In vivo evaluation of the pulsatile ECLS sysem

 Extracorporeal life support (ECLS) systems have been increasingly applied to groups of patients with cardiorespiratory failure, including pediatric and adult patients with respiratory failure. Current pulsatile ECLS systems use a single pulsatile blood pump that generates a high inlet pressure in the membrane oxygenator. To minimize this high inlet pressure, we have developed a new and improved ECLS system, twin pulse life support (T-PLS). To analyze the advantages of T-PLS, we have compared T-PLS with a single pulsatile ECLS system. An acute heart failure model was constructed by using a pulmonary artery banding technique. Fourteen pigs (22–31 kg) were used, with cardiac outputs of 2.0 l/min and a V/Q ratio set at 1. Cannulae of 28 Fr and 18 Fr were used in the right atrium and aorta, respectively. A polypropylene hollow-fiber membrane oxygenator and four polymer valves 30 mm in diameter were used in the T-PLS system. In the single pulsatile ECLS system, Medtronic Hall monostrut valves were used. To evaluate blood cell trauma in both pulsatile ECLS systems, plasma free hemoglobin (fHb) was measured while the systems were in use. The results show that fHb levels in T-PLS are lower than fHb levels in the single pulsatile ECLS system. There is a possibility that T-PLS could be used as an ECLS system for emergency situations. Received: June 7, 2002 / Accepted: December 10, 2002 Present address: Department of Artificial Organs, Research Institute, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita 565-8565, Japan Tel. +81-6-6833-5012; Fax +81-6-6835-5406 e-mail: hslee@ri.ncvc.go.jp Correspondence to:H.S. Lee     

In vivo evaluation of the pulsatile ECLS system.

Extracorporeal life support (ECLS) systems have been increasingly applied to groups of patients with cardiorespiratory failure, including pediatric and adult patients with respiratory failure. Current pulsatile ECLS systems use a single pulsatile blood pump that generates a high inlet pressure in the membrane oxygenator. To minimize this high inlet pressure, we have developed a new and improved ECLS system, twin pulse life support (T-PLS). To analyze the advantages of T-PLS, we have compared T-PLS with a single pulsatile ECLS system. An acute heart failure model was constructed by using a pulmonary artery banding technique. Fourteen pigs (22-31 kg) were used, with cardiac outputs of 2.0 l/min and a V/Q ratio set at 1. Cannulae of 28 Fr and 18 Fr were used in the right atrium and aorta, respectively. A polypropylene hollow-fiber membrane oxygenator and four polymer valves 30 mm in diameter were used in the T-PLS system. In the single pulsatile ECLS system, Medtronic Hall monostrut valves were used. To evaluate blood cell trauma in both pulsatile ECLS systems, plasma free hemoglobin (fHb) was measured while the systems were in use. The results show that fHb levels in T-PLS are lower than fHb levels in the single pulsatile ECLS system. There is a possibility that T-PLS could be used as an ECLS system for emergency situations.     

Cross flow ultrafiltration studies on solutions of pectin with pulsatile flow in-situ cleaning

A study was conducted to evaluate the cross flow tubular ultrafiltration behavior of aqueous solutions of pectin. The effectiveness of pulsatile flow as a cleaning-in-place (CIP) technique to improve permeate flux was undertaken on the above mentioned solution. This investigation is part of a study to apply membrane filtration in the clarification of tropical fruit juice. The main variables, which were investigated, include the concentration of pectin, pulse frequency and amplitude. It was found that the amount of pectin in the solution significantly affects its ultrafiltration behavior. From the observed profiles, it is evident that the formation of gel layer on the membrane surface is responsible for the leveling of flux at high pressures. The presence of pectin was found to affect the properties of the solution such as viscosity, pH and the size of pectin colloid. Improvements in the permeate flux for pectin solution were obtained by employing pulsatile flow cleaning-in-place technique. Both pulse frequency and amplitude are important parameters that can improve the improvement of in-situ cleaning method. Similar to several findings reported in the literature, pulsatile flow showed significant effectiveness of about 60% higher flux when the ultrafiltration process is operated under laminar condition.     

In vitro evaluation of the performance of Korean pulsatile ECLS (T-PLS) using precise quantification of pressure-flow waveforms

The Twin-Pulse Life Support System (T-PLS) is a novel pulsatile extracorporeal life support system developed in Korea. It has been reported that the T-PLS achieves higher levels of tissue perfusion of the kidney during short-term extracorporeal circulation and provides more blood flow to coronary artery than nonpulsatile blood pumps. However, these results lack pulsatility quantifications and thus make it hard to analyze the effects of pulsatility upon hemodynamic performance. We have adopted the concepts of hemodynamic energy, energy equivalent pressure (EEP), and surplus hemodynamic energy (SHE) to evaluate pulsatility performance in the different circuit configurations of the T-PLS and a membrane oxygenator (MO) in vitro. In a mock system, three different circuits were constructed depending on the location of an MO: pump-MO-pump (serial), MO-pumps (parallel A), and pumps-MO (parallel B). In parallel A, a low-resistance MO was used to preserve the pulsatility from the pump. All circuits showed good pulsatility in terms of EEP (serial: 13.2% +/- 3.2%, parallel A: 10.0% +/- 1.6%, parallel B: 7.00% +/- 1.1%; change from aortic pressure to EEP; p < 0.003). The SHE levels were 17,404 +/- 3750 ergs/cm3, 13,170 +/- 1486 ergs/cm3, and 9192 +/- 1122 ergs/cm3 in each circuit setup (p < 0.001). Although EEP levels were somewhat lower, both parallel types provided higher pump output compared with the serial type (serial: 1.87 +/- 0.29 l/min, parallel A: 3.09 +/- 0.74 l/min, parallel B: 3.06 +/- 0.56 l/min; p < 0.003 except parallel A vs. parallel B, p = 0.90). Conclusively, the precise quantifications of pressure flow waveforms, EEP, and SHE are valuable tools for evaluating pulsatility of the mechanical circulatory devices, and are expected to be used as additional performance indexes of a blood pump. The pulsatility performances are different according to circuit setups. However, the parallel A circuit could achieve higher pump output and generate adequate pulsatility level. Thus, the parallel A circuit is suggested as the optimal configuration in T-PLS applications.     

Pulsatile flow and atherogenesis: results from in vivo studies.

Compliance mismatch between prosthetic vascular replacement (possibly stented) and native artery is considered to be an important factor in implant failure due, e.g., to vascular remodeling, tissutal growth or intimal hyperplasia (IH). From an in vivo study involving altered vascular mechanics (and, consequently, compliance mismatch), carried out using the Moncada model of atherosclerosis development and smooth muscle cell (SMC) proliferation, the hemodynamic assessment was followed by means of real-time multigated ultrasound profilometry, of collared carotid artery using two different models: non-constrictive and constrictive plastic collars, wrapped around the vessel. The experiments provided the real-time measurement of velocity profiles in vivo and the subsequent estimation of wall shear stresses, locally responsible for the altered hemodynamics. Endothelium modifications were correlated with local hemodynamic alterations by using statistical regression analysis of the development of intimal hyperplasia and the mechanical stimulus applied to the endothelium by means of the two different manipulation models. Different correlations were found between wall shear rate and IH in the two models, showing the importance of the vascular pulsatility in determining SMC proliferation. This result could be useful in minimizing the negative consequences of clinical interventions such as graft and/or stent implantation.     

The dynamics of pulsatile flow in the coronary arteries

Summary The coronary arteries are a system of elastic tubes with one end open to the aorta and with a high resistance at the other end.The basic pattern of coronary input flow is determined 1. by the primary inflow wave due to the aortic pressure pulsation and 2. by a secondary wave which is generated by the periodic obstruction of outflow at the peripheral resistance due to the contraction of the heart.By means of the simplified model of a homogeneous elastic tube, details and oscillations of the coronary flow pattern could be explained as due to reflection and superposition of these primary and secondary waves. Flowpatterns constructed by use of this model were compared with flow pulses recorded in anesthetized dogs in the left circumflex coronary artery with an electromagnetic flowmeter.A characteristic feature of the apparent input impedance of a coronary artery has been found experimentally and could be explained by the fact, that the myocardial contraction serves as an additional energy source within the coronary system.The possible usefulness and physiological importance of the application of analytical methods to the hemodynamics of the coronary arteries is discussed.Supported by NIH Grant HE-09694 and the Graduate Incentive Fund from the State of Virginia.     

Large-Eddy simulation of pulsatile blood flow

Large-Eddy simulation (LES) is performed to study pulsatile blood flow through a 3D model of arterial stenosis. The model is chosen as a simple channel with a biological type stenosis formed on the top wall. A sinusoidal non-additive type pulsation is assumed at the inlet of the model to generate time dependent oscillating flow in the channel and the Reynolds number of 1200, based on the channel height and the bulk velocity, is chosen in the simulations. We investigate in detail the transition-to-turbulent phenomena of the non-additive pulsatile blood flow downstream of the stenosis. Results show that the high level of flow recirculation associated with complex patterns of transient blood flow have a significant contribution to the generation of the turbulent fluctuations found in the post-stenosis region. The importance of using LES in modelling pulsatile blood flow is also assessed in the paper through the prediction of its sub-grid scale contributions. In addition, some important results of the flow physics are achieved from the simulations, these are presented in the paper in terms of blood flow velocity, pressure distribution, vortices, shear stress, turbulent fluctuations and energy spectra, along with their importance to the relevant medical pathophysiology.     

Simulation of pulsatile flow in arteries: a utilitarian approach.

A general purpose subroutine package was designed for research and teaching applications to perform a one-dimensional analysis of arterial hemodynamics. A mathematical model of a nonuniform elastic tube was developed and programmed for computer solution. New features of the model include various proximal and distal boundary conditions and arbitrarily definable lumped and distributed sideflows. The model allows simulation of a wide variety of experiments and the comparison of waveforms measured in arterial segments with the computed waveforms. The software permits convenient variation of numerous model parameters including the stiffness of the arterial wall, the geometric taper and the elastic taper. It may permit an interactive simulation controlled from a graphical terminal.     

The effects of pulsatile flow upon renal tissue perfusion during cardiopulmonary bypass: a comparative study of pulsatile and nonpulsatile flow

This study was conducted to directly compare the effects of pulsatile and nonpulsatile blood flow in the extracorporeal circulation upon renal tissue perfusion by using a tissue perfusion measurement system. A total cardiopulmonary bypass circuit was constructed to accommodate twelve Yorkshire swine, weighing 20 approximately 30 kg. Animals were randomly assigned to group 1 (n = 6, nonpulsatile centrifugal pump) or group 2 (n = 6, pulsatile T-PLS pump). A tissue perfusion measurement probe (Q-Flow 500) was inserted into the renal parenchymal tissue, and the extracorporeal circulation was maintained for an hour at a pump flow rate of 2 L/min after aortic cross-clamping. Tissue perfusion flow in the kidney was measured before bypass and every 10 minutes after bypass. Renal tissue perfusion flow was substantially higher in the pulsatile group throughout bypass (ranging 48.5-64.1 ml/min/100 g in group 1 vs. 51.0-88.1 ml/min/100 g in group 2). The intergroup difference was significant at 30 minutes (47.5 +/- 18.3 ml/min/100 g in group 1 vs. 83.4 +/- 28.5 ml/min/100 g in group 2; p = 0.026). Pulsatile flow achieves higher levels of tissue perfusion of the kidney during short-term extracorporeal circulation. A further study is required to observe the effects of pulsatile flow upon other vital organs and its long-term significance.     

Optimization of the circuit configuration of a pulsatile ECLs: an in vivo experimental study

An extracorporeal life support system (ECLS) with a conventional membrane oxygenator requires a driving force for the blood to pass through hollow fiber membranes. We hypothesized that if a gravity-flow hollow fiber membrane oxygenator is installed in the circuit, the twin blood sacs of a pulsatile ECLS (the Twin-Pulse Life Support, T-PLS) can be placed downstream of the membrane oxygenator. This would increase pump output by doubling pulse rate at a given pumpsetting rate while maintaining effective pulsatility. The purpose of this study was to determine the optimal circuit configuration for T-PLS with respect to energy and pump output. Animals were randomly assigned to 2 groups in a total cardiopulmonary bypass model. In the serial group, a conventional membrane oxygenator was located between the twin blood sacs of the T-PLS. In the parallel group, the twin blood sacs were placed downstream of the gravity-flow membrane oxygenator. Energy equivalent pressure (EEP), surplus hemodynamic energy (SHE) and pump output were collected at the different pump-setting rates of 30, 40, and 50 beats per minute (BPM). At a given pump-setting rate the pulse rate doubled in the parallel group. Percent changes of mean arterial pressure to EEP were 13.0 +/- 1.7, 12.0 +/- 1.9, and 7.6 +/- 0.9% in the parallel group, while 22.5 +/- 2.4, 23.2 +/- 1.9, and 21.8 +/- 1.4 in the serial group at 30, 40, and 50 BPM of pump-setting rates. SHE at each pump setting rate was 20,131 +/- 1408, 21,739 +/- 2470, and 15,048 +/- 2108 erg/ cm3 in the parallel group, while 33,968 +/- 3001, 38,232 +/- 3281, 37,964 +/- 2693 erg/cm3 in the serial group. Pump output was higher in the parallel circuit at 40, and 50 BPM pump-setting rates (3.1 +/- 0.2, 3.7 +/- 0.2 L/min vs. 2.2 +/- 0.1 and 2.5 +/- 0.1 L/min, respectively, p =0.01). Either parallel or serial circuit configuration of T-PLS generates effective pulsatility. As for the pump out, the parallel circuit configuration provides higher flow than the serial circuit configuration by doubling the pulse rate at a given pump-setting rate.     

Effect of pulsatile swirling flow on stenosed arterial blood flow

The existence of swirling flow phenomena is frequently observed in arterial vessels, but information on the fluid-dynamic roles of swirling flow is still lacking. In this study, the effects of pulsatile swirling inlet flows with various swirling intensities on the flow field in a stenosis model are experimentally investigated using a particle image velocimetry velocity field measurement technique. A pulsatile pump provides cyclic pulsating inlet flow and spiral inserts with two different helical pitches (10D and 10/3D) induce swirling flow in the stenosed channel. Results show that the pulsatile swirling flow has various beneficial effects by reducing the negative wall shear stress, the oscillatory shear index, and the flow reverse coefficient at the post-stenosis channel. Temporal variations of vorticity fields show that the short propagation length of the jet flow and the early breakout of turbulent flow are initiated as the swirling flow disturbs the symmetric development of the shear layer. In addition, the overall energy dissipation rate of the flow is suppressed by the swirling component of the flow. The results will be helpful for elucidating the hemodynamic characteristics of atherosclerosis and discovering better diagnostic procedures and clinical treatments.     

Retinal electrophysiology for toxicology studies: Applications and limits of ERG in animals and ex vivo recordings

Assessing retinal drug toxicity is becoming increasingly important as different molecules are now developed for the treatment of neurodegenerative diseases and vascular disorders. In pharmacology and toxicology, the electroretinogram (ERG) and the multielectrode array (MEA) recording techniques can be used to quantify the possible side effects of retino-active xenobiotics. Toxicity testing requires the use of rodent as well as non-rodent models for extrapolation to the human model when determining risk and safety. Animal species differ in their retinal anatomo-physiology: most rodents used in toxicology studies are essentially nocturnal species, whereas the non-rodent laboratory species normally used (e.g. dogs, pigs and monkeys) are diurnal. The ratio between the photoreceptor populations which varies from species to species, should be considered when designing the experiment protocol and the interpretation. The described ERG procedures are designed to comply with all applicable good laboratory practice standards. Use of these procedures should yield an acceptable level of intra- and inter-subject variability for compiling a historical database, and for detecting possible retinal toxicity in animal studies. They could therefore be used as specific and standardized tools for screening of potential retinotoxic molecules in drug discovery and development in order to compare methods and results with those obtained in human electrophysiological assessments. Recording of ganglion cell light responses on ex vivo retina with the MEA technique can further demonstrate how retino-active xenobiotics affect retinal visual information processing by eliminating potential obstacles related to bioavailability and blood barrier permeability.     

Turbulence downstream from the Ionescu-Shiley bioprosthesis in steady and pulsatile flow

The turbulence generated downstream from an aortic Ionescu-Shiley bioprosthesis has been investigated in vitro with both steady and pulsatile flow; Instantaneous point velocities were measured using laser-Doppler anemometry (LDA) at numerous preselected locations in the flow. The mean and RMS velocities from these data at each location were then used to estimate the laminar and turbulent shear in the bulk flow as a function of radial position on a cross-section of the flow system downstream from the mounted prosthesis. Estimated total shear stresses were found in the bulk flow that were of sufficient magnitude to possibly cause haemolysis and initiate platelet chemical-release reactions. For steady flow and at peak pulsatile flow, maximum total shear stresses were estimated to be 120 N m⁻² and 100 N m⁻², respectively, over more than 5 per cent of the flow cross-section. The spatial distribution of the elevated shear stresses correlates well with the valve superstructure. It is concluded that these elevated stresses are a direct consequence of the notable flow constriction generated by the valve’s fully opened leaflets. deceased     

Pressure peaking in pulsatile flow through arterial tree structures

An analytical iterative scheme is presented for computing the local characteristics of pressure and flow waves as they progress along a tree structure and become modified by wave reflections. Results are obtained to illustrate the phenoenon of pressure peaking under two different sets of circumstances. In the first case, the propagation of a single harmonic wave along a simple tree is considered, where wave reflections modify the amplitude of the pressure wave as it travels. In the second case, the propagation of a composite wave along a tree with multiple branches is considered, where wave reflections modify the shape of the wave as it travels and cause it to peak. The results demonstrate unambiguously that the root cause of this phenomenon is wave reflections caused by stepwise decreases in admittance, as has been previously suggested, rather than due to nonlinear interactions, as has also been previously suggested. It is shown clearly that even when wave reflections combine linearly, they lead to considerable peaking in the pressure waveform.     

Numerical study of nonlinear pulsatile flow in S-shaped curved arteries

The nonlinear pulsatile blood flow in S-shaped curved arteries was studied with finite element method. Numerical simulations for flows in two models of S-shaped curved arteries with different diameters and under the same boundary conditions were performed. The temporal and spatial distributions of hemodynamic variables during the cardiac cycle such as velocity field, secondary flow, pressure, and wall shear stresses in the arteries were analyzed. Results of numerical simulations showed that the secondary flow in the larger S-shaped curved artery is more complex than that in the smaller one; stronger eddy flow occurred in the inner bends of curved arteries; pressure and wall shear stresses changed violently in the curved arteries, especially in the larger model. These hemodynamic variables in curved arteries will cause important effects on the function of arterial endothelium in the region. For instance, they may lead to the proliferation of smooth muscle cells and the thickening of the intima, and cardiovascular diseases such as atherosclerosis may develop in such regions. Due to having the special blood flow characteristics in the S-shaped arteries, it is worthwhile to study flow in this kind of curved artery. The comprehensive theoretical foundation showed in the present study can be extended to approach problems of nonlinear pulsatile flow in curved arteries with more complex geometrical shape.