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Biomedical subjects

D B Olsen

Publications and source records attributed to D B Olsen.

At least 163 records · Page 9Linked to original sources
PubMed1975

Survival for 18 days with a Jarvik-type artificial heart.

This is a report of an experiment wherein a calf had its natural heart replaced with an artificial heart and survived for 18 days and 20 hours. All measured physiologic parameters remained normal until the fourteenth day. Thereafter a gradual persistent rise in venous pressure and signs of a decreased cardiac output occurred. However, the animal outwardly appeared normal until the eighteenth day. During the nineteenth day it became comatose and was killed. At autopsy large thrombi were found in both atria, impairing ventricular filling, resulting in venous congestion and diminished cardiac output. This extended survival time and our ability to understand and eliminate the problems associated with artificial heart implantation give support to our hope that artificial hearts for man will be possible in the not too distant future.

Acute Kidney Injury↗
PubMed1975

Thrombus generation within the artificial heart.

The sites of thrombus formation in the Jarvik III artificial heart were studied in 20 consecutive calf experiments. Identical design and implantation procedures were used with two different surfaces. The 10 anticoagulated calves receiving Dacron-fibrilized silicone rubber surfaces survived an average of 296 hours. In contrast, the 10 nonanticoagulated calves with smooth poyurethane hearts survived 545 hours. The polyurethane surfaces were constantly clean. However, the rough surfaces were coated with variable amounts of thrombi. The sharp angle between the diaphragm and housing contained varying amounts of thrombi deposits in 75 per cent of the cases. Thrombe deposition occurred on 41 per cent of the valves. These thrombe were the source of emboli into the kidney, brain, and lungs. Turbulences and stagnation areas generated thrombus formation. Anticoagulation did not prevent thrombus formation. It would appear that heart free of turbulence and stagnation areas must be designed to eliminate thromboembolism.

Animals↗
PubMedDate not supplied

Pseudononapeptide bombesin antagonists containing C-terminal Trp or Tpi.

Seven new antagonists of bombesin (Bn)/gastrin-releasing peptide (GRP) containing C-terminal Trp or Tpi (2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-3-carboxylic acid) in a reduced peptide bond were synthesized by solid phase methods and evaluated biologically. The reduced bond in four [Leu13 psi(CH2NH)Trp14]Bn(6-14) analogs was formed by reductive alkylation at the dipeptide stage. In the case of three [Leu13 psi(CH2N)Tpi14]Bn(6-14) analogs, the Trp dipeptide with reduced bond was reacted with formaldehyde to form the corresponding Tpi derivative. These Tpi-containing analogs have a new reduced bond which is structurally more constrained. Leu13 psi(CH2N)Tpi14 analogs inhibit [125I][Tyr4]bombesin binding to Swiss 3T3 cells with IC50 values of 2-4 nM, compared to 5-10 nM for Leu13 psi(CH2NH)Trp14 analogs. Leu13 psi(CH2N)Tpi14 analogs are also more potent than Leu13 psi(CH2NH)Trp14 analogs in growth inhibition studies using Swiss 3T3 cells. The two best bombesin antagonists of this series, [D-Trp6,Leu13 psi(CH2N)Tpi14]Bn(6-14) (RC-3415) and [Tpi6,Leu13 psi(CH2N)Tpi14]Bn(6-14) (RC-3440), inhibited GRP-stimulated growth of Swiss 3T3 cells with IC50 values less than 1 nM. RC-3440 was also active in vivo, suppressing GRP(14-27)-stimulated serum gastrin secretion in rats. Bombesin/GRP antagonists, such as RC-3440, containing the new reduced bond (CH2N) reported herein are very potent.

3T3 Cells↗
PubMedDate not supplied

A comparison of the antiplatelet effect of aspirin on human and bovine platelets.

The risk of thromboembolism in human patients or animal models with blood contacting prosthetic devices is well documented. Aspirin is used frequently as an antiplatelet agent to minimize this risk. Although the inhibitory effect of aspirin on human platelets has been clearly established, preliminary studies to examine this effect on bovine platelets revealed a minimal inhibition of platelet function in vivo as well as in vitro. Because a considerable amount of implant research is carried out in bovine models, it was considered important to evaluate carefully the antiplatelet effect of aspirin on bovine platelets. To evaluate the effect of aspirin, experiments were conducted on human and bovine blood in vitro as well as after the administration of aspirin up to 4,000 mg/day (p.o.) in calves and 2,500 mg/day in humans. Appropriate amounts of buffered aspirin were added to heparinized or citrated blood incubated for 25 min and centrifuged to obtain platelet rich plasma (PRP). An aliquot of PRP was then challenged by a predetermined concentration of ADP (an aggregating agent) or collagen to evaluate platelet aggregation and release reaction. After aspirin was administered in vivo, blood was drawn from the animal at predetermined intervals to evaluate platelet function. In human blood, the inhibitory effect of aspirin was discernable at 80 mg/L in vitro and 2,500 mg/day when ingested orally. Under identical experimental conditions, no inhibition of bovine platelet aggregation was observed using dosages of aspirin up to 1,000 mg/L in vitro or 4,000 mg/day in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMedDate not supplied

Characterization of natural and total artificial heart acceleration.

The pulsatile nature of an implanted total artificial heart (TAH) may have several deleterious effects. To define the level of TAH impact, acceleration was measured and compared with that of the natural heart in a series of in vivo and in vitro experiments. In TAH implantations in calves, miniature accelerometers were incorporated onto the housing of a Utah-100 left ventricle. Identical accelerometers were glued to felt pledgets to obtain measurement of radial cardiac acceleration when sewn to the epicardial surface of the natural heart. Measurement of natural and artificial heart acceleration was made both intraoperatively and postoperatively in several animals. Many pumping conditions were also investigated with a similarly instrumented UVAD 85 left ventricle during in vitro testing. The peak natural heart acceleration measured was nearly 2 g both intraoperatively and at rest. Treadmill exercise or epinephrine infusion produced twice the resting peak acceleration value of the natural heart. Artificial heart peak acceleration as great as +/- 100 g was found intraoperatively and postoperatively. Peak TAH acceleration could be reduced by allowing the ventricle to fill fully prior to the start of the next systole, by allowing the ventricle to fully eject prior to the next diastole, or by using a ventricular pressurization waveform that has a smooth contour with a sinusoidal-like profile. The ability to lower TAH acceleration may lead to a reduction in undesirable consequences of TAH implantation.

Animals↗
PubMedDate not supplied

Characterization of blood microemboli associated with ex vivo left ventricular assist devices in a bovine model.

An ex vivo left ventricular assist device (LVAD) model was used in calves to study the production of blood microemboli (BME) and to evaluate possible correlations between constant-pressure filtration (CPF) measurements of flow-resistant BME, light-scattering microemboli detection (LSMD), observable thrombus accumulation, and hematologic markers. Aortic LVAD cannulae were implanted through the chest wall in two calves, and each calf received a series of LVADs, each operating 1-4 days. Blood samples from the LVADs underwent CPF through 20 mu pore filters at 20 mm Hg to produce estimates of occlusive BME concentration. Laser (He-Ne) light was directed through the outflow cannula, and the differentially-scattered light was detected for computer estimation of microemboli size, volume, and frequency. Blood chemistry and coagulation parameters were also analyzed. Removed LVADs were examined with polar coordinate mapping of accumulated perivalvular thrombi. One ventricle produced significantly greater CPF results, LSMD results, and Factor XII levels. During the use of that ventricle, the CPF results increased slowly with time after LVAD connection, while the LSMD results and Factor XII levels increased immediately after connection, followed by a later decrease. This contrast is explainable in terms of the dynamic development of BME strength. The calf model appears useful for the study of thrombogenesis, and the CPF and LSMD methods of BME analysis complement each other, and other measurements.

Animals↗
PubMedDate not supplied

Immobilized albumin-immunoglobulin G for improved hemocompatibility of biopolymers.

Efforts to render blood contacting surfaces less thrombogenic have included chemical modification of the polymer, as well as surface modifications with proteins, anticoagulants, or antiplatelet agents. Studies reported from this laboratory in the past have shown that certain surfaces pretreated with albumin-Immunoglobulin G (alb-IgG) become relatively more hemocompatible (reduced platelet adhesion, minimal thrombus). However, absorbed proteins, including alb-IgG, desorb rapidly when exposed to circulating blood. Therefore, efforts were made to immobilize alb-IgG on glass or Biomer as follows: a 2 mg/ml solution of IgG was crosslinked with glutaraldehyde on the test surface. Crosslinked IgG was then treated with mercaptoethanol to reduce the disulfide bonds, followed by incubation with albumin previously reduced with mercaptoethanol under conditions that allowed reassociation of disulfide bridges between albumin and crosslinked IgG. Alb-IgG immobilized at the test surface following this method was found to remain at the interface when the surface was exposed to blood in vitro for up to 7 days under static conditions. Glass or Biomer surfaces with crosslinked Alb-IgG showed considerable reduction in the adhesion of 111In-platelets and adsorption of 125I-fibrinogen when test surfaces were analyzed in a flow chamber. Under identical experimental conditions, surfaces with crosslinked albumin alone were not effective in reducing the adhesion of platelets. Crosslinked IgG or immobilization of IgG on crosslinked albumin following the above methods rendered the surfaces more thrombogenic. It was noted, however, that crosslinked proteins on Biomer were dislodged rapidly in areas with turbulent flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Scanning and transmission electron microscopic evaluation of the U-100 total artificial heart blood contacting surface.

Thrombus formation, cell adhesion, mineralization, and the adsorbed protein layer have been investigated on blood contacting surfaces of the Utah-100 total artificial heart (TAH). Retrieval analysis was performed on two calves (at 7 and 97 days) and a sheep (at 21 days). Six locations on each ventricle were systematically evaluated by scanning electron microscopy. Transmission electron microscopy was used to measure the thickness and distribution of proteins (albumin, IgG, and fibrinogen) on the surface. Gross thrombus was detected only on the left atrial cuff in the 97 day calf. SEM demonstrated fairly clear surface morphology, with minimal platelet adhesion and activation, and little thrombus formation. At 97 days, calcium deposits were detected along the diaphragm-housing junction. Protein layer thickness on the diaphragm increased with implant time; dominant proteins detected on the surface were fibrinogen and IgG, rather than albumin. Improvements in design and fabrication techniques have demonstrated decreased intradevice thrombosis with the U-100 TAH. However, systemic thromboembolism still remains a problem, and further improvements in the blood contacting surface of the U-100 TAH are necessary to achieve a thrombus free TAH.

Animals↗
PubMedDate not supplied

An in vitro test model to study the performance and thrombogenicity of cardiovascular devices.

During the development of cardiovascular devices, it is necessary to evaluate their performance in vitro under experimental conditions that closely resemble their use in vivo. Therefore, an in vitro test model was developed to evaluate the performance of cardiovascular devices with blood. The in vitro test model consists of a pneumatically driven 50 cc polyurethane ventricle with either mechanical or experimental polyurethane tricuspid semilunar valves, connected to a horseshoe-shaped blood reservoir. A sampling port permits frequent removal of blood for hematologic evaluation. All the couplings are of the quick connect type to facilitate assembly and exchange of parts. The total volume of blood in the test model is approximately 1.4 L, and experiments are conducted in the absence of an air-blood interface. Except for mechanical valves and the chosen test interface, the entire blood contacting surface consists of polyurethane. Fresh bovine heparinized blood is used for the experiments. After filling the reservoir and the ventricle with blood, the concentration of heparin is adjusted with protamine to an APTT level of three times normal (80-100 sec). Once this level of anticoagulation is achieved, the blood is circulated for the next 2-3 hr at the desired test parameters (beats/min, cardiac output, etc.). A number of hematologic parameters are monitored during the test, including APTT, PT, plasma free hemoglobin and ADP-induced platelet aggregation. With the help of this model a number of devices, including experimental polyurethane tricuspid semilunar valves, Silastic tube valves, valves with heparin coated leaflets, and small (50 cc) experimental ventricles have been studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Mechanical failures of the pneumatic Utah-100 and Jarvik total artificial hearts. A comparative study.

Jarvik-5 and Jarvik-7 total artificial hearts (TAHs) and Utah-100 TAHs were fabricated and implanted in calves and sheep. In the Jarvik series, 30.7% had mechanical failures (16.1% catastrophic). In the Utah-100 TAH series, 11.1% had mechanical failures (3.7% catastrophic). Failures were classified as: 1) diaphragm failures; 2) valve-holding ring failures; 3) air-leak failures; and 4) prosthetic valve failures. Marked reduction in mechanical failure for the Utah-100 TAH is attributed to progressive component redesign, material selection, and more stringent quality control criteria.

Animals↗
PubMedDate not supplied

Immune response changes with blood pump use in calves.

Device-related bacterial infections are a significant deterrent to the long-term implantation of the total artificial heart (TAH). Device-related infections in the calf are caused by the same spectrum of organisms, over approximately the same time course, as those reported in man. We studied immunologic function in two groups of 3-4 month old, Holstein steer calves; four animals underwent cardiopulmonary bypass (CPB) only and seven calves underwent CPB and TAH implantation. There was a transient rise in total white blood cell counts and a transient fall in the hematocrit following the procedures in each group. Absolute numbers of neutrophils in the TAH group declined to near or below preoperative levels by the end of the 1 month study period. There was a transient increase in chemotactic response of isolated neutrophils to bovine C5a immediately following CPB and increased hydrogen peroxide production on postoperative day 3. Hydrogen peroxide levels were elevated in the TAH animals from postoperative day 14 to the end of the study period. Serum immunoglobulin levels of IgG, IgM, and IgA did not change significantly during the study period in the TAH group. IgG levels were elevated after week 3 in the CPB group.

Animals↗
PubMedDate not supplied

Microbiologic survey of prosthetic blood pumps presterilization and poststerilization and at explant retrieval.

Device-associated infection remains a major complication of implanted total artificial hearts (TAH). The possibility of microbes being introduced on the device was investigated by conducting a gross microbial assay, pre- and poststerilization, and following explant retrieval. Culture samples were obtained from the housing, base, and blood-contacting diaphragm of Utah-100 artificial ventricles. Additional samples were obtained from atrial sewing cuffs, outflow grafts, drive lines, and percutaneous leads, along with reference control samples prior to ethylene oxide sterilization (ETO). Culturing was repeated poststerilization and at device explant retrieval. Positive bacterial and fungal cultures were found in 24% of the presterilization samples; in the poststerilization samples, positive cultures were found in 6%. Following device explant retrieval, 84% of the cultures were positive. The reference control samples were positive in a limited number of the poststerilization samples. There was no correspondence of the species of micro-organisms found at the same location for each sampling condition. These data demonstrate that the surfaces of the TAH can become contaminated during fabrication. The presence of microbial activity poststerilization raises the possibility of inadequacy of the ETO protocol used with these devices, or contamination of the surgical field. Hearts at explant retrieval had cultures positive for microbes differing from those identified prior to implantation. This finding suggests that device-associated micro-organism colonization occurs through a source other than manufacturing or surgical contamination.

Animals↗