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PubMed1988

Influence of cardiac flow rate on turbulent shear stress from a prosthetic heart valve.

Elevated turbulent shear stresses associated with sufficient exposure times are potentially damaging to blood constituents. Since these conditions can be induced by mechanical heart valves, the objectives of this study were to locate the maximum turbulent shear stress in both space and time and to determine how the maximum turbulent shear stress depends on the cardiac flow rate in a pulsatile flow downstream of a tilting disk valve. Two-component, simultaneous, correlated laser velocimeter measurements were recorded at four different axial locations and three different flow rates in a straight tube model of the aorta. All velocity data were ensemble averaged within a 15 ms time window located at approximately peak systolic flow over more than 300 cycles. Shear stresses as high as 992 dynes/cm2 were found 0.92 tube diameters downstream of the monostrut, disk valve. The maximum turbulent shear stress was found to scale with flow rate to the 0.72 power. A repeatable starting vortex was shed from the disk at the beginning of each cycle.

Blood Flow Velocity↗
PubMed1986

[Angiocinedensitometry with ECG-controlled injections in patients with healthy kidneys and kidney tumors].

According to the method, the necessary equipment and actual attainment of measurements, the results of cinedensitometric evaluations are discussed. The results are based on angiographic examinations of 80 patients (41 hypernephroma and 39 normal kidneys) who have been studied using X-ray cinedensitometry. It could be proven that with the ECG-triggered injection of contrast-medium, measurements of the pulsatile flow in the renal artery during the various periods of heart-motions could be performed with a high degree of accuracy. Curves of the velocity of the bloodflow are therefore attainable. The average velocities of bloodflow show normal values of 8.5 ml/s in normal kidneys, which means 570 ml/min. In hypernephromas, there were increased velocities of bloodflow measuring up to 1400 ml/min, that is a maximal flow of 760 ml/min. Depending upon the pulsatile flow the curves of the bloodflow velocity are very distinctive. The examples of values of bloodflow velocity in hypertrophic kidneys or in hypervascularized renal tumors support these findings. The lower the measured flow velocity is, the more uniform the pattern of the flow profile will be.

Absorptiometry, Photon↗
PubMed1996

Effects of geometry and flow division on flow structures in models of the distal end-to-side anastomosis.

Flow structures in models of the distal end-to-side anastomosis were visualised under steady and pulsatile flow conditions using planar illumination of suspended tracer particles. The effects of anastomosis geometry and flow in the proximal artery were investigated in models with anastomosis angles of 15, 30 or 45 degrees. The flow patterns in steady flow were highly three-dimensional and comprised two helical vortices in the distal artery, a recirculation vortex in the occluded proximal arterial segment and a stagnation point on the floor of the artery. Flow separation was observed at the toe of the anastomosis in the 30 and 45 degree models only. A second separation point was also found on the near wall of the 30 degree models at higher flow rates. Downstream flow in the proximal artery reduced and even eliminated the flow recirculation at the heel of the anastomosis, while upstream flow resulted in a captive vortex at the heel and flow reversal at the toe. In pulsatile flow, the secondary flow components in the distal artery became more pronounced during flow deceleration, particularly at higher Reynolds numbers. Significant flow reversal was observed at the toe of the anastomosis and this extended several vessel diameters along the near wall of the artery and upstream into the hood of the graft. The floor of the artery was subjected to a continually varying shear rate caused by the movement of the stagnation point during the pulsatile cycle. The results are in agreement with the observation that intimal hyperplasia occurs in regions of flow separation at the toe and the heel, and flow stagnation on the floor of the anastomosis.

Anastomosis, Surgical↗
PubMed2000

Assessment of arterial stenosis in a flow model with power Doppler angiography: accuracy and observations on blood echogenicity.

The objective of the project was to study the influence of various hemodynamic and rheologic factors on the accuracy of 3-D power Doppler angiography (PDA) for quantifying the percentage of area reduction of a stenotic artery along its longitudinal axis. The study was performed with a 3-D power Doppler ultrasound (US) imaging system and an in vitro mock flow model containing a simulated artery with a stenosis of 80% area reduction. Measurements were performed under steady and pulsatile flow conditions by circulating, at different flow rates, four types of fluid (porcine whole blood, porcine whole blood with a US contrast agent, porcine blood cell suspension and porcine blood cell suspension with a US contrast agent). A total of 120 measurements were performed. Computational simulations of the fluid dynamics in the vicinity of the axisymmetrical stenosis were performed with finite-element modeling (FEM) to locate and identify the PDA signal loss due to the wall filter of the US instrument. The performance of three segmentation algorithms used to delineate the vessel lumen on the PDA images was assessed and compared. It is shown that the type of fluid flowing in the phantom affects the echoicity of PDA images and the accuracy of the segmentation algorithms. The type of flow (steady or pulsatile) and the flow rate can also influence the PDA image accuracy, whereas the use of US contrast agent has no significant effect. For the conditions that would correspond to a US scan of a common femoral artery (whole blood flowing at a mean pulsatile flow rate of 450 mL min(-1)), the errors in the percentages of area reduction were 4.3 +/- 1.2% before the stenosis, -2.0 +/- 1.0% in the stenosis, 11.5 +/- 3.1% in the recirculation zone, and 2.8 +/- 1.7% after the stenosis, respectively. Based on the simulated blood flow patterns obtained with FEM, the lower accuracy in the recirculation zone can be attributed to the effect of the wall filter that removes low flow velocities. In conclusion, the small errors reported in vitro may support the clinical use of this technique.

Algorithms↗
PubMedDate not supplied

Thromboembolization associated with sudden increases in flow in a coronary stent ex vivo shunt model.

To observe the dynamics of thromboembolism (TE) in an animal model, a carotid-carotid arterial ex vivo shunt was developed. A coronary stent deployed in a 3.5 mm polyvinylchloride (PVC) tubing segment was used as a model device in the shunt. A light-scattering microemboli detector monitored the embolic content of the blood flowing through the shunt at 50-150 ml/min as determined by a clamp-on ultrasound flow probe. The stent was found to actively develop thrombi and release emboli for 1-3 hours when the activated clotting time (ACT) was maintained between 125 and 150 seconds. The shunt flow rate fluctuated considerably (from 50 to 150 ml/min) depending on the animal's activity. When the time profile of this fluctuating flow rate was super imposed on the time profile of embolization, it was noted that sudden increases in flow rate were associated with incidents of embolization. Statistically, sudden flow rate increases of 100% or more were accompanied by embolic events 95% of the time (p < 0.01). Based on the results of this study, it was postulated that the increased embolization may be due to the fluid forces associated with accelerating flow. To explore this postulate, in vitro studies were conducted to compare the effects of pulsatile flow with steady flow on stent induced TE. Results of this study suggested a significant increase (100%) in both stent thrombosis and embolism during pulsatile flow compared with steady flow.

Animals↗
PubMed1988

In vitro analysis of performance of porcine xenografts with inward bending of stent posts: real-time measurement of valve orifice area using an area meter.

The influence of inward bending of the stent posts on bioprosthetic valve function was assessed in a hydromechanical simulation of the left heart. A Carpentier-Edwards mitral xenograft (31 mm) and an aortic xenograft (27 mm) were used. Valve function was evaluated before and after the stent posts were bent inward 15 degrees by suture constriction of the tops of the three posts. To evaluate the effects of the stent-post deformity on valve performance, the mean transvalvular pressure drop during steady flow, the bioprosthetic valve orifice area, and the maximum valve opening and closing speeds during pulsatile flow were measured using an area meter. Steady-flow data showed identical transvalvular pressure drops, and no significant difference in valve performance was detected in the pulsatile-flow study under the two experimental conditions (i.e., normal valve and deformed valve). We conclude that a 15-degree inward bending of the stent posts does not appreciably affect valve function in vitro.

Aortic Valve↗
PubMed1994

Unsteady entrance flow development in a straight tube.

The entrance conditions for pulsatile flow are important in the understanding blood flow out of the heart and in developing regions at branches. The pulsatile entrance flow was solved using a spectral element simulation of the full unsteady Navier-Stokes equations. A mean Reynolds number of 200 and a range of Womersley parameters from 1.8 to 12.5 was used for a sinusoidal inlet flow waveform 1 + sin (omega t). Variations in the entrance length were observed during the pulsatile cycle. The amplitude of the entrance length variation decreased with an increase in the Womersley parameter. The phase lag between the entrance length and the inlet flow waveform increased for Womersley parameter alpha up to 5.0 and decreased for alpha larger than 5.0. For low alpha, the maximum entrance length during pulsatile flow was approximately the same as the steady entrance length for the peak flow. For high varies; is directly proportional to, the pulsatile entrance length was more uniform during the cycle and tended to the entrance length for the mean flow. The wall shear rate reached its far downstream value after only about half of the entrance length and also exhibited a dependence on alpha. The results quantify the entrance conditions typically encountered in studies of the arterial system.

Evaluation Studies as Topic↗
PubMed1999

Effect of pulse pressure on vascular smooth muscle cell migration: the role of urokinase and matrix metalloproteinase.

Plasminogen activator (PA) expression plays an important role in smooth muscle cell (SMC) migration and may therefore contribute to mechanical force-induced arterialization of vein grafts. The aim of this study was to determine whether pulse pressure due to pulsatile flow modulates SMC migration via urokinase (u-PA)-dependent mechanisms. Using a perfused transcapillary culture system, human umbilical vein SMC were exposed to pulse pressures (0-56 mmHg), in the absence or presence of human umbilical vein endothelial cells (EC) by varying pulsatile flow rates (0 ml/min to 25 ml/min). SMC cultured in the absence of EC increased their migration following exposure to increased pulse pressure (248+/-14%). Both u-PA and matrix metallo-proteinase 1 (MMP-1) expression was significantly elevated in SMC exposed to pressure as compared to static controls. The role of proteases in the pulse pressure-induced enhancement of SMC migration was confirmed following pretreatment with aprotinin, an anti u-PA antibody and metalloproteinase inhibitors (181+/-14% for aprotinin vs. 256+/-25% for control, 108+/-4% for anti-u-PA antibody vs. 233+/-17% for non-immune IgG, and 114+/-9% for BB-94, 105+/-7% for BB-3103 vs. 222+/-5% for control). Using SMC derived from u-PA gene knock-out mice, the SMC migratory response to increased pulse pressure was completely inhibited despite a significant increase in MMP expression in these cells. These results suggest that pulse pressure due to pulsatile flow induces SMC migration in vitro via u-PA and MMP-dependent mechanisms. Moreover, u-PA gene deletion results in blunting of pressure-induced SMC migration despite the endogenous upregulation of metalloproteinase. Modulation of u-PA expression by pressure may thus represent an important mechanism whereby hemodynamic forces regulate smooth muscle cell migration.

Animals↗
PubMed1996

Hydrodynamic function of tilting disc prostheses and bileaflet valves in double valve replacement.

OBJECTIVE: To determine the energy loss attributable to prosthetic valve size and design in double valve replacement, energy consumption of mitral valves (size #25 to #29), of two different designs (Bjork Shiley tilting disc and Carbomedics bileaflet valves), in combination with a small (#21) and large sized (#27) aortic prosthesis, were analyzed in a flow simulator. METHODS: A pulsatile flow simulator was used to reproduce physiological ventricular dynamics and to match the input and output impedances of the human left ventricle. Hydrodynamic performance was determined as stroke work, closing work and leak work for each combination of valves at low flow (5 liters per minute) and high flow (9 liters per minute) conditions. RESULTS: At low flow no decrease of energy requirement was found with the use of a mitral valve larger than #25. At high flow the #27 and #29 mitral valves required less energy compared to a #25 mitral valve, in combination with a large aortic prosthesis. The #29 mitral prosthesis revealed similar results as the #27. With the use of a large aortic prosthesis a remarkable reduction of total flow work was shown. These results were found in both designs. In comparison of the two designs, tilting disc valves required more energy for stroke and closure of the valve, although less energy for leakage. In total, energy requirements were higher for tilting disc valves. COMMENTS: A hydrodynamic advantage for the use of a mitral valve larger than #25 was found only with the combination of a large aortic prosthesis and high flow. Hydrodynamic data favor the use of bileaflet prosthesis especially for a patient who is expected to exercise.

Aortic Valve↗
PubMed1996

Comparison of passive and active perfusion catheters: an in vitro study in a pulsatile coronary flow model.

Perfusion balloon catheters are designed to provide continuous transcatheter blood flow and thereby reduce myocardial ischemia during coronary angioplasty. To compare the transcatheter flow rates of active and passive (auto-) perfusion catheters, a well-controlled experimental study was performed in a circulation model that duplicates the phasic, predominantly diastolic flow pattern of the left coronary artery. Mean diastolic coronary driving pressure varied between 20 and 100 mm Hg. For the autoperfusion catheters, a strong relationship between transcatheter flow and diastolic coronary driving pressure was found. For example, a coronary driving pressure of 80 mm Hg provided a coronary flow of 30 ml/min (RX-Perfusion [RP], ACS), 28 ml/min (Speedflow [SF], Schneider), 20 ml/min (Lifestream [LS], ACS), and 19 ml/min (Flowtrack [FT], ACS). Reduction of driving pressure to 40 mm Hg decreased the absolute transcatheter flow, which was now 16 ml/min (RP), 13 ml/min (SF), and 10 ml/min (LS and FT). The relative catheter flow (the ratio of absolute flow to baseline coronary flow rate without a catheter in place), was independent of actual coronary driving pressure and ranged between 21% +/- 1% (RP) and 14% +/- 1% (FT and LS). For the active perfusion system (Coreflo, Leocor, a maximal transcatheter flow of 82 ml/min was found. Using this active perfusion system, the relative catheter flow increased with decreasing coronary driving pressure:80 --> 40 mm Hg: 56% --> 107%. For all catheters, the distal perfusion decreased between 30% (3.0 mm RP) and 50% (3.0 mm LS) by a 0.014-inch guidewire placed through the inner channel of the catheter. Because of the strong relationship between coronary driving pressure and transcatheter flow, the residual flow through all autoperfusion catheters becomes critical (<20 ml/min), when the coronary driving pressure drops below 50 mm Hg. By contrast, active perfusion systems are independent of the actual coronary driving pressure and are therefore advantageous for prolonged dilation in patients with low aortic pressure.

Angioplasty, Balloon, Coronary↗
PubMedDate not supplied

New investigations of a pulsatile impeller blood pump.

For circulatory assist devices and total artificial heart systems, impeller blood pumps with small total volumes would be fully implantable. One of the main obstacles, however, is generation of a pulsatile flow. The simplest way to overcome this problem is by changing the pump's revolutions per minute (rpm) periodically, but this often results in severe hemolysis. After theoretic analysis, two in vitro models of impeller blood pumps have been devised, producing pulsatile flow with constant rpm. In the first model, the impeller oscillates in an axial direction during constant rotation. The pump is driven by a DC motor (rotating) and a pneumatic device (oscillating). The form of the pulsatile pressure wave depends upon duration and amplitude of the oscillation. With 40% systolic duration and a 50 mm axial amplitude, a 70 mmHg pressure amplitude (170/100) is achieved with a semiphysiologic shape at a flow of 12 L/min. The second model produces a pulsatile flow by differing the gaps between impeller and cap on the inlet pipe. Both the cap and impeller have cone-shaped heads, and impeller oscillations of 1.5-2 mm, for example, results in a pressure pulse of 40 mmHg (150-110) at 7 L/min flow. Results of theoretic analyses have shown that both models create less turbulence in the impeller, with a consequent reduction in blood cell damage as compared to pumps with changing rpms.

Equipment Design↗
PubMed1994

Vascular impedance analysis in dog lung with detailed morphometric and elasticity data.

On the basis of experimentally measured morphometric and elasticity data and model-derived mean pressure-flow conditions, we attempt a theoretical modeling of pulsatile flow in the whole lung. In the model we use the "elastic tube" for arteries and veins, and the vascular impedance in arteries and veins follows Womersley's theory and electric analogue. We employ the "sheet-flow" theory to describe the flow in the capillaries and to obtain the microvascular impedance matrix. The characteristic impedance of each order along the vascular tree, the input impedance at the capillary entrance and exit, and the pulmonary arterial input impedance at the main pulmonary artery are computed under certain physiological conditions. Using the pulsatile flow model, we investigate the effects of arterial vascular obstruction on pulmonary vascular impedance. The model-derived data are compared with the available experimental results in the literature.

Animals↗
PubMed1996

Velocity measurements and flow patterns within the hinge region of a Medtronic Parallel bileaflet mechanical valve with clear housing.

BACKGROUND AND AIMS OF THE STUDY: During recent clinical trials the Medtronic Parallel bileaflet mechanical heart valve was found to have an unacceptable number of valves with thrombus formation when implanted in the mitral position. Thrombi were observed in the hinge region and also in the upstream portion of the valve housing in the vicinity of the hinge. It was hypothesized that the flow conditions inside the hinge may have contributed to the thrombus formation. METHODS: In order to investigate the flow structures within the hinge, laser Doppler anemometry (LDA) measurements were conducted in both steady and pulsatile flow at approximately 70 predetermined sites within the hinge region of a 27 mm Medtronic Parallel mitral valve with transparent housing. The pulsatile flow velocity measurements were animated in time using a graphical software package to visualize the hinge flow field throughout the cardiac cycle. RESULTS: The LDA measurements revealed that mean forward flow velocities through the hinge region were on the order of 0.10-0.20 m/s. In the inflow channel, a large vortical structure was present during diastole. Upon valve closure, peak reverse velocity reached 3 m/s close to the housing wall in the inflow channel. This area also experienced high turbulent shear stresses (> 6000 dynes/cm2) during the leakage flow phase. A disturbed, vortical flow was again present in the inflow channel after valve closure, while slightly above the leaflet peg and relief the flow was essentially stagnant. The high turbulent stresses near the top of the inflow channel, combined with a persistent vortex, implicate the inflow channel of the hinge as a likely region of thrombus formation. CONCLUSIONS: This experimental investigation revealed zones of flow stagnation in the inflow region of the hinge throughout the cardiac cycle and elevated turbulent shear stress levels in the inflow region during the leakage flow phase. These fluid mechanic phenomena are most likely a direct result of the complex geometry of the hinge of this valve. Although the LDA measurements were conducted at only a limited number of sites within the hinge, these results suggest that the hinge design can significantly affect the washout capacity and thrombogenic potential of the Medtronic Parallel bileaflet mechanical heart valve. The use of LDA within the confines of the hinge region of a mechanical heart valve is a new application, made possible by recent advances in manufacturing technologies and a proprietary process developed by Medtronic that allowed the production of a transparent valve housing. Together, these modalities represent a new method by which future valve designs can be assessed before clinical trials are initiated.

Evaluation Studies as Topic↗
PubMed2003

Hemodilution during off-pump coronary artery bypass grafting: can we improve flow and reduce hypercoagulability?

BACKGROUND: The aim of this study was to compare intraoperative coronary graft flows performed on pump and off pump and to evaluate the effects of hemodilution on coronary graft flows in off-pump coronary artery bypass grafting (CABG) patients by using transit time flow measurements (TTFM). METHODS: Three hundred patients undergoing only CABG procedures were enrolled in a prospective randomized manner into 3 groups. Group 1 consisted of 100 patients undergoing operations with standard cardiopulmonary bypass techniques. Group 2 consisted of 100 patients scheduled for revascularizations using off-pump techniques. Group 3 consisted of 100 patients who underwent operations with offpump techniques under controlled hemodilution (hematocrit levels kept between 25% and 28%). TTFM were performed with the coronary Flometer system. Mean flows, pulsatility indices, and flow patterns were evaluated. Twenty-five patients in each group were randomly assigned for control angiography 6 days postoperatively. Thromboelastographic (TEG) measurements were performed for each patient before and after surgery to evaluate the patient's coagulation status. RESULTS: The mean number of anastomoses was higher in group 1 than in groups 2 and 3 (P < .05). Mean arterial pressures and heart rates were similar between groups during measurements. Hematocrit values were higher in group 2 than in groups 1 and 3 (P < .05). Mean flows for left anterior descending coronary artery and right coronary artery territories were significantly lower in group 2 patients (P < .05). For the circumflex artery territory, mean flows did not reach statistically significant levels despite lower flows again in group 2. The pulsatility indices were similar in all 3 groups for all 3 coronary territories. Postoperative coronary angiographic results revealed similar graft patencies among the 3 groups (not significantly different). Postoperative TEG patterns failed to show a hypercoagulable state in off-pump patients. CONCLUSION: Off-pump CABG patients with hemodilution had significantly higher graft flows than off-pump CABG patients without hemodilution. Although we failed to show the existence of a hypercoagulable state for patients in the offpump group, an examination of the TTFM findings suggests that hemodilution may help to improve graft patency in offpump CABG patients during the early postoperative period.

Blood Coagulation Disorders↗
PubMed2001

Pulsatile blood flow effects on temperature distribution and heat transfer in rigid vessels.

The effect of blood velocity pulsations on bioheat transfer is studied. A simple model of a straight rigid blood vessel with unsteady periodic flow is considered. A numerical solution that considers the fully coupled Navier-Stokes and energy equations is used for the simulations. The influence of the pulsation rate on the temperature distribution and energy transport is studied for four typical vessel sizes: aorta, large arteries, terminal arterial branches, and arterioles. The results show that: the pulsating axial velocity produces a pulsating temperature distribution; reversal of flow occurs in the aorta and in large vessels, which produces significant time variation in the temperature profile. Change of the pulsation rate yields a change of the energy transport between the vessel wall and fluid for the large vessels. For the thermally important terminal arteries (0.04-1 mm), velocity pulsations have a small influence on temperature distribution and on the energy transport out of the vessels (8 percent for the Womersley number corresponding to a normal heart rate). Given that there is a small difference between the time-averaged unsteady heat flux due to a pulsating blood velocity and an assumed nonpulsating blood velocity, it is reasonable to assume a nonpulsating blood velocity for the purposes of estimating bioheat transfer.

Biomechanical Phenomena↗
PubMed1996

An in vitro investigation of the retrograde flow fields of two bileaflet mechanical heart valves.

BACKGROUND AND AIM OF THE STUDY: Fluid stresses occurring in retrograde flow fields during valve closure may play a significant role in thrombogenesis. The squeeze flow and regurgitant jets can cause damage to formed blood elements due to high levels of turbulent shear stress. The aim of this study was to characterize in detail the spatial structure and temporal behavior of the retrograde flow fields of the St. Jude Medical and Medtronic Parallel bileaflet mechanical heart valves. METHODS: Three-component, coincident laser Doppler anemometry (LDA) velocity measurements were obtained facilitating the determination of the full Reynolds stress tensor and the principal stresses in the valve flow fields. The experiments were performed in the Georgia Tech aortic flow chamber under physiologic pulsatile flow conditions. Data were collected over several hundred cardiac cycles for subsequent phase window averaging and generation of mean velocity and turbulence statistics over 20 ms intervals. A region approximately 8 mm x 10 mm was mapped 1.0 mm upstream of one hinge of each valve with an incremental resolution of 0.13-0.25 mm. Animation of the data allowed the visualization of the flow fields and a quantitative display of mean velocity and turbulent stress values. RESULTS: In the St. Jude Medical squeeze flow, the peak turbulent shear stress was 800 dynes/cm2 and the peak reverse velocity was 0.60 m/s. In the Medtronic Parallel squeeze flow, the peak turbulent shear stress was 1,000 dynes/cm2 and the peak velocity 0.70 m/s. The leakage jet fields of the two valves were very different: in the case of the St. Jude Medical valve, turbulent shear stresses reached 1,800 dynes/cm2 and peak jet velocity was 0.80 m/s; in the case of the Medtronic Parallel valve, turbulent shear stresses reached 3,690 dynes/cm2 and the peak jet velocity was 1.9 m/s. CONCLUSIONS: The retrograde flow fields of these two bileaflet mechanical heart valves appear to be design-dependent. The elevated turbulent shear stresses generated by both valve designs may indicate a propensity for blood element damage during the reverse flow phase of the cardiac cycle, but the extent of flow disturbance was twice as high with the Medtronic Parallel than with the St. Jude Medical valve. This research should yield a better understanding of the significance of retrograde flow to the functionality and potential thrombogenicity of bileaflet mechanical heart valves and aid in the development of new designs.

Heart Valve Prosthesis↗
PubMed2006

Tissue engineering of autologous human heart valves using cryopreserved vascular umbilical cord cells.

BACKGROUND: Tissue engineering of autologous heart valves with the potential to grow and to remodel represents a promising concept in pediatric cardiovascular surgery. Currently we are exploring the impact of cryopreserved human umbilical cord cells (CHUCCs) for the fabrication of tissue-engineered heart valves for patients diagnosed prenatally with congenital heart lesions, potentially enabling heart valve replacement in the early years of life. METHODS: Human umbilical cord cells were isolated from vascular segments of umbilical cords and cryopreserved in a cell bank. After 12 weeks the cryopreserved cells were again expanded in culture and characterized by histology, immunohistochemistry, and proliferation assays. Trileaflet heart valve scaffolds were fabricated from a porous polymer (P4HB, Tepha Inc, Cambridge, MA) and sequentially seeded with CHUCCs (n = 10). Five of the heart valve constructs were grown for 7 days in a pulse duplicator and, as a control, five constructs were grown under static cell culture conditions for 7 days. Analysis of all tissue-engineered heart valves included histology, immunohistochemistry, electron microscopy, functional analysis, and biomechanical and biochemical examination. RESULTS: We found that CHUCCs remained viable after 12 weeks of cryopreservation and showed a myofibroblast-like morphology that stained positive for alpha-actin and fibroblast specific marker. Histology of the tissue-engineered heart valves showed layered tissue formation, including connective tissue between the inside and the outside of the porous scaffold. Immunohistochemistry was positive for collagen (types I, III, and IV), desmin, laminin, and alpha-actin. Electron microscopy showed that the cells had grown into the pores and formed a confluent tissue layer during maturation in the pulsatile flow system. Biochemical examination showed an increase of extracellular matrix formation in constructs after pulsatile flow exposure compared with the static control group. Functional analysis demonstrated a physiological increase of the intracellular Ca2+ concentration of the recultivated cells and the conditioned constructs after stimulation with histamine. CONCLUSIONS: This study demonstrates in vitro generation of viable and functional human heart valves based on CHUCCs and biomimetic flow culture systems. The CHUCCs demonstrated excellent growth potential and abilities of in vitro tissue formation. These findings suggest the potential benefit of establishing autologous human cell banks for pediatric patients diagnosed intrauterinely with congenital defects that will potentially require heart valve replacement in the early years of life.

Actins↗
PubMed1994

Do we really need pulse? Chronic nonpulsatile and pulsatile blood flow: from the exercise response viewpoints.

The response of the body and the blood pump was evaluated in animals with a pulsatile artificial heart (total artificial heart [TAH]) and those with a nonpulsatile artificial heart (nonpulsatile biventricular bypass [NPBVB]) subjected to the same exercise load. The animals used in this study were 5 calves implanted with a pusher-plate type TAH (45-206 days) and 5 calves implanted with a nonpulsatile centrifugal pump (34-99 days). The pre-exercise pump flow rate was 92.1 +/- 8.1 ml/kg/min for the TAH group and 94.8 +/- 9.1 ml/kg/min for the NPBVB group, with no significant difference between the two groups. The workload was administered at a rate of 1.5 mph for 15 min. The artificial heart driving conditions were kept constant throughout the test period. Sequential changes in hemodynamic response and metabolism were determined before, during, and for 30 min after exercise. Both TAH and NPBVB calves showed excellent tolerance of the workload (1.5 mph exercise); in NPBVB calves, oxygen demand was compensated for by an increase in the arteriovenous oxygen difference during exercise; and norepinephrine showed a greater response in the NPBVB group. Based on the results presented, the nonpulsatile pump seems to lend itself to a mechanically driven artificial heart of the complete implantation type because of its small size, high efficiency, and the lack of need for a compliance chamber.

Animals↗