Biomedical subjects

M R Müller

Publications and source records attributed to M R Müller.

At least 37 records · Page 2Linked to original sources

PubMed1997

Thrombin augments vascular cell-dependent migration of human mast cells: role of MGF.

Recent data suggest that auricular thrombosis is associated with accumulation of mast cells (MC) in the upper endocardium (where usually no MC reside) and local expression of MGF (mast cell growth factor) (25). In this study, the role of vascular cells, thrombin-activation and MGF, in MC-migration was analyzed. For this purpose, cultured human auricular endocardial cells (HAUEC), umbilical vein endothelial cells (HUVEC) and uterine- (HUTMEC) and skin-derived (HSMEC) microvascular endothelial cells were exposed to thrombin or control medium, and the migration of primary tissue MC (lung, n = 6) and HMC-1 cells (human MC-line) against vascular cells (supernatants) measured. Supernatants (24 h) of unstimulated vascular cells (monolayers of endocardium or endothelium) as well as recombinant (rh) MGF induced a significant migratory response in HMC-1 (control: 3025 +/- 344 cells [100 +/- 11.4%] vs. MGF, 100 ng/ml: 8806 +/- 1019 [291 +/- 34%] vs. HAUEC: 9703 +/- 1506 [320.8 +/- 49.8%] vs. HUTMEC: 8950 +/- 1857 [295.9 +/- 61.4%] vs. HSMEC: 9965 +/- 2018 [329.4 +/- 66.7%] vs. HUVEC: 9487 +/- 1402 [313.6 +/- 46.4%], p < 0.05) as well as in primary lung MC. Thrombin-activation (5 U/ml, 12 h) of vascular cells led to an augmentation of the directed migration of MC as well as to a hirudin-sensitive increase in MGF synthesis and release. Moreover, a blocking anti-MGF antibody was found to inhibit MC-migration induced by unstimulated or thrombin-activated vascular cells. Together, these data show that endocardial and other vascular cells can induce migration of human MC. This MC-chemotactic signal of the vasculature is associated with expression and release of MGF, augmentable by thrombin, and may play a role in the pathophysiology of (auricular) thrombosis.

Blotting, Northern↗

PubMed1997

DNA repair and cellular resistance to alkylating agents in chronic lymphocytic leukemia.

The time course of the formation and persistence of repair-induced DNA lesions such as single-strand breaks (SSBs) were determined in isolated lymphocytes derived from 32 patients with chronic lymphocytic leukemia (CLL) using the single-cell gel electrophoresis (SCGE, "comet") assay. After pulse-exposure to N-ethyl-N-nitrosourea (EtNU), the initial amount of SSBs (t0 SCGE values) and the time periods required to reduce DNA damage by 50% (t50% SCGE values) were determined in nuclear DNA of individual cells. The t0 SCGE and t50% SCGE values varied interindividually between CLL specimens by factors of 16.6 and 8.2, respectively. Regarding cell-to-cell variation, no major subpopulations with significantly different DNA repair capacities were observed in cell specimens from a given patient. In addition, a monoclonal antibody-based immunocytological assay was used to determine the elimination kinetics for the cytotoxic alkylation product O6-ethylguanine from nuclear DNA. A strong correlation was observed between the relative times for SSB repair and the elimination of O6-ethylguanine from nuclear DNA. Because SCGE and immunocytological assay measure different steps of DNA repair, this observation suggests coordinated regulation of the respective repair pathways. With regard to chemosensitivity profiles, a "fast" repair phenotype corresponded to enhanced in vitro resistance to EtNU, 1,3-bis(2-chloroethyl)-1-nitrosourea, or chlorambucil. Accelerated SSB repair and pronounced in vitro resistance to chlorambucil, 1,3-bis(2-chloroethyl)-1-nitrosourea, and EtNU were found in lymphocytes from CLL patients nonresponsive to chemotherapy with alkylating agents. Distinct DNA repair processes thus mediate resistance to alkylating agents in CLL lymphocytes.

Antineoplastic Agents, Alkylating↗

PubMed1996

Structural quantification and bifurcation symmetry in arterial tree models generated by constrained constructive optimization.

Arterial tree models are generated by Constrained Constructive Optimization according to minimum intravascular volume. These models, which have been shown to adequately reproduce pressure profiles and branching angles, are analysed topologically and geometrically in order to investigate how structure influences the functional capabilities. Therefore, the number of bifurcation levels and STRAHLER orders was evaluated for the complete trees as well as for subtrees of all possible sizes. Bifurcation symmetry, being a particular aspect of structure, was found to be higher in the smaller than in the larger subtrees. This confirms a more delivering type of function for the small subtrees, as expected from intuitive arguments. Conversely, lower symmetry in larger subtrees relates to their conveying type of function. Moreover, different shapes of the tissue to be perfused lead to different symmetry properties of optimized tree models.

Algorithms↗

PubMed1996

Modulation of multidrug resistance by BIBW22BS in blasts of de novo or relapsed or persistent acute myeloid leukemia ex vivo.

The phenylpteridine derivative BIBW22BS (BIBW22) is a potent modulator of multidrug resistance (MDR). We investigated BIBW22 in comparison to dexniguldipine and verapamil as modifier of MDR in blasts of de novo, relapsed or persistent acute myeloid leukemia (AML) in vitro. All patients with relapsed or persistent AML had been pretreated with idarubicin and cytosine arabinoside. The degree of MDR was determined by efflux kinetics of rhodamine 123 (R123), daunorubicin, and idarubicin measured by flow cytometry (FACS). A total of 51 patients with AML, 25 de novo and 26 relapsed or persistent, were investigated. While only 6 out of 25 de novo AML blast populations showed moderate efflux of R123 and daunorubicin, 17 out of 26 blast populations of relapsed or persistent AML had an efflux between 20% and 44% within 15 min ex vivo. This efflux could be significantly inhibited by 1 microM BIBW22, 1 microM dexniguldipine, or 10 microM verapamil. For idarubicin we found an effusion of 40+/-9% within 15 min in all blast populations that could not be inhibited by the modulators. Clinically achievable drug concentrations causing only moderate side-effects are in the range of 0.5 microM dexniguldipine and 3 microM verapamil. Up to now, BIBW22 has not been investigated clinically. Thus the potential toxicity of concentrations of 0.5-1 microM BIBW22, sufficient for an optimal efflux inhibition ex vivo, is not known yet. We conclude from our ex vivo investigations in blast populations of de novo, relapsed or persistent AML that BIBW22 is a potent modulator of MDR.

Antigens, CD34↗

PubMed1996

Effects of cyclosporin A and FK-506 on stem cell factor-induced histamine secretion and growth of human mast cells.

Stem cell factor (SCF) is a key regulator of human mast cells (MCs) and a potential mediator of allergy. In this study the effects of cyclosporin A (CSA) and FK-506, two potent immunosuppressive drugs, on SCF-dependent histamine release and growth of human MCs were analyzed. Preincubation of tissue MCs with CSA (3 micrograms/ml) resulted in inhibition of histamine release provoked by either recombinant human (rh) SCF (70.3% +/- 20.6% inhibition, p < 0.001) or anti-IgE (76.7% +/- 21.9%, p < 0.001) or by rhSCF+ anti-IgE (77.4% +/- 13.9%, p < 0.001). Almost the same inhibition was produced by FK-506 (rhSCF: 82.0% +/- 18.9% inhibition, p < 0.001; anti-IgE: 71.5% +/- 16.7%, p < 0.001; rhSCF+ anti-IgE: 70.0% +/- 7.3%, p < 0.001). The effects of CSA and FK-506 on SCF-dependent release of histamine were dose-dependent (IC50: CSA, 1 to 10 ng/ml; FK-506, 0.3 to 3 ng/ml). IC50 values about three to 10 times higher were found for MCs preincubated with rhSCF before anti-IgE activation, compared with anti-IgE or SCF alone. SCF-dependent differentiation of human MCs was analyzed in a long-term suspension culture system (n = 6). Unexpectedly, CSA and FK-506 were unable to suppress, but even enhanced SCF-dependent growth of MCs and formation of MC tryptase in long-term culture. Together, CSA and FK-506 inhibit SCF-dependent release of histamine from human MCs and even augment SCF-dependent growth of human MCs in long-term culture.

Cell Division↗

PubMed1996

Stem cell factor-induced downregulation of c-kit in human lung mast cells and HMC-1 mast cells.

Recent data suggest that local overexpression of the tissue-hormone c-kit ligand (stem cell factor [SCF]) is associated with accumulation of mast cells (MCs) and a decrease in expression of c-kit in the accumulated MCs [28]. In the present study, the effects of recombinant human (rh) SCF on expression of c-kit mRNA and c-kit protein in isolated human MCs and a human mast cell line, HMC-1, were analyzed. Incubation of isolated lung MC with rhSCF (100 ng/mL) for 120 minutes resulted in decreased expression of c-kit mRNA (optical density [OD], control: 100% vs. rhSCF: 37%). Almost identical results were obtained with HMC-1 cells (OD, control: 100% vs. rhSCF: 40 to 45%). As assessed by flow cytometry and monoclonal antibodies (mAbs) to c-kit, the SCF-induced decrease of c-kit mRNA in HMC-1 was associated with a substantial decrease in surface expression of c-kit (MFI, control: 100 +/- 21%, vs. MFI in cells incubated with rhSCF [100 ng/mL at 37 degrees C for 12 hours]: 8 +/- 2%, vs. MFI in cells incubated with rhSCF, 100 ng/mL, at 4 degrees C: 34 +/- 3%). The effects of rhSCF on c-kit expression in HMC-1 cells were dose- and time-dependent with maximum effects observed with 10-100 ng/mL of rhSCF after 4 to 12 hours. The SCF-dependent loss of c-kit was also accompanied by a decreased chemotactic response to rhSCF (control: 100%; rhSCF: 71 +/- 2%). This study shows that exposure of human lung MC and HMC-1 cells to recombinant SCF results in downregulation of c-kit mRNA and surface c-kit expression. These data may explain the partial loss of c-kit on MCs in areas of SCF overexpression.

Blotting, Northern↗

PubMed1995

Differential expression of complement receptors on human basophils and mast cells. Evidence for mast cell heterogeneity and CD88/C5aR expression on skin mast cells.

Complement-dependent activation of immune cells is regulated by cell surface membrane receptors. In this study, expression of complement receptors (CR) on human blood basophils (n = 11), tissue mast cells (lung, n = 7; skin, n = 10; uterus, n = 4; tonsil, n = 3; heart, n = 10), and on respective human cell lines (basophil line KU-812, mast cell line HMC-1) was analyzed by the use of mAbs and indirect immunofluorescence. Normal blood basophils and KU-812 cells were found to express C5aR (CD88), membrane cofactor protein (CD46), decay-accelerating factor (CD55), and membrane attack complex inhibitory factor (CD59), as well as the previously recognized CR1 (CD35), CR3 alpha (CD11b), CR4 alpha (CD11c), and CR3/4 beta (CD18). Mast cells from all organs as well as HMC-1 cells expressed CD46, CD55, and CD59, but not CD11b, CD21, or CD35. The C5aR (CD88) was detectable on skin mast cells, a subset (5 to 15%) of cardiac mast cells, and on HMC-1 cells, but not on lung, uterus, or tonsillar mast cells (< 5%). Moreover, double immunoperoxidase staining (tryptase vs C5aR/CD88) revealed in situ expression of C5aR on skin, but not lung mast cells. Recombinant human (rh) C5a, at 10(-10) to 10(-7) M, induced secretion of histamine from basophils (rhC5a, 10(-8) M: 53.4 +/- 3.1% vs control < 5%) and from skin mast cells (rhC5a, 10(-8) M: 25.8 +/- 16.1% vs control < 10% histamine release), but not from other mast cells (rhC5a or control: < 10%, p > 0.05). The rhC5a-induced secretion of histamine from basophils and skin mast cells was inhibited by S5/1, a blocking Ab against CD88 (basophils: 37.2% to 75.1%; skin mast cells: 39.2% to 83.9% inhibition, p < 0.05). Together, this study shows that a) basophils and mast cells express a different profile of complement receptors, b) C5a-dependent mediator release in skin mast cells and basophils is mediated via CD88, and c) mast cells constitute a heterogeneous lineage in terms of expression of the C5a binding site CD88.

Antigens, CD↗

PubMed1995

Differential response of human basophils and mast cells to recombinant chemokines.

Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 micrograms/ml: 26.9 +/- 3.4%; other chemokines: < 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (< 1 microgram/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n = 2), skin (n = 1), uterus (n = 3), or tonsils (n = 3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2R beta, CD63, IL-3R alpha, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.

Antigens, CD↗

PubMed1995

Influence of hematocrit and platelet count on impedance and reactivity of whole blood for electrical aggregometry.

Previous studies have shown that differing qualities of blood specimen seem to influence whole blood electrical aggregometry (WBEA), making it difficult to standardize the method. The aim of this study was to investigate the impact of hematocrit (HCT) and platelet count (PLC) on in vitro platelet aggregation in citrated whole blood (CWB) in order to compensate for their possible effects on impedance aggregometry. Red blood cells and blood platelets were isolated from fresh citrated whole blood taken from 15 healthy donors (mean age = 26 years) and recombined to 20 physiologically relevant combinations of hematocrit and platelet count (HCT: 20-50, PLC: 100-500). Platelet aggregability was measured using WBEA with three different triggers. A special-purpose software package was used in this study, ensuring proper calibration, acquisition, and evaluation of analogue to digital converted data, allowing the calculation of a set of characteristic parameters of each impedance curve. Most of the linear regressions showed that all parameters significantly depend on HCT and PLC. Furthermore, we found interactions of both variables, making it impossible to focus on the effects of one of the investigated variables only. The outcome of this study is a set of dependences, allowing the calculation of regressions for in vitro aggregation in whole blood, enabling a comparison of blood of any quality with each other, regardless of the variables HCT and PLC. Together with the previously defined dependence of sample age on WBEA data, this step should help to make this technique a more reliable and practicable clinical tool, making it suitable for daily routine investigations.

Adult↗

PubMed1995

[Diagnostic and therapeutic video thoracoscopy: conversion rate and costs].

With the further development of new surgical techniques, that allow for the performance of a variety of standard diagnostic and therapeutic procedures in a less invasive fashion, it is instructive to look at the complications of these new techniques, in order to define their role for general thoracic surgery. 372 patients have been treated by means of video-assisted thoracic surgery (VATS) between 1/1992 and 12/1994. A total of 934 open thoracic procedures were performed in the same time frame, 399 out of them for the same chest disorders as treated by VATS alternatively. In 40 cases (10.7%) the endoscopic procedure had to be converted to an open thoracotomy. The main reasons for conversion were inability to locate or resect lesions due to a deep or central position (n = 13), requirement of further resection (n = 10), adhesions (n = 9), fibrinopurulent empyema (n = 5), bleeding (n = 2) and single-lung-ventilation failure (n = 1). The mean operation time was significantly shorter with VATS compared to open procedures, except for decortications. The mean hospital stay was 4.2 days in the endoscopic and 7.9 days in the thoracotomy group. Cost analysis for both techniques included expenses for disposable instruments, the operation room, anesthesia, and total hospital charges. Higher costs for instruments for VATS procedures were compensated by shorter chest drainage, less postoperative need for analgetics and a significantly shorter hospital stay.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗

PubMed1994

Capacity of individual chronic lymphatic leukemia lymphocytes and leukemic blast cells for repair of O6-ethylguanine in DNA: relation to chemosensitivity in vitro and treatment outcome.

The elimination kinetics of the alkylation product O6-ethylguanine (O6eGua) from nuclear DNA were determined in individual lymphocytes or blast cells isolated from 27 patients with chronic lymphatic leukemia (CLL) and 26 patients with de novo acute myeloid leukemia (AML). A monoclonal antibody-based immunocytological assay was used for quantification of O6eGua in DNA of individual cells after pulse exposure of cells to N-ethyl-N-nitrosourea (EtNU). In cell specimens from a given patient, no major subpopulations with significantly different capacities for repair of O6eGua were observed. The time required to remove 50% of induced O6eGua residues varied interindividually between 0.5 and 8.4 h in CLL lymphocytes and between 0.8 and 6.3 h in leukemic blast cells. An inverse relationship was found between the rate of removal of O6eGua from DNA and the chemosensitivity of cells to EtNU, 1,3-bis(2-chloroethyl)-1-nitrosourea or mafosfamide in vitro. High rates of O6eGua repair and pronounced resistance to mafosfamide, 1,3-bis(2-chloroethyl)-1-nitrosourea, and EtNU in vitro were found in samples from 8 CLL patients nonresponsive to chemotherapy with alkylating agents. In AML patients treated with anthracyclines and 1-beta-D-arabinofuranosylcytosine, no relation was found between DNA repair capacity and treatment outcome. However, increased P-glycoprotein expression was observed between specimens derived from AML patients who had failed to reach complete remission (n = 12) after chemotherapy versus responsive patients (n = 14). DNA repair rate was not related to chemosensitivity to Adriamycin and 1-beta-D-arabinofuranosylcytosine in vitro, nor were cellular glutathione content, glutathione S-transferases activity, or P-glycoprotein expression.

Acute Disease↗

PubMed1994

Improved flow-cytometric detection of low P-glycoprotein expression in leukaemic blasts by histogram subtraction analysis.

Expression of the drug efflux pump P-glycoprotein (PGP) was determined by flow cytometry in human lung cancer cell lines and in leukaemic blasts derived from 60 patients with acute myeloid leukaemia (AML). Cells from the PGP-negative parent cell line H69/P and the multidrug resistant (MDR)-variant H69/LX4 could be clearly distinguished by immunostaining with the anti-PGP monoclonal antibody MRK16. In leukaemic blasts, the differences in fluorescence intensities between samples incubated with the idiotypic nonspecific (control sample) and specific antibody (test sample) were small, resulting in nondisjunct distributions. Only in a few leukaemia specimens were PGP-expressing cells detectable by simple subtraction of histograms using a threshold. Therefore, an improved histogram subtraction analysis, based on curve fitting and a statistical test, was applied to distinguish antigen-positive from antigen-negative cells. Moreover, a multiparametric staining procedure employing propidium iodide (PI) and Hoechst 33342 was used to reduce staining artefacts. By this approach, leukaemic cells with low expression of PGP were detected in 39 out of 60 cases. Subpopulations with strong PGP expression, resulting in disjunct fluorescence distributions, were not observed. Only in 5 out of 60 specimens were PGP expressing cells detected by a conventional subtraction of histograms using a threshold. Comparison of data obtained with or without the multiparametric gating procedure indicated that the increase in sensitivity was mainly due to the application of the data analysis. However, exclusion of cell debris using PI and Hoechst staining properties reduced the deviation of data from mean values. No relation between PGP expression and cell cycle position was observed in either cell lines or in leukaemic blasts.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Repair of O6-alkylguanines in the nuclear DNA of human lymphocytes and leukaemic cells: analysis at the single-cell level.

Inter-individual and cell-cell variability of repair of O6-alkylguanines (O6-AlkGua) in nuclear DNA was studied at the single-cell level in peripheral lymphocytes from healthy donors and in leukaemic cells isolated from patients with chronic lymphatic leukaemia (CLL) or acute myeloid leukaemia (AML). Cells were pulse exposed to N-ethyl- or N-(n-)butyl-N-nitrosourea in vitro, and O6-AlkGua residues in DNA were quantified using an anti-(O6-AlkGua) monoclonal antibody and electronically intensified fluorescence. The kinetics of O6-AlkGua elimination revealed considerable inter-individual differences in O6-ethylguanine (O6-EtGua) half-life (t1/2) values in DNA, ranging from 1.5 to 4.5 h (five AML patients), from 0.8 to 2.8 h (five CLL patients) and from 1.2 to 7.3 h (five healthy donors). The elimination from DNA of equimolar amounts of O6-butylguanine was generally 3-5 times slower in comparison with O6-EtGua. The t1/2 values of individual samples varied in parallel for both DNA alkylation products. Upon preincubation with O6-benzylguanine, the activity of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AT) in both lymphocytes and leukaemic blasts was reduced to < or = 1%. However, while the rate of O6-EtGua elimination from DNA was decelerated it was not abolished, suggesting the possible involvement of additional repair systems that might be co-regulated with AT. Within individual samples, no major cell subpopulations were observed whose repair kinetics would differ significantly from the remaining cells.

Alkylating Agents↗

PubMed1994

The branching angles in computer-generated optimized models of arterial trees.

The structure of a complex arterial tree model is generated on the computer using the newly developed method of "constrained constructive optimization." The model tree is grown step by step, at each stage of development fulfilling invariant boundary conditions for pressures and flows. The development of structure is governed by adopting minimum volume inside the vessels as target function. The resulting model tree is analyzed regarding the relations between branching angles and segment radii. Results show good agreement with morphometric measurements on corrosion casts of human coronary arteries reported in the literature.

Animals↗

PubMed1994

The Vienna implantable centrifugal blood pump.

Because of the inherent disadvantages of membrane pumps, rotary pumps have been increasingly investigated in recent years. As a result of improving biocompatibility, extended assistance with implantable devices is of special interest. Questions arise concerning shear stress, blood traumatization, design of seals, and specific control conditions. In their development of an implantable impeller pump, the Vienna group studied the minimization of hemolysis and thrombus formation by means of numerical simulation, visualization, and in vitro blood evaluation. The latter was revealed to be the most powerful tool for pump evaluation. With optimization of geometry, a hemolysis of in vitro: IH = 0.008; MIH = 0.58; and in vivo: 2.1 to 3 mg% plasma-free hemoglobin could be obtained. For proper control and physiological adaptation, a controller based on a nonlinear and a fuzzy strategy was developed. Furthermore, a method for evaluation of the contractility of the assisted heart during nonpulsatile support was tested by computer simulation. This paper summarizes the evaluation methods used and provide an overview of the results of pump and controller design.

Animals↗

PubMed1993

[Isolated amyloidosis of hilar lymph nodes].

Pseudotumoral mediastinal and pulmonary amyloidosis occur infrequently and may be confused with other tumors that are found more commonly in this region. Enlargement of hilar lymph nodes in the absence of pulmonary involvement is extremely rare. We report a case of nodular amyloidosis of the hilar lymph nodes that was studied using different diagnostic and radiologic methods. A previously healthy 79-year-old man presented with a large right hilar mass detected on routine chest roentgenography. The extensive mass behaved like a solid tumor and mimicked a bronchogenic carcinoma. At thoracotomy, frozen sections revealed the tumor to consist of kappa-light-chain amyloid. In light of the irresectibility of the tumor, thoracotomy was ended as open biopsy. Immunoelectrophoretic analyses of the plasma and urine showed no evidence of a paraprotein immunoglobulin or light chains. The patient was discharged without symptoms of disease. Different diagnostic procedures before and after surgery are discussed.

Aged↗

PubMed1993

Mechanical blood traumatization by tubing and throttles in in vitro pump tests: experimental results and implications for hemolysis theory.

Blood has become essential as a test fluid to evaluate hemolysis and biocompatibility of blood pumps in vitro. The blood is usually pumped from a blood bag into a circuit against elevated pressure. A throttle or a length of tubing is used to produce the pressure head. Blood damage caused by the shear stress in these pressure-reducing devices should be minimal. It is not known whether the high but short-lasting shear stress in a throttle is more or less damaging to the blood than the low but long-lasting stress in tubing. In this study, throttles (width 11 mm, minimal height 0.9 mm, length 30 mm; shear stress = 136 N/m2 lasting for 3.23 ms); and tubing (inner diameter 9.5 mm, length 4.5 m, shear stress = 4.5 N/m2 lasting for 3.5 s) were compared at a flow of 5 L/min and a pressure drop of 150 mm Hg. Experiments (n = 10) with bovine blood were performed in two parallel setups using Bio-Medicus pumps BP80. Free hemoglobin in plasma (fHb) and thromboxane B2 (TXB2) were measured. After 6 h, the fHb increase was 31.9 +/- 19.1 mg% for the throttle setup and 32.3 +/- 16.2 for the tubing setup. The TXB2 release was 296 +/- 70 and 305 +/- 54 pg/0.1 ml respectively after 4 h. In summary, no significant differences between the two setups for either fHb or TXB2 could be detected. So the use of a throttle, which requires far less priming volume and a smaller blood-contacting surface while also offering a wider range of adjustment, seems preferable.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

In vitro investigation of thrombogenesis in rotary blood pumps.

Thrombus formation at sealing and stagnation areas remains a major problem in the development of rotary blood pumps. Until now, the complex phenomena could only be studied in vivo. In this study, an in vitro mock circulation previously used for hemolysis studies was adapted for thrombosis evaluation. Blood was collected in the slaughterhouse with strict avoidance of air contact and was heparinized (1.5 U heparin/ml blood; activated coagulation time [ACT]: initially, 140-180 s; after collection, 400-600 s). During the test, the ACT decreased gradually. The tests were stopped after 90 to 180 min at an ACT of 1.5 times the initial value. Thrombus formation was observed at the same locations as observed in left-heart assist devices (sealing area, connecting bolts, and stagnant water areas at connectors). The thrombi were similar in shape, color, and histology to those found after 2 to 4 days in vivo. This test provides a valuable tool for evaluating thrombus formation in prototypes and screening tests of different rotary pump designs.

Animals↗