Biomedical subjects

D B Olsen

Publications and source records attributed to D B Olsen.

At least 181 records · Page 10Linked to original sources

PubMedDate not supplied

Sensitivity of the artificial heart to changes in vascular resistance.

For conditions near those for normal operation, the cardiac output of the healthy natural heart is inherently sensitive to systemic venous resistance but is relatively insensitive to arterial resistance. A mathematical comparison was undertaken to discover the differences in the sensitivity of two configurations of artificial hearts to these resistances. It was found that one design incorporating independently pumping ventricles can be tailored to passively mimic the sensitivity of the natural heart. However, the other design with volumetrically coupled pumping is incapable of exhibiting similar sensitivity through passive means.

Equipment Design↗

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Correlation of gross and microscopic appearance of skin buttons in total artificial heart animals.

Pneumatic artificial hearts are powered by compressed air that is delivered through percutaneous tubes. A stress relief device, termed a skin button, surrounds these tubes as they exit from the recipient's tissues. The skin button is designed to protect the tissues from damage and provide a secure material-tissue interface. Prevention of superficial and invasive infection is the primary goal of the skin button. Eight calves were studied prospectively to identify gross or microscopic infection with the skin button. All animals who survived more than sixty days (62-136) had both gross and microscopic evidence of infection. All animals surviving less than 60 days (13-43) had no gross evidence of infection but one had subcutaneous microscopic abscess formation. No animal died secondary to a skin button infection. Skin buttons cannot prevent infection but they can contain the pathologic process in the superficial tissues with no evidence of systemic effects.

Animals↗

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A blood pump with an interatrial shunt for use as an electrohydraulic total artificial heart.

A recently designed blood pump subsystem for the completely implantable electrohydraulic total artificial heart (EHTAH) has been developed and is under evaluation. The subsystem consists of joined left and right ventricles, atrial cuffs with an interatrial shunt (IAS), and two outflow grafts. The ventricles were developed to fit within the pericardial space based on the results of anatomic fit trials. An optimized configuration for animal use, which was adaptable for human use with minimal modification, was identified. The core dimensions of the ventricles with an energy converter are approximately 10 x 11 x 7 cm. Maximum output and stroke volume are 9.2 L/min and 81 ml, respectively. The IAS is used to balance the volumetrically coupled EHTAH, and is made by forming an orifice in the common septum of the left and right atrial cuffs. Performance and durability of the IAS were examined in animal experiments for up to 9 days. The diameter of the IAS was 3.4-5.5 mm, and the left-right atrial pressure difference ranged from 2 to 10 mmHg, with 0.57-1.48 L/min of theoretically calculated shunt flow. No evidence of thrombus formation was found in or around the IAS at autopsy. The entire EHTAH system with a new blood pump is being assembled for long-term animal studies.

Animals↗

PubMedDate not supplied

Development of a totally implantable artificial heart.

The first generation of an integrated, totally implantable electrohydraulic total artificial heart was designed for long-term cardiac replacement. The system consists of an elliptical blood pump with an interatrial shunt, Medtronic-Hall 27 mm and 25 mm inflow and outflow valves, respectively, an energy converter consisting of an axial-flow, hydraulic pump driven by a brushless DC motor, and an electronics system with transcutaneous energy transmission and telemetry. Energy is supplied by internal nickel-cadmium rechargeable batteries that supply power for 20 min and external silver-zinc batteries that are designed to supply energy to run the system for 5 hr. The blood pump consists of a single layer diaphragm cast from Biolon, with joined right and left ventricles sharing a common base. The dynamic stroke volume is 84 ml, and maximum cardiac output is 9.2 L/min at a heart rate of 110 beats/min on the mock circulation. A 4.3 mm diameter interatrial shunt is used to balance the volumetrically coupled ventricles. The energy converter pumps hydraulic fluid alternately between ventricles, with controlled, active filling in one ventricle during the systolic phase of the other ventricle. Internal or external controllers adjust the heart rate and motor speed to maintain normal atrial filling pressures and full stroke. Electromagnetic induction is used to transfer energy through the skin and a bidirectional infrared data link incorporated within the transcutaneous energy transmission coils is used to transmit information. The entire system is being assembled and refined for long-term animal implant studies.

Algorithms↗

PubMedDate not supplied

Anaerobic threshold in total artificial heart animals.

The anaerobic threshold represents an objective measure of functional capacity and is useful in assessment of pulmonary and cardiovascular dysfunction. This study determined the anaerobic threshold in total artificial heart animals and evaluated the performance of the total artificial heart system. Five animals with total artificial hearts were put under incremental exercise testing after exercise training. The intensity of exercise ranged from 2.0 to 4.5 km/hr, with an increment of 0.5 km/hr every 3 min. The anaerobic threshold was 6.72 +/- 0.84 ml/kg/min as detected by the lactate method, and 6.48 +/- 0.79 by the CO2 method. The value of the anaerobic threshold in total artificial heart animals implies that the performance capacity of a total artificial heart is not sufficient to meet the oxygen requirements of vigorously exercising skeletal muscle. The protocol does not allow for driving parameter changes during exercise, and this situation, combined with the manual mode of the control system used, was inadequate to allow the total artificial heart animals to exercise more vigorously. Using an automatic control mode might be helpful, as well as considering the relationship between indices of oxygen metabolism, such as oxygen delivery, oxygen consumption, and oxygen extraction rate, in the control algorithms in total artificial heart control systems.

Anaerobic Threshold↗

PubMedDate not supplied

Oxygen metabolism in animals with total artificial hearts.

The relationship between indices of oxygen metabolism has been widely used in clinical practice to evaluate the adequacy of tissue perfusion, to predict the outcome of the critically ill patient, and to evaluate the effectiveness of therapies. This study quantitated and correlated the relationship between oxygen delivery (DO2), oxygen consumption (VO2), and oxygen extraction rate (EO2) in 14 animals with total artificial hearts (TAH) to investigate the oxygen metabolism in animals with TAH during different physiologic and pathologic conditions. These 14 animals were subdivided into healthy, critical, and exercise groups. There was a physiologic dependence of DO2 to VO2 in animals in the healthy and exercise groups, whereas a pathologic dependence of VO2 to DO2 appeared to occur in animals in the critical group. Reduced or inadequate VO2 leads to organ dysfunction, shock syndrome, multiple organ failure, and finally, mortality. Providing a higher level of DO2 by restoring circulating blood volume, increasing cardiac output, raising hematocrit levels, and improving pulmonary function to achieve a higher level of oxygen extract efficiency and oxygen consumption in animals with TAH that are in a critical condition might be helpful for the treatment of complications and result in decreasing mortality. Using the relationship between indices of oxygen metabolism as a physiologic modifier for TAH control algorithms also might improve the physiologic performance and quality of life of TAH recipients.

Animals↗

PubMedDate not supplied

Markers of thromboembolization in a bovine ex vivo left ventricular assist device model.

The production of blood microemboli (BME) was studied using an ex vivo exteriorized left ventricular assist device (LVAD) model in calves. Each of eight calves received a series of three LVADs, each operating for 24 hr. Blood microemboli were measured directly by a laser (624 nm and 828 nm) light scattering microemboli detection (LSMD) system through the LVAD outflow cannula and by constant pressure filtration (CPF) of blood samples from the LVAD outflow cannula. Hematologic parameters were also measured. After LVAD removal, perivalvular thrombi were evaluated using polar coordinate mapping. The average LSMD and CPF results correlated. For example, in one series of three calves, one ventricle exhibited significantly greater thrombogenesis than did the other ventricles, as indicated by both the LSMD and CPF results. In a series of five calves, one calf developed an abnormally high activated thromboplastin time (APTT), even in the absence of heparin. For two of the three ventricles tested in that calf, microemboli concentration (CPF), Factor XII activity, level of fibrin degradation products (FDP), and accumulated thrombus were significantly lower than for the other calves. The whole blood viscosity (WBV, at 230 s-1) in this calf also decreased to lower values than were seen with the other calves.

Animals↗

PubMedDate not supplied

Noninvasive diagnosis of mechanical failure of the implanted total artificial heart using neural network analysis of acoustic signals.

Acoustic signal measurement has been proposed as a noninvasive method of detecting mechanical failure of the implanted total artificial heart. However, differences in acoustic spectra obtained from undamaged and damaged devices may be difficult to distinguish using standard techniques, such as visual inspection or statistical analysis. A new technique, artificial neural network analysis, which has been used successfully on other problems of pattern recognition and classification, was applied to improve the detectability of the acoustic method. Acoustic signals were measured using two different devices in one damaged and one undamaged electrohydraulic total artificial heart, both in a mock circulation set-up and in animal experiments where they were implanted in eight post mortem sheep and the acoustic signal measured using a microphone placed at the skin surface. Spectra of the acoustic waveforms were calculated by discrete Fourier transformation and 400 values (representing the log magnitude in each 2.5 Hz band of the spectrum between 0 and 1 kHz) and used as input to the neural network. A three layer backpropagation neural network containing 400 input nodes, 20 intermediate nodes, and one output node was able to forms. The trained neural network then perfectly distinguished damaged waveforms from undamaged ones, with good separability. Because the neural network's output can take on a value between two extremes denoting damaged and undamaged states, it is possible to detect any progressive failure at relatively earlier stages. With multiple output node configuration, it could also classify the different types of damage using single acoustic signal waveforms.

Acoustics↗

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In vitro characterization of a magnetically suspended continuous flow ventricular assist device.

A magnetically suspended continuous flow ventricular assist device using magnetic bearings was developed aiming at an implantable ventricular assist device. The main advantage of this device includes no mechanical wear and minimal chance of blood trauma such, as thrombosis and hemolysis, because there is no mechanical contact between the stationary and rotating parts. The total system consists of two subsystems: the centrifugal pump and the magnetic bearing. The centrifugal pump is comprised of a 4 vane logarithmic spiral radial flow impeller and a brushless DC motor with slotless stator, driven by the back emf commutation scheme. Two radial and one thrust magnetic bearing that dynamically controls the position of the rotor in a radial and axial direction, respectively, contains magnetic coils, the rotor's position sensors, and feedback electronic control system. The magnetic bearing system was able to successfully suspend a 365.5g rotating part in space and sustain it for up to 5000 rpm of rotation. Average force-current square factor of the magnetic bearing was measured as 0.48 and 0.44 (kg-f/Amp2) for radial and thrust bearing, respectively. The integrated system demonstrated adequate performance in mock circulation tests by providing a 6 L/min flow rate against 100 mmHg differential pressure at 2300 rpm. Based on these in vitro performance test results, long-term clinical application of the magnetically suspended continuous flow ventricular assist device is very promising after system optimization with a hybrid system using both active (electromagnet) and passive (permanent magnets) magnet bearings.

Biomechanical Phenomena↗

PubMedDate not supplied

Pulsatile operation of a centrifugal ventricular assist device with magnetic bearings.

A prototype bench top model of a continuous flow ventricular assist device using an impeller suspended by magnetic bearings has been developed. Generation of a pulsatile pressure was studied using both a computer model and in vitro loop tests of the prototype. The motivation for developing a computer model for a blood pump in the natural circulation is two-fold. First, it allows simulation of the pump under a large variety of operating conditions. Second, it provides insight into what parameters of the system design are important for achieving a specific result. For example, in one case, an aortic pressure of 118/87 mmHg was generated by varying the speed from 2,000 to 2,600 rpm. The computer model was verified by coupling the centrifugal pump prototype to a mock circulatory system. The results of the model were verified by generating an aortic pressure of 113/78 mmHg while varying the speed from 2,000 to 2,600 rpm. These experiments have shown that it is possible to generate pulsatile pressure similar to that of native physiology using a centrifugal left ventricular assist device. Further tests will be required to quantify the effects on hemolysis.

Biomedical Engineering↗

PubMedDate not supplied

Control of the artificial heart.

The artificial heart (AH) is devoid of physiologic connections to the recipient's native feedback control loops. Control of an AH can be either passive or dynamic. Passive intrinsic control provides limited AH response to physiologic demands. Dynamic control requires the sensing of metabolic and hemodynamic signals and their incorporation into self-adjusting AH function. A single metabolic or hemodynamic parameter cannot provide sufficient data accurately to adjust AH pumping in response to varying blood flow demands. A combination of input control signals is required for reliable and flexible AH function. The selection of appropriate input control parameters and their incorporation into AH controller designs remains a critical step in the achievement of a permanent, totally implantable AH.

Heart Failure↗

PubMedDate not supplied

Implantable centrifugal pump with hybrid magnetic bearings.

Test methods and results of in vitro assessment of a centrifugal pump with a magnetically suspended impeller are provided. In vitro blood tests have been completed with a resulting normalized milligram index of hemolysis (NmIH) of 12.4 +/- 4.1, indicating that hemolysis is not a problem. Hydraulic characterization of the system with water has shown that a nominal pumping condition of 6 L/min at 100 mmHg was met at 2,200 rpm. Maximum clinically usable cardiac output is predicted be 10 L/min. The magnetic bearing supported impeller did not contact the housing and was shown to be stable under a variety of pumping conditions. The driving motor efficiency is 75% at the nominal condition. Finally, a description of the clinical version of the pump under development is provided.

Heart-Assist Devices↗

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Myocardial mechanics, energetics, and hemodynamics during intraaortic balloon and transvalvular axial flow hemopump support with a bovine model of ischemic cardiac dysfunction.

Unlike the mechanisms of intraaortic balloon pump (IABP) support, the mechanisms by which transvalvular axial flow Hemopump (HP) support benefit dysfunctional myocardium are less clearly understood. To help elucidate these mechanisms, hemodynamic, metabolic, and mechanical indexes of left ventricular function were measured during conditions of control, ischemic dysfunction, IABP support, and HP support. A large animal (calf) model of left ventricular dysfunction was created with multiple coronary ligations. Peak intraventricular pressure increased with HP support and decreased with IABP support. Intramyocardial pressure (an indicator of intramyocardial stress), time rate of pressure change (an indicator of contractility), and left ventricular myocardial oxygen consumption decreased with IABP and HP support. Left ventricular work decreased with HP support and increased with IABP support. During HP support, indexes of wall stress, work, and contractility, all primary determinants of oxygen consumption, were reduced. During IABP support, indexes of wall stress and contractility were reduced and external work increased. These changes were attributed primarily to changes in ventricular preload, and geometry for HP support, and to a reduction in afterload for IABP support. These findings support the hypothesis that both HP and IABP support reduce intramyocardial stress development and the corresponding oxygen consumption, although via different mechanisms.

Animals↗

PubMedDate not supplied

Numerical studies of blood shear and washing in a continuous flow ventricular assist device.

The third prototype of a continuous flow ventricular assist device (CF3) is being developed and tested for implantation in humans. The blood in the pump flows through a fully shrouded four bladed impeller (supported by magnetic bearings) and through small clearance regions on either side of the impeller. Computational fluid dynamics (CFD) solutions for this flow have been obtained by using TascFlow, a software package available from AEA Technology, UK. These flow solutions have been used to estimate the shear stresses on the blood in the pump and, hence, to minimize hemolysis. In addition, the solutions are informative for achieving a design that will provide good washing of the blood to minimize the possibility of stagnation points that can lead to thrombosis. This study presents numerical studies of these phenomena in the CF3. The calculated shear rate results are compared with values published in the open literature. The comparisons indicate that hemolysis will not be a problem with CF3, which is in agreement with preliminary experimental measurements. Flow studies are being conducted to determine the optimal size of the clearance regions.

Blood Flow Velocity↗

PubMedDate not supplied

Complications common to ventricular assist device support are rare with 90 days of DeBakey VAD support in calves.

The DeBakey VAD is a miniaturized, electromagnetically driven axial flow pump intended for long-term ventricular assist. Safety and performance data from six calves implanted with the complete DeBakey VAD system are reported elsewhere; here we describe complications and necropsy findings for these same six animals, all of which survived 90 days. The study was conducted according to a uniform protocol, which included anticoagulation and antibiotic prophylaxis. Clinical complications tracked included bleeding, cardiovascular abnormalities (e.g., arrhythmias, tachycardia unrelated to pain, bradycardia), hemolysis, hepatic dysfunction, renal dysfunction, thromboembolism (neurologic or peripheral), or infection. Each adverse event was retrospectively categorized with regard to severity (mild, moderate, severe) and relationship to device. Clinical findings were confirmed by necropsy. There was no evidence of systemic infection, thromboembolism, hemolysis, or renal or hepatic dysfunction in these six animals during the study period. A single adverse event was noted in each of two of the calves. Both events were considered mild according to the predefined criteria. Bleeding related to the surgical implantation procedure and requiring reoperation occurred in one animal. The other animal had evidence of a superficial infection at the exit site of the cables on the left lateral thoracic wall; the infection did not extend into the thoracic cavity. Chronic, healed small renal infarct scars were present in several animals. Mild valvular endocardiosis was observed in two calves and mild fibroelastosis was present in the endocardium at the site of the inflow cannula in three calves; however, these lesions were not considered clinically significant. No other gross or histologic abnormalities were noted at necropsy. In conclusion, calves implanted with the complete DeBakey VAD for 90 days demonstrated few complications and had no significant necropsy findings. Complications common to ventricular assist device (VAD) support (i.e., hemolysis, infection, bleeding, thromboembolism) were rare during long-term support (90 days) with the DeBakey VAD.

Animals↗

PubMedDate not supplied

Anesthesia and cardiopulmonary bypass technique in calves and sheep.

The number of research institutions using calves and sheep as models for open heart surgical procedures is increasing. The Artificial Heart Laboratory of the University of Utah has developed an effective protocol for thoracic procedures in these animals. Routine barbiturate induction and maintenance with fluothane and a pressure-regulated ventilator have minimized anesthetic problems. A membrane oxygenator with blood flows of 50 to 75 ml/kg body weight/min. seems to give adequate circulatory support during heart-lung bypass. Although animals implanted with total artificial hearts do not have problems with arrhythmias, changes in pulmonary function and peripheral vascular tone can alter their cardiac performance. The judicious use of ventilatory support and specific vasoactive drugs can significantly improve the animal's intraoperative blood pressure and postoperative arterial gases. A summary of the techniques and drugs which were used successfully in 187 of 189 animals during a 2 year period are presented.

Anesthesia, Intravenous↗

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Animal implantation results with the Utah-100 total artificial heart.

The Utah-100 total artificial heart was designed to have increased reliability over the Jarvik-7 total artificial heart, achieve better fit, and minimize device associated thrombus formation, without decreasing the function. The Utah-100 heart was tested in 28 calves and 3 sheep. The smallest animal at the time of implantation weighted 54 kg. Mean survival duration was 78 days (range, 1-331 days), with 14 animals surviving longer than 60 days. Multiple organ function was maintained satisfactorily with the Utah-100 artificial heart, and mean plasma free hemoglobin values in the calves that survived longer than 100 days were less than 10 mg/dl. Hemorrhage was the main cause of death in animals dying within 30 days after implantation (5/13, 38%); infection was another primary cause of death or termination (4/31, 13%). Deaths due to mechanical failure occurred from valve or diaphragm failure in two cases, yielding a 91% reliability at a 90% confidence level for 60 days' support. No animal died because of driver or other technical failure. Utah-100 hearts showed superior antithrombogenicity in the connector and valve-related areas when compared with the results of the Jarvik-7 heart, which was also fabricated and implanted in our laboratory (p less than 0.01). With these test results, the authors anticipate that the Utah-100 heart will be a safe and effective device for interim use as a bridge to heart transplantation.

Animals↗

PubMedDate not supplied

Potent agonists of growth hormone-releasing hormone. II.

Analogs of the 29-amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) or Lys-NH2 in position 29 have been synthesized by the solid-phase method, purified, and tested in vitro. Except for one peptide, all analogs contained desaminotyrosine (Dat) in position 1. All contained Nle27 in order to avoid oxidation of Met27. Some peptides contained one or more additional L- or D-amino acid substitutions in positions 2, 12, 15, 21, 27 and/or 28. Analogs [Dat1, Ala15, Nle27, Asn28]GH-RH(1-28)Agm (II, [Asn28]-Mz-2-51); [Dat1, Ala15, D-Lys21, Nle27, Asn28]GH-RH(1-28)Agm (III, MZ-3-125); and [Dat1, D-Asn8, Ala15, D-Lys21, Nl27, Asn28]GH-RH(1-28)Agm(IV, MZ-3-129) were 5.7, 2.8, and 3.9 times more potent in vitro, respectively, than GH-RH(1-29)NH2. However, if we compare the potencies of peptides II and III (analogs of the bovine sequence) with those of the analogs of human GH-RH (XII and XIII) [Dat1, Ala15, Nle27]GH-RH(1-28)Agm; [Dat1, Ala15, D-Lys21, Nle27]GH-RH(1-28)Agm, respectively, the GH-releasing potency was decreased by 50% and 33%, respectively, by the incorporation of Asn28. Our studies indicate that Lys-NH2 at the C-terminus of GH-RH(1-29) and/or beta-Ala, GABA (gamma-aminobutyric acid), and Phe in position 15 are disadvantageous, but potent GH-RH analogs can result from the combination of agmatine in position 29 with other substitutions.

Amino Acid Sequence↗