Artificial organs of the future.
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Artificial Organs↗
Biomedical subjects
D B Olsen
Publications and source records attributed to D B Olsen.
Atrial compliance changes in animal total artificial heart recipients.
Right atrial compliance of chronically implanted total artificial heart animals was calculated from the pressure-volume relationships acquired at autopsy and compared with those of a control animal. The chronically implanted animals showed right atrial dilatation and low compliance. Even though atrial dilatation and decreased compliance have an opposite direct effect on atrial pressures, these changes may, in turn, disturb stretch-dependent volume regulatory processes, resulting in high atrial pressure.
Animals↗
Microbially infected thrombus in animals with total artificial hearts.
In a retrospective study of 330 animals with total artificial hearts (TAH), 103 (31%) had microbially infected thrombi (MIT). The incidence of MIT approximated 75% in the animals surviving more than 100 days. The most common pathogen isolated from animals with MIT was Pseudomonas. Most thrombi appeared to have originated from valve junctions and connectors. Methods to prevent MIT should be aimed at eliminating thrombus formation by improved design and materials and controlling the route of bacterial colonization. These findings suggest that bacterial interaction with the thrombus, device-related bacterial colonization, host immunomodulation, and gut barrier function after TAH implantation need further study.
Animals↗
Determination of atrial shunt size needed to balance an electrohydraulic total artificial heart.
An interatrial shunt (IAS) was developed and tested to balance a volumetrically coupled electrohydraulic total artificial heart (EHTAH). The IAS diameter was determined theoretically with the equation: [formula: see text] where D = orifice diameter, delta P = pressure drop across the orifice, rho = fluid density, Q = volume flow through the orifice, and C = empiric constant. The calculated orifice diameter was 2.9-5.3 mm to keep a 3-5 mmHg pressure difference between left and right atria, with 0.42-1.05 L/min of expected flow through the IAS. Three different sizes (3.4, 5.4, and 5.5 mm) of IAS were implanted and tested in four calves. The in vivo left-right pressure difference ranged from 3 to 8 mmHg, with 0.57-1.38 L/min of theoretically calculated flow through the IAS. At autopsy, none of the IAS showed macroscopic thrombus formation.
Animals↗
Development of an automatic control algorithm for the electrohydraulic total artificial heart without transducers.
To achieve a reliable and simple implantable total artificial heart, the number of implanted transducers providing the physiologic information required for automatic control should be minimized. To address this need, a new automatic control algorithm, based on a transducerless electrohydraulic total artificial heart (EHTAH) system, is proposed. The current EHTAH physiologic control algorithm relies on two implanted pressure transducers. Without these transducers, the information required for automatic control must be extracted from the running motor's parameters. These parameters correlated with the differential pressure across the axial flow pump used to actuate the EHTAH. Changes in this differential were chosen as a cue for cardiac output control. This algorithm can be viewed as depending upon systemic vascular resistance determined by subtracting mean right atrial pressure (RAP) from mean aortic pressure (AoP) and dividing the result by total cardiac output (CO). The difference between mean AoP and mean RAP was confirmed to correlate with the differential hydraulic pressure across the energy converter during the left systolic phase. As an interim configuration, a single differential pressure transducer measuring the differential hydraulic pressure across the energy converter was tested on a Donovan mock circulation system. The resultant CO response shows good sensitivity according to changes in both preload and afterload.
Algorithms↗
Comparison of microsphere and intraoperative quantitation of bronchial blood flow.
Although significant variation in bronchial blood flow (BBF) has been reported, precise quantitation is difficult because of the small sized vessels and variable anatomy. Ventricular balance is critical to the function of the total artificial heart (TAH), and variation in BBF can alter this balance in the bovine model. Bronchial blood flow was measured in 12 calves by two methods: six by the radioactive labeled microsphere technique (MBBF), and six intraoperatively (IBBF) during cardiopulmonary bypass (CPB). In the MBBF group, BBF ranged from 1.9 ml/kg to 16.0 ml/kg, whereas IBBF varied from 2.6 ml/kg to 10 ml/kg (NS). Cardiac output (CO) was significantly higher (p less than 0.0005) in the MBBF group. Bronchial blood flow in both groups was highly variable. The higher flow in the MBBF group may be attributed to the arteriovenous shunting of microspheres, whereas lower flow in the IBBF group may be secondary to physiologic changes during CPB. This technique, described to measure IBBF, can estimate large variations in the natural right to left shunt that contributes to imbalance in the TAH.
Animals↗
Patterns of bacterial infection in calves implanted with artificial hearts.
Device-related infection is one of the most serious potential consequences of total artificial heart (TAH) implantation. This complication must be addressed before the full potential benefit of these devices, especially fully implantable devices, can be realized. A review of research reports and clinical data was conducted to ascertain if similarities existed between the patterns of infection reported in human TAH recipients and those seen in the experimental animal models. Infection was reported in approximately 57% of the human TAH recipients and approximately 47% of the implanted animals. Implant periods ranged from 1-620 days for the humans, and 32-287 days for the animals. The spectrum of organisms isolated from both groups were similar, with a high proportion of infections caused by Pseudomonas aeruginosa and Staphylococcus epidermidis. In addition, numerous isolates of Enterobacter and Enterococci were obtained from the animals. Positive blood cultures have often been observed in animals within 2-4 weeks following implantation of the devices. The similarities noted in this review suggest that the calf may be an appropriate animal model in which to study the pathogenesis of TAH-related infection.
Animals↗
Design mediated thrombus reduction in the Utah-100 total artificial heart.
The Utah-100 total artificial heart was initially designed and tested in 1983. General design goals, including improved fit for human application, improved reliability, and elimination of thrombus formation, were identified as improvements over the clinically used Jarvik-7 artificial heart, previously developed at the Institute for Biomedical Engineering, University of Utah. Specific design goals included 1) elimination of connector and valve-associated thrombus formation and 2) elimination of gross mineralization, thrombus formation, and creases on the blood-pumping diaphragm of the device. Explant retrieval results from 29 calves and sheep implanted with the Jarvik-7 artificial heart were compared with results from 25 calves and sheep implanted with the Utah-100 artificial heart. Macroscopic thrombus formation was found in 44% of the connectors of the Jarvik-7 artificial-hearts, compared with 2% (p less than or equal to 0.01) in animals with the Utah-100 artificial heart. Subvalvular and supravalvular thrombi were observed in 33% of the valves in the Jarvik-7 artificial heart and 10% (p less than or equal to 0.01) of the valves in the Utah-100 artificial heart. Mineralization of the pumping diaphragm was observed in 12% of the animals implanted with the Jarvik-7 artificial heart and in 4% of the animals with the Utah-100 diaphragms. Thrombus formation in the diaphragm-housing interface occurred in 2% of Jarvik-7 ventricles and in 6% of the Utah-100 ventricles. There were no identifiable diaphragm creases in the Utah-100 diaphragms, but a 10% incidence was found in Jarvik-7 devices. These results validate substantial progress toward improved design and fabrication methods in the Utah-100 total artificial heart.
Animals↗
In vitro analysis of an atrial shunt in balancing an electrohydraulic total artificial heart.
In vitro tests were performed to evaluate the use of an interatrial shunt in balancing a dual energy converter, actively filled, volumetrically coupled, electrohydraulic total artificial heart. The in vitro atrial shunt was comprised of a 8 mm (PTFE) Teflon graft placed between the left and the right atrium. Other features under study were 1) cardiac output (CO) response to preload, 2) CO relationship to mean aortic pressure, and 3) balance of ventricular outputs. The tests were performed by varying the right filling pressure and monitoring ventricular output and inflow/outflow pressures. Effects of changes in afterload were simulated by varying the (AoP) pressure from 80 mmHg to 120 mmHg, and the (PAP) pressure from 15 mmHg to 40 mmHg. The test results indicated a rise in CO from 4 L/min to 9 L/min, with a change in mean right atrial pressure from 0 mmHg to 12 mmHg. No significant difference in CO was found as afterload pressures were varied. The interatrial shunt (IAS) was effective in establishing ventricular balance over a wide range of preload and afterload conditions, and a mean positive flow from left to right was maintained in the atrial shunt, even at conditions simulating an extreme left-right imbalance.
Blood Flow Velocity↗
Factors influencing the accuracy of the cardiac output monitoring and diagnostic unit for pneumatic artificial hearts.
The Cardiac Output Monitor and Diagnostic Unit (COMDU) has been the most widely used method to noninvasively determine cardiac output in pneumatic ventricles for the past 10 years. Clinical observation has suggested a discrepancy between the COMDU and expected cardiac outputs. In vivo tests verified and quantified this error. The error sources were examined using in vitro test conditions, with both the inflow and outflow, as well as COMDU flow readings, being analyzed. Transducer and calibration error sources were also identified, and the accuracy of the method for determining cardiac output for the in vitro test conditions was quantified. With a more accurate calibration scheme, the in vitro average error was reduced from -16.2% (range of 0.1% to -41.1%) to 0.1% (range 4.8% to -3.65). The major error sources were identified as missed inflow, transducer calibration and drift, and system variance.
Animals↗
Right-left ventricular balance in implanted electrically powered artificial hearts.
An electrohydraulic total artificial heart (EHTAH), using an interatrial shunt (IAS) for right-left heart balance, was evaluated in acute, in vivo, open-chested calves. The EHTAH system demonstrated physiologic autoregulation with Starling-like responsiveness to preload. Output varied from 4 to 9 L/min, as right atrial pressure increased from 3 to 15 mmHg. Device output was minimally influenced by afterload. The efficacy of an IAS to balance the EHTAH was demonstrated over a wide range of preload and afterload conditions. Interatrial shunt flow rates, reflective of the degree of right-left imbalance, varied from 2% to 14% (IAS flow from left to right) of cardiac output. Left atrial pressures typically did not exceed right atrial pressures by more than 6-8 mmHg using an instrumented vascular graft such as the IAS. The simplicity and distinct anatomic, surgical, and engineering advantages of the IAS approach to right-left balance of implanted electrically powered artificial hearts justify further development toward a reliable long-term design.
Animals↗
Light scattering detection of microemboli in an extracorporeal LVAD bovine model.
Thromboembolization studies were performed on two calves supported by extracorporeal left ventricular assist devices (LVAD) using a light scattering (He Ne Laser) microemboli detector (LSMD). The LSMD system was placed on the outflow cannula of the LVAD in the extracorporeal loop of each animal. The measurements included the size, number, and rate of production of circulating microemboli in the range 20 microns less than microemboli diameter less than 1,000 microns. These data were compared to independently and concurrently obtained measurements of emboli shear rate (CPF), platelet count, red blood count (RBC), leukocyte count (WBC), plasma free hemoglobin, factors XIII, X, and V, and sorbitol dehydrogenase. Embolic number and volume were seen to be most dynamic in the very early phases of acute thromboembolization (0-40 minutes) with a peak embolic response within the first 30 minutes. The dynamics of reduced emboli volume, rather than number, may be implicated in the later stages of the thromboembolic passivation of these ventricles. The LSMD results generally showed an inverse correlation of microemboli volume rate with CPF measurements for each ventricle. LSMD, CPF, and leukocyte and platelet counts, showed a direct correlation with reduced counts for each additional ventricle for both calves. Factor XII was seen to have a more direct correlation in time with LSMD measurements for each ventricle than other parameters under investigation. This study represents the first time laser scattering and filtration methods have been applied simultaneously with hematologic assays in order to study the dynamics of device associated thrombogenesis.
Animals↗
Hemodynamic influence of LVAD on right ventricular failure.
Left ventricular assist device (LVAD) pumping has hemodynamic and anatomic influences on right ventricular performance. A total artificial heart (TAH) model was employed to better understand the hemodynamic influence of an LVAD on the failing right ventricle. Biventricular failure was simulated by reducing both ventricular drive pressures of the TAH. After getting hemodynamic data, LVAD pumping in the case of right ventricular failure was simulated by increasing just the left ventricular drive pressure. In the LVAD-simulating condition, cardiac output increased and right atrial pressure decreased significantly (p less than 0.05) compared with the biventricular failure condition, whereas right ventricular function and minute work were the same in these two conditions. Even though changes were accompanied by adaptive increases in pulmonary resistance, substantially lower pulmonary artery and left atrial pressures resulted in the LVAD-simulating condition. From a hemodynamic perspective, these results indicate that an LVAD can increase right ventricular volume work by decreasing right ventricular pressure work, whereas right ventricular net pressure-volume work is unchanged and right ventricular failure is not worsened.
Animals↗
The use of an artificial pericardium with a total artificial heart.
Postoperative adhesions following open heart surgery enhance the risks and increase the time of subsequent reoperation. When possible, primary closure of the natural pericardium is recommended, particularly in those cases that are more likely to be reoperated upon. The use of a total artificial heart (TAH) as a bridge to transplantation makes reoperation mandatory. If the pleura is left open to accommodate the ventricles, the risk of adhesion is considerable. To address this question, gluteraldehyde-fixed pericardial allografts were evaluated in calves undergoing TAH replacement. Eight animals were implanted with 3 different types of TAHs and survived from 12 to 108 days (mean 52.8 +/- 14.5). The pericardial substitute was wrapped around the TAH and the vascular grafts and cuffs. Two different surgical techniques were evaluated. At the time of autopsy, the presence of adhesions and gross epicardial reaction was macroscopically characterized and classified according to a standardized scale. Bacterial cultures were taken and tissue submitted for histology. The animals implanted with pericardial allografts for periods greater than 3 weeks were observed to have greater adhesions than those implanted for periods less than 3 weeks (p = 0.006). Pericardial cultures were negative in all cases and neovascularization and fibroplasia of the underlying tissues occurred in all cases. Leukocyte infiltration was minimal in the shorter term implant animals. Degeneration of a portion of the pericardium occurred in only 2 cases after 90 days. Minor calcification of the artificial pericardium was noted, but only in the longer term implant animals. The artificial pericardium reduced adhesion, thus facilitating reoperation in implants lasting up to a month.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Infections and thromboembolism with implantable cardiovascular devices.
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Animals↗
Heparin neutralization of antiplatelet effect of aspirin and dipyridamole.
Heparin is used as an anticoagulant for treatment or prevention of thromboembolism. Heparin has been shown also to 1) stimulate platelet aggregation and platelet release reaction, 2) enhance thromboxane A2 production in platelets, and 3) neutralize prostacyclin, a potent inhibitor of platelet aggregation. In the light of these observations, the effect of heparin on two commonly used antiplatelet agents, aspirin and dipyridamole, was investigated. It was noted that heparin reversed the antiplatelet effect of both aspirin and dipyridamole although the effect was relatively more pronounced with aspirin. Presence of aspirin in blood in vitro as well as in vivo resulted in the inhibition of release reaction and the secondary wave of platelet aggregation. In the presence of heparin, platelets previously treated with aspirin showed nearly normal platelet aggregation as well as the release reaction. This reversal by heparin of the inhibitory effect of aspirin was dose dependent; the neutralization of inhibitory effect being more pronounced as the concentration of heparin was increased at a given concentration of aspirin. The neutralization of antiplatelet effect of aspirin was observed in vitro as well as in vivo and whether heparin was added before or after the addition of aspirin. These observations suggest the need for caution in the event heparin and antiplatelet agents are administered concurrently.
5-Hydroxytryptophan↗
Enhanced bacterial adhesion on surfaces pretreated with fibrinogen and fibronectin.
The effect of certain plasma proteins on the adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis on polyurethane, polyvinylchloride, or glass was investigated. Test surfaces were treated with serum, plasma, albumin, immunoglobulin G, fibrinogen, or fibronectin. Using a specially designed test chamber, surfaces previously treated with test proteins were incubated with bacterial suspension. During the experiment, the test chamber was placed on a rotator to prevent settling of bacteria. At the end of the experiment, each test well was rinsed repeatedly to remove non-adherent bacteria. The number of bacteria adherent to the test surfaces was quantitated by a combination of methods including microscopic counting of cells, scintillation counting and autoradiography. It was noted that a greater number of bacteria adhered to surfaces coated with fibrinogen or fibronectin whereas surfaces treated with serum showed reduced bacterial adhesion. The inhibitory effect of serum appeared more pronounced with S. epidermidis when compared with P. aeruginosa under identical experimental conditions. Scanning electron microscopy revealed that adherent bacteria were randomly distributed on the test surfaces and appeared to replicate while still adherent. These observations suggested that bacterial adhesion to biomaterials can be significantly influenced by the composition of the adsorbed proteins at the interface.
Adsorption↗
A pulmonary mock circulation model for a better understanding of protamine reversal of heparin.
Neutralization of heparin by protamine is a common procedure following extracorporeal circulation (cardiopulmonary bypass) of blood. Protamine administration has been shown to cause serious hemodynamic derangement in some patients. Obstruction of the pulmonary vascular bed following protamine administration has been suggested to be the primary cause of hemodynamic changes. The present study was undertaken to test the hypothesis that macromolecular complexes formed between cationic protamine with anionic heparin or other plasma components cause the obstruction of the vascular bed. An in vitro mock circulation model was designed to examine the formation of such complexes. In this model, blood or plasma was passed through a glass bead column at a constant flow rate while the pressure between the syringe pump and the column was closely monitored. No increase in pressure was noted when blood, plasma or saline alone or with added heparin were passed through the column. Addition of protamine to either blood or plasma resulted in a significant increase in the pressure; this increase was even greater when heparin was also present in the test medium. That the increase in pressure was due to the obstruction of the column was confirmed by using 1251-protamine and documenting that complexes formed between protamine and plasma proteins/heparin were retained in the column. These observations suggested that protamine formed large insoluble complexes with plasma proteins. Heparin appeared to help consolidate these complexes thus causing a rapid increase in the pressure. This may explain why the hemodynamic changes following protamine administration are more pronounced in patients with circulating heparin.
Blood↗