suitable substrate for endothelial cells. A lamination process created bilayer UBM sheets which were formed into biologic reservoirs. BEPs were constructed by securing the biologic reservoir between inlet and outlet valves and compressed with a polyurethane balloon. BEP function was evaluated in a simple flow loop representative of a modified subpulmonary Fontan circulation. A BEP with a 92-mL biologic reservoir operating at 60 cycles per minute produced pulsatile downstream flows without flow obstruction and generated a favorable pressure gradient across the device, maintaining upstream pressure of 6 mm Hg and producing downstream pressure of 13 mm Hg. The BEP represents potential long-term assistance for the Fontan circulation to relieve venous hypertension, provide pulsatile pulmonary blood flow and maintain cardiac preload.

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