Pulsatile Mode Research Articles

Development of in vitro microfluidic models to study endothelial responses to pulsatility with different mechanical circulatory support devices.

Continuous-flow ventricular assist devices (CFVAD) and counterpulsation devices (CPD) are used to treat heart failure (HF). CFVAD can diminish pulsatility, but pulsatile modes have been implemented to increase vascular pulsatility. The effects of CFVAD in a pulsatile mode and CPD support on the function of endothelial cells (ECs) are yet to be investigated. In this study, two in vitro microfluidic models for culturing ECs are proposed to reproduce blood pressure (BP) and wall shear stress (WSS) on the arterial endothelium while using these medical devices. The layout and parameters of the two microfluidic systems were optimized based on the principle of hemodynamic similarity to efficiently simulate physiological conditions. Moreover, the unique design of the double-pump and double afterload systems could successfully reproduce the working mode of CPDs in an in vitro microfluidic system. The performance of the two systems was verified by numerical simulations and in vitro experiments. BP and WSS under HF, CFVAD in pulsatile modes, and CPD were reproduced accurately in the systems, and these induced signals improved the expression of Ca2+, NO, and reactive oxygen species in ECs, proving that CPD may be effective in normalizing endothelial function and replacing CFVAD to a certain extent to treat non-severe HF. This method offers an important tool for the study of cell mechanobiology and a key experimental basis for exploring the potential value of mechanical circulatory support devices in reducing adverse events and improving outcomes in the treatment of HF in the future.

Turbulence suppression by cardiac-cycle-inspired driving of pipe flow.

Flows through pipes and channels are, in practice, almost always turbulent, and the multiscale eddying motion is responsible for a major part of the encountered friction losses and pumping costs1. Conversely, for pulsatile flows, in particular for aortic blood flow, turbulence levels remain low despite relatively large peak velocities. For aortic blood flow, high turbulence levels are intolerable as they would damage the shear-sensitive endothelial cell layer2-5. Here we show that turbulence in ordinary pipe flow is diminished if the flow is driven in a pulsatile mode that incorporates all the key features of the cardiac waveform. At Reynolds numbers comparable to those of aortic blood flow, turbulence is largely inhibited, whereas at much higher speeds, the turbulent drag is reduced by more than 25%. This specific operation mode is more efficient when compared with steady driving, which is the present situation for virtually all fluid transport processes ranging from heating circuits to water, gas and oil pipelines.

P77: Improvements in the cuff and graft interface of a rotary Total Artificial Heart

Purpose: To evaluate design improvements of the inlet cuff-port and outlet graft-port interface of a Total Artificial Heart (TAH) on pannus formation. The orifice size, interface, blood flow path geometry, blood flow velocity, materials, surface finish, and hematologic parameters (such as anti-coagulants and anti-platelets) all contribute to the hemocompatibility of the TAH inflow and outflow. The focus of this work is the blood flow path geometry and material change. Methods: The performance of progressive inflow and outflow design iterations of a rotary total artificial heart operated in continuous and pulsatile outflow were evaluated in Corrient calves for durations of 30-90 days. Design modifications included a smoother blood flow port transition, geometrical improvements to the diameter and tangent angle to the polyurethane connector/pump interface, and methods of securing the connection including a titanium ring on the cuff with biospan rings and PEEK zip ties on both the cuffs and grafts. The graft flow path includes a circumferential hump which allows the titanium outflow port to seat against this hump and eliminate a void which could be a source of thrombus or emboli. Additionally, the cuff and port materials were changed. Subjects were 6-12 month old calves with weights ranging from 82 kg to 108 kg, while conditions such as pump flow, pressures and anticoagulants were closely monitored. The TAH was run in pulsatile mode for the majority of the studies. At necropsy, photos of the cuff and graft interface to the pump were analyzed and any tissue samples were sent for histological evaluation. Results: A titanium ring on the cuff prevented the cuff from pulling away from the titanium port at the ostium and also prevented the cuff from being to be pulled too far onto the port during surgery. Pannus formation at the interface of the cuff and graft to the titanium ports was graded from Absent (0) to Extreme (5), (Extreme equals >75% area reduction). In earlier design iterations, pannus formation at the inflow cuff or outflow graft interface ranged from (2) mild to (5) extreme. After implementing the design improvements, pannus was (0) absent in all inflow cuff interfaces. One graft that was not fully installed on the port had moderate buildup and the remainder had (0) absent to (1) minor at the outflow graft interface despite minimal anticoagulation. Conclusion: Improvements to the inflow cuff/outflow graft-port interface significantly reduced pannus and thrombus formation in chronic animal implants treated with limited anticoagulation.

A Novel Equivalent Time Sampling-Based Method for Pulse Transit Time Estimation with Applications into the Cardiovascular Disease Diagnosis.

The increasing incidence of cardiovascular diseases (CVDs) is reflected in additional costs for healthcare systems all over the world. To date, pulse transit time (PTT) is considered a key index of cardiovascular health status and for diagnosis of CVDs. In this context, the present study focuses on a novel image analysis-based method for PTT estimation through the application of equivalent time sampling. The method, which post-processes color Doppler videos, was tested on two different setups: a Doppler flow phantom set in pulsatile mode and an in-house arterial simulator. In the former, the Doppler shift was due to the echogenic properties of the blood mimicking fluid only, since the phantom vessels are non-compliant. In the latter, the Doppler signal relied on the wall movement of compliant vessels in which a fluid with low echogenic properties was pumped. Therefore, the two setups allowed the measurement of the flow average velocity (FAV) and the pulse wave velocity (PWV), respectively. Data were collected through an ultrasound diagnostic system equipped with a phased array probe. Experimental outcomes confirm that the proposed method can represent an alternative tool for the local measurement of both FAV in non-compliant vessels and PWV in compliant vessels filled with low echogenic fluids.

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

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. 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. 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. 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.

Flows of Dense Suspensions of Polymer Particles through Oblique Bifurcating Channels: Two Continua Approach.

A two-velocity mathematical model is proposed for dense suspension flows through channel bifurcations. Equations agree with thermodynamic laws and they are suitable for both heavy and light particles. The pulsatile mode of injection of particles is considered. In the 2D-case, we address the issue of partitioning particles and study how a loss of particles into the side branch depends on the bifurcation angle. A qualitative agreement with experiment data are established. We capture the Zweifach–Fung effect. We treat polymer particles as a phase enjoying the rheology of the Bingham viscoplastic material. We prove that the polymer particle distribution between two branches correlates with the averaged-in-time Bingham number in these branches.

The CorWave LVAD - Synchronized Pulsatility with Improved Hemodynamics

<h3>Purpose</h3> The CorWave LVAD employs a novel wave membrane technology to generate low shear blood propulsion that can produce a physiologic pulse. Herein, we report the results of in vitro and in vivo testing of pumps for hemodynamics, hemocompatibility, and durability. <h3>Methods</h3> Computational simulations were used to optimize shear stress in the blood flow path < 9 dyn/cm², the maximum that occurs in normal physiology, while improving hydraulic performance. Prototype pumps confirmed the hydraulic and hemocompatibility results with the optimized flow paths. Pulsatility control algorithms were tested for sensorless synchronization with the native left ventricle (LV), arrhythmia detection, and pulse pressure (PP) amplitude generation in 3 settings: 1) In vitro mock circulation loops (MCLs), 2) acute implants in sheep with induced heart failure (HF), and 3) chronic implants in healthy sheep. An adaptive pump control program was developed to adjust the pump operating settings in response to changes in pre-load or after-load. Pump durability was assessed by continuous operation in MCLs. <h3>Results</h3> During implants in sheep with HF (EF 20-40%), the cardiac output increased from a baseline of 2-3 LPM to 5-6 LPM with the CorWave LVAD operating in continuous and pulsatile modes. The pulsatility algorithm successfully synchronized to > 95% of LV contractions during acute and chronic implants without the use of sensors. The algorithm identified arrhythmia conditions for safe transitions to non-synchronized operating modes. CorWave pumps generated PPs > 30 mmHg in vitro, and > 25 mmHg in vivo, where PP was constrained due to limitations of the animal model. In vivo, the adaptive pump control program successfully adjusted the pump operating points in response to hemodynamic challenges. The pump hemocompatibility was confirmed by low hemolysis and preservation of von Willebrand Factor function during chronic implants. Three pumps have completed 1 year durability tests, with 7 additional devices running beyond 6 months. We are building lifecycle test stands to commence multiple year durability tests to support clinical trial submissions. <h3>Conclusion</h3> The CorWave LVAD has achieved milestones for pulsatile hemodynamic performance, hemocompatibility, and durability, demonstrating substantial progress towards clinical readiness, providing a credible alternative to rotary blood pumps.

The roles of kisspeptin and neurokinin B in GnRH pulse generation in humans, and their potential clinical application.

The delivery of gonadotropin-releasing hormone (GnRH) in a pulsatile mode to the gonadotropes has long been known to be essential for normal reproductive function. There have been numerous studies aimed at dissecting out the mechanisms underlying GnRH pulse generation. The discovery of kisspeptin as an upstream regulator of GnRH attracted the possibility that pulsatile kisspeptin governed the pulsatile secretion of GnRH. Subsequent studies have shown the importance of the neurokinin B (NKB) system in modulating kisspeptin secretion and this GnRH. A number of studies in laboratory rodents have supported this notion. By contrast, we present data from clinical studies in men and women, in a range of contexts, showing that continuous infusion of kisspeptin 10 at receptor-saturating levels gives rise to an increase in luteinizing hormone (LH) (GnRH) pulse frequency. This has been demonstrated in normal healthy and hypogonadal men, in normal women during the mid-cycle LH surge, in men and women with mutations in the genes encoding NKB or its receptor, neurokinin 3 receptor (NK3R), in women with polycystic ovary syndrome treated with NK3R antagonist, and in women treated with NK3R antagonist during the LH surge. These finds indicate that pulsatile secretion and action of kisspeptin on GnRH neurons is not required for the generation of LH (GnRH) pulses in humans. We also report that there is an absence of desensitization in humans exposed to continuous infusion of kisspeptin-10 at receptor-saturating concentrations over 22h and briefly review GnRH, kisspeptin and NKB analogs and their clinical application.

Effects of Pulsatile and Non-Pulsatile Perfusion On Oxygenator Fibers During Pediatric Cardiopulmonary Bypass

In cardiopulmoner operations patients can be perfused with a pulsatile or nonpulsatile pump mode. The extra energy maintained by the pulsatile perfusion may have different effects on the patient and the oxygenator fiber rather than nonpulsatile perfusion. Especially the effect of pulsatile perfusion on the fibers isn’t clearly known. The purpose of this study is to investigate the effects of pulsatile and non-pulsatile blood flows on oxygenator fibers. 18 out of 32 patients that had an pediatric open heart surgery was chosen according to their aortic clamp times. 9 of 18 patients were perfused in a pulsatile mode, other 9 patients were perfused in a nonpulsatile mode. The patient blood was collected before the open heart surgery (T1), before aortic clamp (T2), after aortic clamp (T3), after 1st intensive care hour (T4) and after the 1st intensive care day (T5) in order to compare the results of whole blood and plasma proteins. At the end of the open heart operation 10 cm of oxygenator fiber was removed from the fiber bundle and taken into the phosfate buffer saline (PBS) solution after the patient had a stabile outcome. Whole blood and micro protein measurements were applied in both first fiber solution and sonicated solution. No harmful effect of pulsatile perfusion on blood cells and proteins was observed according to patient results. More blood cell aggregation and total protein adsorption was observed in nonpulsatile mode fibers results. In this study pulsatile perfusion maintained better blood compability over nonpulsatile perfusion and the extra energy in pulsatile perfusion caused better microcirculation.

Relationship between Passive and Active Pulsations of Rat Artery as Vascular Extension of Frank-Starling Law.

The experiments on narcotized male rats (n=30) determined the parameters of passive and active pulsatile modes of isolated segment of femoral artery in situ. Rheographic elasticity (RE) and reactivity (RR) were correspondingly determined as the ratios of peak-to-peak (p2p) magnitudes of passive and active pulsatile oscillations of arterial electroimpedance (AEI) to p2p magnitude of BP undulations. The medians and interquartile ranges of RE and RR were 6 (3; 11) and 70 (40; 110) mΩ/mm Hg, respectively. The maximal and minimal values of RE and RR in various rats differed by 50 and 80 times, respectively, and were bimodally distributed: in major group (n=23), the values were RE<15 and RR<200 mΩ/mm Hg, whereas in minor group (n=7), these parameters were RE>20 and RR>300 mΩ/mm Hg. The above ranges of RE and RR parameters were considered as the diagnostic signs of normal and pseudo-healthy rats with pathologically augmented AEI oscillations, respectively. Statistical analysis of all rats (n=30) revealed the positive correlation between RE and RR (r=0.76) with linear regression RR=31+7.6×RE. It is hypothesized that this correlation is underlain by a mechanism similar to that described by the Frank-Starling law for myocardium.

Hemodynamic performance of a compact centrifugal left ventricular assist device with fully magnetic levitation under pulsatile operation: An in vitro study.

Long-term using continuous flow ventricular assist devices could trigger complications associated with diminished pulsatility, such as valve insufficiency and gastrointestinal bleeding. One feasible solution is to produce pulsatile flow assist with speed regulation in continuous flow ventricular assist devices. A third-generation blood pump with pulsatile operation control algorithm was first characterized alone under pulsatile mode at various speeds, amplitudes, and waveforms. The pump was then incorporated in a Mock circulation system to evaluate in vitro hemodynamic effects when using continuous and different pulsatile operations. Pulsatility was evaluated by surplus hemodynamic energy. Results showed that pulsatile operations provided sufficient hemodynamic assistance and increased pulsatility of the circulatory system (53% increment), the mean aortic pressure (65% increment), and cardiac output (27% increment). The pulsatility of the system under pulsatile operation support was increased 147% compared with continuous operation support. The hemodynamic performance of pulsatile operations is susceptible to phase shifts, which could be a tacking angle for physiological control optimization. This study found third-generation blood pumps using different pulsatile operations for ventricular assistance promising.

Взаимосвязь пассивных и активных пульсаций артерии крысы как обобщение закона Франка—Старлинга для кровеносных сосудов

The experiments on narcotized male rats (n=30) determined the parameters of passive and active pulsatile modes of isolated segment of femoral artery in situ. Rheographic elasticity (RE) and reactivity (RR) were correspondingly determined as the ratios of peak-to-peak (p2p) magnitudes of passive and active pulsatile oscillations of arterial electroimpedance (AEI) to p2p magnitude of BP undulations. The medians and interquartile ranges of RE and RR were 6 (3; 11) and 70 (40; 110) mΩ/mm Hg, respectively. The maximal and minimal values of RE and RR in various rats differed by 50 and 80 times, respectively, and were bimodally distributed: in major group (n=23), the values were RE 20 and RR>300 mΩ/mm Hg. The above ranges of RE and RR parameters were considered as the diagnostic signs of normal and pseudo-healthy rats with pathologically augmented AEI oscillations, respectively. Statistical analysis of all rats (n=30) revealed the positive correlation between RE and RR (r=0.76) with linear regression RR=31+7.6×RE. It is hypothesized that this correlation is underlain by a mechanism similar to that described by the Frank-Starling law for myocardium.

Haemodynamic evaluation of the new pulsatile-flow generation method in vitro.

Continuous-flow ventricular-assist devices are widely used to support patients with advanced heart failure, because continuous-flow ventricular-assist devices are more durable, have smaller sizes and have better survival rates for patients compared to the pulsatile-flow ventricular-assist devices. Nevertheless, continuous-flow ventricular-assist devices often cause complications such as gastrointestinal bleeding, haemorrhagic stroke, and aortic insufficiency and have a negative impact on the microcirculation for both long-time implantable and short-time extracorporeal systems. The aim of this study is the evaluation of the pulsatile-flow generation method in continuous-flow ventricular-assist device without pump speed changes. The method may be used for short-time extracorporeal continuous-flow mechanical circulatory support and long-time implantable mechanical circulatory support. A shunt with a controlled adjustable valve, that clamps periodically, is connected in parallel to the continuous-flow ventricular-assist device. We compared the continuous-flow ventricular-assist device operating with and without the shunt on the mock circulation loop. The continuous-flow ventricular-assist device-shunt system was connected according to the left ventricle-aorta circuit and worked in phase with the ventricle. Heart failure was simulated on the mock circulation circuit. Rotaflow (Maquet Inc.) was used as the continuous-flow pump. Haemolysis studies of the system for generating a pulse flow were carried out at a flow rate of 5 L/min and a pressure drop of 100 mm Hg. To compare the haemodynamic efficiency, we used the aortic pulsation index Ip, the equivalent energy pressure and the surplus haemodynamic energy. These indexes were higher in the pulsatile mode (Ip - 4 times, equivalent energy pressure by 7.36% and surplus haemodynamic energy - 10 times), while haemolysis was the same. The normalised index of haemolysis was 0.0015 ± 0.001. The results demonstrate the efficiency of the pulsatile-flow generation method for continuous-flow ventricular-assist devices without impeller rotation rate changes.

Sound analysis of the magnetically levitated left ventricular assist device HeartMate 3™.

The HeartMate 3™ has shown lower rates of adverse events compared to previous devices due to the design and absence of mechanical bearings. For previous devices, sound analysis emerged as a way to assess pump function. The aims of this study were to determine if sound analysis can be applied to the HeartMate 3 in vivo and in vitro and to evaluate an electronic stethoscope. Sound recordings were performed with microphones and clinical accessible electronic stethoscope. The recordings were studied in both the time and the frequency domains. Recordings from four patients were performed to determine if in vivo and in vitro recordings are comparable. The results show that it is possible to detect sound from HeartMate 3 and the sound spectrum is clear. Pump frequency and frequency of the pulsatile mode are easily determined. Frequency spectra from in vitro and in vivo recordings have the same pattern, and the major proportion (96.7%) of signal power is located at the pump speed frequency ±40 Hz. The recordings from the patients show low inter-individual differences except from location of peaks originating from pump speed and harmonics. Electronic stethoscopes could be used for sound recordings, but the dedicated equipment showed a clearer sound spectrum. The results show that acoustic analysis can also be performed with the HeartMate 3 and that in vivo and in vitro sound spectrum is similar. The frequency spectra are different from previous devices, and methods for assessing pump function or thrombosis need further evaluation.

Domestic ruminants as models for the elucidation of the mechanisms controlling ovarian follicle development in humans

It is necessary to understand the basic physiology underlying the complex process of folliculogenesis to address common causes of infertility and to devise innovative strategies to increase the efficiency of assisted reproduction technologies. Availability of suitable ovarian tissue is a major constraint to research in this area in humans, and monovulatory domestic ruminants represent a physiologically relevant model to elucidate basic mechanisms before more focused clinical investigations. This paper reviews the development of several whole animal and cell culture models in ruminants that have allowed basic investigations into the endocrine and local mechanisms regulating preantral and antral follicle development in monovulatory species. Studies on preantral follicle development using the ovarian autograft model have shown, contrary to accepted dogma, that FSH may mediate the rate at which preantral follicles grow and have provided evidence to support the existence of local regulatory feedback mechanisms that influence the rate of primordial follicle initiation and preantral follicle development. Studies on the endocrine control of antral follicle development using the GnRH-antagonist model have shown that a pulsatile mode of LH delivery is not a requirement for normal patterns of follicle development and ovarian hormone secretion. Studies on the local control of somatic cell differentiation using physiological cell culture models have highlighted the essential relationship between somatic cell communication and expression of ditferentiative markers. We conclude that the domestic ruminant represents a valuable model system for the elucidation of the endocrine and local mechanisms controlling both early and terminal stages of follicle development in monovulatory species. The results of these investigations have direct strategic relevance within clinical medicine.

Novel concepts about normal sexual differentiation of reproductive neuroendocrine function and the developmental origins of female reproductive dysfunction: the sheep model

The neuroendocrine regulation of GnRH secretion plays a central role in timing gamete release in both sexes. This regulation is more complex in the female because the discontinuous release of ova is more complex than the continuous release of spermatozoa. This review provides an evolving understanding of the sex differences in reproductive neuroendocrine controls and how these differences arise. The rules for sexual differentiation of steroid feedback control of GnRH secretion conceptually parallel the well-established principles that underlie the sexual differentiation of the internal and external genitalia. In the context of the neuroendocrine regulation of the ovarian cycle, and using the sheep as a model, four steroid feedback controls for GnRH secretion are inherent (default). They require no ovarian developmental input to function appropriately during adulthood. Two steroid feedback controls regulate the preovulatory surge mode of GnRH secretion, and two regulate the pulsatile mode. If the individual is a male, three steroid feedback controls of GnRH secretion become unnecessary or irrelevant, and these are abolished or become functionally inoperative through programmed reductions in hypothalamic sensitivity. This central programming occurs through exposure of presynaptic GnRH neurons in the developing male brain to the androgenic and estrogenic actions of testicular steroids. In precocial species such as ruminants, this programming begins well before birth. Understanding how GnRH secretion normally becomes sexually differentiated is of practical importance to determining how inappropriate hormonal environments during development can variously malprogram the neuroendocrine system to produce a variety of reproductive dysfunctions relating to patterning of gonadotropin secretion.

Getting Past the Spin: The CorWave LVAD, a Membrane Wave Pump Providing Physiologic Pulsatility without High Shear

Purpose A new LVAD is under development which employs a completely novel pumping technology. Magnetically driven oscillation of a polymer membrane creates a wave motion, gently pushing the blood through the pump. By changing the oscillation frequency and magnitude, pressure generation and blood flow rates can be dynamically adjusted over timescales as short as 30 msec. This approach offers a less damaging method for efficiently pumping blood while generating physiologic pulsatility. We evaluated pump actuation parameters and control algorithms in mock circulation loops and an acute animal study to evaluate and optimize pulse generation. Methods The LVAD was evaluated on a physiologic mock-loop to determine the optimal performance parameters. Pulsatility is created by switching rapidly between levels of pump output. A period of high output was generated following detection of systole to augment native cardiac output. Pump flow was reduced during diastole to avoid suck-down of the ventricle and limit back flow. The initial target was pump generated aortic dP/dt of >400 mmHg/sec under heart failure conditions with pump flow of 3-6 LPM. In parallel, hemolysis was measured using porcine blood. The pulsatility algorithm was evaluated with the pump implanted in an ovine model to validate the systole detection method. Results Evaluation on the mock circulatory loop achieved a high degree of pulsatility, defined as delta AoP=40mmHg, dP/dt=410mmHg/s, AoF=4.7 lpm, MAP=83mmHg vs. heart failure model of delta AoP=28mmHg, dP/dt=430mmHg/s, AoF=3.7lpm, MAP= 67mmHg. Generation of free hemoglobin at both high and low operating points are in a clinically acceptable range and well controlled transition between the two points does not significantly increase hemolysis. The acute animal study, the pulsatility algorithm correctly detected systole in >90% of beats. Conclusion Bench testing indicated that the pump provided augmented pulsatility to the failing heart, while achieving targeted levels of aortic flow and pressure without increased hemoglobin release. Augmented pulsatility offers a new mechanism to reduce bleeding and renal complications of VAD therapy with the intriguing possibly to increase cardiac recovery. Studies are underway to further evaluate the pulsatile operating mode algorithms and related hemoglobin release in an ovine heart failure model.

Corwave LVAD Development Update

Purpose The Corwave Neptune LVAD is being developed to employ gentle oscillation of a membrane to propel blood, based on the wave motion of swimming fish. The pump output can be readily tuned by adjusting membrane oscillation frequency and magnitude. The purpose of this project was increase the hydraulic efficiency, implement a physiologic pulsatility control algorithm, and confirm performance in animal implants. Methods The fluid path of the pump was simulated by Fluid-Structure-Interaction (FSI) computational fluid dynamic analysis in COMSOL. Membrane size, oscillation frequency, oscillation magnitude, and the blood flow path were modeled and refined to improve hydraulic performance and eliminate areas of flow stagnation. Pumps were then tested in blood analogs and blood in mock circulation loops and in vitro hemolysis testing. Non-hermetic pumps were implanted in a total of 25 sheep for acute and chronic implants. Results Design simulations and individual component testing resulted in a pump which can generate 6+ LPM of blood flow against physiologic pressures with maximum shear rates orders of magnitude lower that those of rotary blood pumps. Mock loop testing demonstrated the pumps have “flat” HQ (pressure vs. flow) curves. Three control methods were developed: fixed, asynchronous pulsatile, and synchronous pulsatile. Pulsatile modes generated dP/dt>400 mmHg/sec using sensorless detection of native ventricle systole. Animal implants demonstrated low hemolysis and an absence of renal infarcts, but were limited to about a week in duration due to the non-hermetic sealing of the pumps. Conclusion Application of robust computational simulation and bench top testing have produced a unique new kind of VAD, offering the flow capacity and reliability of rotary pumps, but adding physiologically relevant pulsatility without excessive shear rates. Future efforts will implement full hermeticity to extend animal study durations and confirm von Willebrand Factor compatibility. The Corwave Neptune LVAD is being developed to employ gentle oscillation of a membrane to propel blood, based on the wave motion of swimming fish. The pump output can be readily tuned by adjusting membrane oscillation frequency and magnitude. The purpose of this project was increase the hydraulic efficiency, implement a physiologic pulsatility control algorithm, and confirm performance in animal implants. The fluid path of the pump was simulated by Fluid-Structure-Interaction (FSI) computational fluid dynamic analysis in COMSOL. Membrane size, oscillation frequency, oscillation magnitude, and the blood flow path were modeled and refined to improve hydraulic performance and eliminate areas of flow stagnation. Pumps were then tested in blood analogs and blood in mock circulation loops and in vitro hemolysis testing. Non-hermetic pumps were implanted in a total of 25 sheep for acute and chronic implants. Design simulations and individual component testing resulted in a pump which can generate 6+ LPM of blood flow against physiologic pressures with maximum shear rates orders of magnitude lower that those of rotary blood pumps. Mock loop testing demonstrated the pumps have “flat” HQ (pressure vs. flow) curves. Three control methods were developed: fixed, asynchronous pulsatile, and synchronous pulsatile. Pulsatile modes generated dP/dt>400 mmHg/sec using sensorless detection of native ventricle systole. Animal implants demonstrated low hemolysis and an absence of renal infarcts, but were limited to about a week in duration due to the non-hermetic sealing of the pumps. Application of robust computational simulation and bench top testing have produced a unique new kind of VAD, offering the flow capacity and reliability of rotary pumps, but adding physiologically relevant pulsatility without excessive shear rates. Future efforts will implement full hermeticity to extend animal study durations and confirm von Willebrand Factor compatibility.

Utilisation of Ambient Laser Desorption Ionisation Mass Spectrometry (ALDI-MS) Improves Lipid-Based Microbial Species Level Identification

The accurate and timely identification of the causative organism of infection is important in ensuring the optimum treatment regimen is prescribed for a patient. Rapid evaporative ionisation mass spectrometry (REIMS), using electrical diathermy for the thermal disruption of a sample, has been shown to provide fast and accurate identification of microorganisms directly from culture. However, this method requires contact to be made between the REIMS probe and microbial biomass; resulting in the necessity to clean or replace the probes between analyses. Here, optimisation and utilisation of ambient laser desorption ionisation (ALDI) for improved speciation accuracy and analytical throughput is shown. Optimisation was completed on 15 isolates of Escherichia coli, showing 5 W in pulsatile mode produced the highest signal-to-noise ratio. These parameters were used in the analysis of 150 clinical isolates from ten microbial species, resulting in a speciation accuracy of 99.4% - higher than all previously reported REIMS modalities. Comparison of spectral data showed high levels of similarity between previously published electrical diathermy REIMS data. ALDI does not require contact to be made with the sample during analysis, meaning analytical throughput can be substantially improved, and further, increases the range of sample types which can be analysed in potential direct-from-sample pathogen detection.

Evaluation of Two Femoral Arterial Cannulae With Conventional Non-Pulsatile and Alternative Pulsatile Flow in a Simulated Adult ECLS Circuit.

The objective of this study is to evaluate the hemodynamic characteristics of two femoral arterial cannulae in terms of circuit pressure, pressure drop, and hemodynamic energy transmission under non-pulsatile and pulsatile modes in a simulated adult extracorporeal life support (ECLS) system. The ECLS circuit consisted of i-cor diagonal pump and console (Xenios AG, Heilbronn, Germany), an iLA membrane ventilator (Xenios AG), an 18 Fr or 16 Fr femoral arterial cannula (Xenios AG), and a 23/25 Fr Estech remote access perfusion (RAP) femoral venous cannula (San Ramon, CA, USA). The circuit was primed with lactated Ringer's solution and packed red blood cells to achieve a hematocrit of 35%. All trials were conducted at room temperature with flow rates of 1-4 L/min (1 L/min increments). The pulsatile flow settings were set at pulsatile frequency of 75 bpm and pulsatile amplitudes of 1000-4000 rpm (1000 rpm increments). Flow and pressure data were collected using a custom data acquisition system. Total hemodynamic energy (THE) is calculated by multiplying the ratio between the area under the hemodynamic power curve (∫flow×pressure dt) and the area under the pump flow curve (∫flow dt) by 1332. The pressure drop across the arterial cannula increased with increasing flow rate and decreasing cannula size. The pressure drops of 18 Fr and 16 Fr cannulae were 19.4-24.5 and 38.4-45.3 mmHg at 1 L/min, 55.2-56.8 and 110.9-118.3 mmHg at 2 L/min, 94.1-105.1 and 209.7-215.1 mmHg at 3 L/min, and 169.2-172.6 and 376.4 mmHg at 4 L/min, respectively. Pulsatile flow created more hemodynamic energy than non-pulsatile flow, especially at lower flow rates. The percentages of THE loss across 18 Fr and 16 Fr cannula were 16.0-18.7 and 27.5-30.8% at 1 L/min, 35.1-35.7 and 52.3-53.8% at 2 L/min, 48.3-50.3 and 67.3-68.4% at 3 L/min and 62.9-63.1 and 79.0% at 4 L/min. The hemodynamic performance of the arterial cannula should be evaluated before use in clinical practice. The pressure drops and percentages of THE loss across two cannulae tested using human blood were higher compared to the manufacturer's data tested using water. The cannula size should be chosen to match the expected flow rate. In addition, this novel i-cor ECLS system can provide non-pulsatile and ECG-synchronized pulsatile flow without significantly increasing the cannula pressure drop and hemodynamic energy loss.