Comparison of three oxygenator-coated and one total-circuit-coated extracorporeal devices

Perfusion ◽  
1999 ◽  
Vol 14 (2) ◽  
pp. 119-127 ◽  
Author(s):  
S T Baksaas ◽  
V Videm ◽  
T Pedersen ◽  
H Karlsen ◽  
T E Mollnes ◽  
...  

The present study was designed to compare the biocompatibility of three cardiopulmonary bypass setups with different surface coatings, and to determine if coating of the whole circuit with one of the coatings was more beneficial than coating of the oxygenator only. Extracorporeal devices entirely coated with synthetic polymers (Avecor, n = 6) were compared to oxygenators coated with synthetic polymers (Avecor, n = 6), end-point, covalently attached heparin (CBAS, n = 6) or absorbed heparin (Duraflo 2, n = 6) in an in vitro model of a heart-lung machine. The circuits were primed with fresh human whole blood and Ringer’s acetate and recirculated at 4 l/min at 30°C for 2 h. Test samples were obtained at regular intervals and analysed for myeloperoxidase (MPO), platelet counts, β-thromboglobulin, heparin, prothrombin fragment 1+2, plasmin-anti-plasmin complexes, and complement activation products. The mean MPO concentrations increased in the Avecor-coated oxygenator group (AV) from 247 at the start to 671 μg/l at the termination of the experiments, in the Avecor-coated total circuit group (AV-T) from 116 to 288 μg/l, in the Duraflo 2 coated oxygenator group (DU) from 160 to 332 μg/l, and in the CBAS-coated oxygenator (CA) group from 172 to 311 μg/l. The MPO concentrations increased significantly in all groups ( p < 0.03). The increase in group A was significantly higher than in the other three groups ( p = 0.007). The mean platelet counts decreased in the Avecor-coated total circuit group from 117 at start to 99 × 109/l at termination of the experiments, in the Avecor-coated oxygenator group from 119 to 103 × 109/l, in the Duraflo 2 group from 96 to 86 × 109/l, and in the CBAS group from 132 to 123 × 109/l. The platelet counts decreased significantly in all groups ( p < 0.01), but the intergroup differences were not significant ( p = 0.15). The mean β-thromboglobulin concentrations increased in the Avecor-coated total circuit group from 193 at the start to 754 ng/ml at the termination of the experiments, in the Avecor-coated oxygenator group from 474 to 1654 ng/l, in the Duraflo 2 group from 496 to 1280 ng/l, and in the CBAS group from 418 to 747 ng/l. The β-thromboglobulin increase was significant in each group ( p < 0.01), but not between the groups ( p = 0.49). The mean heparin concentrations in the Duraflo 2 group increased from 2460 at the start to 2897 IU/l at termination of the experiments, in the CBAS group from 2468 to 2518 IU/l. In the Avecor-coated oxygenator group heparin concentrations decreased from 2010 to 1968 IU/l, and in the Avecor-coated total circuit group from 2002 to 1927 IU/l. The differences in heparin concentrations were significant between the Duraflo 2 group and the other groups ( p < 0.05). The mean prothrombin fragment 1+2 concentrations increased in the CBAS group from 0.4 at the start to 2.1 nmol/l at the end of the experiments, in the Avecor-coated oxygenator group from 0.4 to 0.6 nmol/l, in the Avecor-coated total circuit group from 0.3 to 0.4 nmol/l, and in the Duraflo 2 group from 1.2 to 1.3 nmol/l. The prothrombin fragment 1+2 increase was significant in all groups ( p < 0.05), but there were no significant intergroup differences ( p = 0.54). There were no significant differences at the termination of the experiments among the four groups regarding complement activation as measured by C3 activation products and the terminal complement complex. In the present in vitro model of a heart-lung machine, none of the three specific setups with different coatings was superior with regard to all test parameters. The CBAS group generated the highest levels of prothrombin fragment 1+2 formation, but least complement activation. The increasing plasma heparin concentrations in the Duraflo 2 group indicated more unstable heparin bonding. The Avecor-coated total circuit group were superior to the Avecor-coated oxygenator group regarding plasma concentrations of MPO, but not compared to the CBAS and Duraflo 2-coated oxygenator groups.

Perfusion ◽  
1999 ◽  
Vol 14 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Svein T Baksaas ◽  
Vibeke Videm ◽  
Erik Fosse ◽  
Harald Karlsen ◽  
Thore Pedersen ◽  
...  

Cardiopulmonary bypass (CPB) exposes blood to large, foreign surfaces. This exposure may activate the cellular and humoral inflammatory systems, resulting in inflammatory reactions and organ dysfunction. Coating the inner surfaces of the bypass circuit may help alleviate these side-effects. The objective of this study was to determine the influence of two new surface treatments on blood cell and complement activation. Oxygenator and tubing sets coated with synthetic polymers ( n = 7) or heparin ( n = 7) were compared to uncoated sets ( n = 7) in an in vitro model of CPB. The circuits were run at 4 l/min and recirculated for 120 min. The inflammatory response was assessed at regular intervals by platelet counts, and activation of complement, leucocytes and platelets. We found that the median platelet counts decreased from 127 to 122 × 109/l (not significant, NS) in the synthetic polymer sets, from 96 to 88 × 109/l (NS) in the heparin-coated sets, and from 93 to 54 × 109/l ( p < 0.01) in the uncoated sets after 2 h of recirculation. There were significant differences in platelet counts between the coated sets and the uncoated set at end of experiments ( p < 0.05). Beta-thromboglobulin (BTG) concentrations increased in the synthetic polymer sets from 166 to 352 ng/ml ( p < 0.01), in the heparin coated sets from 336 to 1168 ng/ml ( p < 0.01), and in the uncoated sets from 301 to 3149 ng/ml ( p < 0.01) after 2 h of recirculation. The differences in BTG at termination of the experiments were significant among all three sets ( p < 0.05). Myeloperoxidase (MPO) concentrations in the synthetic polymer sets increased from 63 to 86 μg/l ( p < 0.01), in the heparin-coated sets from 90 to 208 μg/l ( p < 0.01), and in the uncoated sets from 122 to 513 μg/l ( p < 0.01) after 2 h of recirculation. The differences in MPO at termination of the experiments were significant among all three groups ( p < 0.01). There were no significant differences at termination of the experiments among the three sets regarding complement activation as measured by C3 activation products and the terminal complement complex. We conclude that in the current in vitro model of a CPB circuit, the synthetic polymer coating and the heparin coating caused significantly less platelet loss and granulocyte and platelet activation than the uncoated surface ( p < 0.05). The synthetic polymer coating caused significantly less granulocyte and platelet activation than the heparin coating ( p < 0.05). There was moderate complement activation within each group, but no significant differences among the three groups.


Perfusion ◽  
1987 ◽  
Vol 2 (4) ◽  
pp. 277-281
Author(s):  
G. Noera ◽  
C. Massini ◽  
G. Baggio

The use of calcium antagonists such as nifedipine for myocardial protection during cardiac surgery has been advocated by several authors. During extracorporeal circulation many factors, such as light, interaction with circuit materials and haematocrit, may contribute to decrease plasma clearance of calcium antagonists In an in vitro model of a heart-lung machine, plasma nifedipine and prime concentrations were detected with a series of samples at different temperatures (25 °C and 37 °C), haematocrits (0%, 20%, 30% and 40%) and light conditions (light and dark). The results show a rapid drop of nifedipine concentration with a halflife of about 3-9 minutes and this situation is influenced with statistical significance by the presence of light and increased haematocrit. The knowledge of this condition is useful when nifedipine is used before/ during cardiopulmonary bypass and during cardioplegia and reperfusion infusion with the use of extracorporeal devices.


Blood ◽  
2012 ◽  
Vol 119 (25) ◽  
pp. 6043-6051 ◽  
Author(s):  
Michelle Elvington ◽  
Yuxiang Huang ◽  
B. Paul Morgan ◽  
Fei Qiao ◽  
Nico van Rooijen ◽  
...  

Abstract Complement inhibitors expressed on tumor cells provide an evasion mechanism against mAb therapy and may modulate the development of an acquired antitumor immune response. Here we investigate a strategy to amplify mAb-targeted complement activation on a tumor cell, independent of a requirement to target and block complement inhibitor expression or function, which is difficult to achieve in vivo. We constructed a murine fusion protein, CR2Fc, and demonstrated that the protein targets to C3 activation products deposited on a tumor cell by a specific mAb, and amplifies mAb-dependent complement activation and tumor cell lysis in vitro. In syngeneic models of metastatic lymphoma (EL4) and melanoma (B16), CR2Fc significantly enhanced the outcome of mAb therapy. Subsequent studies using the EL4 model with various genetically modified mice and macrophage-depleted mice revealed that CR2Fc enhanced the therapeutic effect of mAb therapy via both macrophage-dependent FcγR-mediated antibody-dependent cellular cytotoxicity, and by direct complement-mediated lysis. Complement activation products can also modulate adaptive immunity, but we found no evidence that either mAb or CR2Fc treatment had any effect on an antitumor humoral or cellular immune response. CR2Fc represents a potential adjuvant treatment to increase the effectiveness of mAb therapy of cancer.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1091-1091
Author(s):  
Jorell Gantioqui ◽  
Ivan Stevic ◽  
Paul Y. Kim ◽  
Keith K. Lau ◽  
Anthony K.C. Chan ◽  
...  

Abstract Abstract 1091 Background: In the presence of thrombocytopenia, antithrombotic therapy in patients with thrombosis is a challenge for the managing physicians. Current guidelines are based on anecdotal data and expert opinion. Hereby, we used an in-vitro model with thrombelastography (TEG) to study the interactions of anticoagulants with plasma clotting proteins and varying concentrations of platelets. The objective of this study is to better elucidate the range of platelet concentrations in plasma which will permit clot formation in the presence of anticoagulant. Methods: Fresh human platelet-rich plasma and platelet-poor plasma were obtained from the same donors to produce plasma samples with predefined platelet counts. For each experiment, these samples were incubated with a reaction mixture containing 30 μg/mL corn trypsin inhibitor and one of the following anticoagulants at therapeutic concentrations: heparin (0.3 IU/mL), dalteparin (1.0 IU/mL), fondaparinux (1.25 mg/L), rivaroxaban (150 ng/mL) or dabigatran (180 ng/mL). Clotting was initiated with 10 mM CaCl2 and tissue factor (TF) (Thromborel® S). The amount of tissue factor for each anticoagulant was pre-optimized so that the plasma did not clot in the absence of platelets but the clotting time would return to baseline when platelet count increased to 150 x109/L, corresponding to the expected clinical profile. All parameters for TEG (R,a, MA, TMA) were monitored for 180 min. The area under the curve for each TEG tracing in the first 15 min (AUC15) after clot initiation was estimated as it represents a global measurement of clot strength during its formation. Williams' t-test was used to compare multiple data points with its corresponding baseline control. A p < 0.05 was considered statistically significant. Results: The TF concentration in Thromborel S® was 3140 pM as determined by ELISA. We found that the optimal TF concentrations required for each anticoagulant were 1.2 pM, 0.7 pM, 0.07 pM for heparin, dalteparin, and fondaparinux respectively. No extrinsic tissue factor was required for rivaroxaban and dabigatran. In the presence of an anticoagulant, clot formation was significantly delayed when platelet counts were below 50 x109/L (fig.1). In contrast, when platelet counts were between 50–150 x109/L, there were no significant differences in all TEG parameters. The AUC15 linearly decreased when platelet counts fell below 150 x109/L. In the presence of heparinoids, the overall AUCs are reduced by an average of 6-fold comparing to the controls without anticoagulants (fig.2). In the presence of rivaroxaban or dabigatran the reduction in the overall AUCs was minimal compared to the heparinoids. The slopes of AUC15 against platelet count in the heparinoids were similar, with an average slope of 15. In contrast, the direct factor specific anticoagulants had distinctly different slopes that averaged at 56. Conclusion: Our findings suggest that, in the presence of therapeutic concentration of an anticoagulant, coagulation is delayed when platelet count is below 50 x109/L and clot formation is globally attenuated with lower platelet counts. Due to the fact that the clotting time is significantly prolonged when platelet counts fall below the threshold of 50 x109/L, we recommend withholding or reducing anticoagulants when patients with thrombocytopenia have platelet counts lower than this level. This data is consistent with the current clinical practice in adult population. Furthermore, since rivaroxaban and dabigatran required no extrinsic TF to initiate clot formation in our model, these new anticoagulants may have a wider safety margins for the treatment of thrombosis in thrombocytopenic patients. Yet, without the availability of specific antidote for these new anticoagulants, their use in patients with high bleeding risk warrants further evaluation. Disclosures: No relevant conflicts of interest to declare.


2003 ◽  
Vol 47 (10) ◽  
pp. 3145-3148 ◽  
Author(s):  
John Curtin ◽  
Martin Cormican ◽  
Gerard Fleming ◽  
John Keelehan ◽  
Emer Colleran

ABSTRACT Central venous catheter (CVC)-related infection (CVC-RI) is a common complication of CVC use. The most common etiological agents of CVC-RI are gram-positive organisms, in particular, staphylococci. An in vitro model for the formation of biofilms by Staphylococcus epidermidis ATCC 35984 on polyurethane coupons in a modified Robbins device was established. Biofilm formation was confirmed by electron microscopy and was quantified by determination of viable counts. Mueller-Hinton broth was replaced with sterile physiological saline (control) or a solution of vancomycin (10 mg/ml), gentamicin (10 mg/ml), linezolid (2 mg/ml), or eperezolid (4 mg/ml). Viable counts were performed with the coupons after exposure to antimicrobials for periods of 24, 72, 168, and 240 h. The mean viable count per coupon following establishment of the biofilm was 4.6 × 108 CFU/coupon, and that after 14 days of exposure to physiological saline was 2.5 × 107 CFU/coupon. On exposure to vancomycin (10 mg/ml), the mean counts were 2.5 × 107 CFU/coupon at 24 h, 4.3 × 106 CFU/coupon at 72 h, 1.4 × 105 CFU/coupon at 168 h, and undetectable at 240 h. With gentamicin (10 mg/ml) the mean counts were 2.7 × 107 CFU/coupon at 24 h, 3.7 × 106 CFU/coupon at 72 h, 8.4 × 106 CFU/coupon at 168 h, and 6.5 × 106 CFU/coupon at 240 h. With linezolid at 2 mg/ml the mean counts were 7.1 × 105 CFU/coupon at 24 h and not detectable at 72, 168, and 240 h. With eperezolid (4 mg/ml) no viable cells were recovered after 168 h. These data suggest that linezolid (2 mg/ml) and eperezolid (4 mg/ml) achieve eradication of S. epidermidis biofilms more rapidly than vancomycin (10 mg/ml) and gentamicin (10 mg/ml).


1999 ◽  
Vol 45 (8) ◽  
pp. 1190-1199 ◽  
Author(s):  
Philippe H Pfeifer ◽  
Marleen S Kawahara ◽  
Tony E Hugli

Abstract Background: Ongoing in vitro complement (C) activation in citrate or EDTA plasma has prevented an accurate analysis of C-activation products generated in vivo. The aim of this study was to characterize handling and storage conditions required to prevent in vitro C activation in blood and plasma samples collected with Futhan/EDTA. Methods: BiotrakTM RIAs were used to quantitatively measure C3a and C4a in blood and/or plasma samples from healthy individuals (controls) and from liver transplant patients. Blood samples were routinely drawn into either EDTA (1 g/L) tubes or into tubes containing both EDTA (1 g/L) and Futhan (0.1 g/L) and immediately centrifuged at 2000g for 15 min at 4 °C. Results: In controls, C4a, but not C3a, in fresh samples (time 0) was higher in EDTA plasma than in Futhan/EDTA plasma (n = 20; P = 0.002). Futhan/EDTA prevented C3a and C4a generation in blood and plasma samples held at room temperature (22–23 °C) for 1 h and in plasma held for 24 h at 4 °C or −70 °C. The mean C3a concentration (1.76 mg/L; n = 19) at time 0 in EDTA plasma samples from liver transplant patients was significantly higher than for controls (0.34 mg/L; n = 11). In these patients, the mean C3a in EDTA samples increased to 13.8 mg/L after 60 min at room temperature, but there was no change in the C3a concentration of an EDTA plasma from a control. In the patients, C3a concentrations were lower in Futhan/EDTA plasma than in EDTA at time 0 and after 60 min at room temperature (1.40 and 2.02 mg/L, respectively). The mean patient C4a was 4.02 mg/L in EDTA plasma at time 0 vs 0.24 mg/L for controls; it increased to 16.9 mg/L after 60 min at room temperature compared with 0.76 mg/L for controls. The mean patient C4a was 0.83 mg/L in Futhan/EDTA plasma at time 0 vs 0.1 mg/L for controls. Neither patient nor control C4a concentrations increased vs time in Futhan/EDTA. Conclusion: The combination of Futhan (0.1 g/L) and EDTA (1 g/L) eliminates in vitro C activation.


2015 ◽  
Vol 41 (5) ◽  
pp. 532-537 ◽  
Author(s):  
Souheil Hussaini ◽  
Tritala K. Vaidyanathan ◽  
Abhinav P. Wadkar ◽  
Firas A. Al Quran ◽  
David Ehrenberg ◽  
...  

An in vitro experimental model was designed and tested to determine the influence that peri-implant strain may have on the overall crestal bone. Strain gages were attached to polymethylmethacrylate (PMMA) models containing a screw-type root form implant at sites 1 mm from the resin-implant interface. Three different types of crown superstructures (cemented, 1-screw [UCLA] and 2-screw abutment types) were tested. Loading (1 Hz, 200 N load) was performed using a MTS Mechanical Test System. The strain gage data were stored and organized in a computer for statistical treatment. Strains for all abutment types did not exceed the physiological range for modeling and remodeling of cancellous bone, 200–2500 μɛ (microstrain). For approximately one-quarter of the trials, the strain values were less than 200 μɛ the zone for bone atrophy. The mean microstrain obtained was 517.7 μɛ. In conclusion, the peri-implant strain in this in vitro model did not exceed the physiologic range of bone remodeling under axial occlusal loading.


Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1023
Author(s):  
Katharina Gerling ◽  
Lisa Maria Herrmann ◽  
Christoph Salewski ◽  
Melanie Wolf ◽  
Pia Müllerbader ◽  
...  

During surgical procedures, cotton abdominal swabs with their high absorptive capacity and malleability are used to retain organs and absorb blood or other body fluids. Such properties of the natural material cotton are advantageous for most operations, but in cardiopulmonary bypass (CPB) surgery, a high blood volume can accumulate in the thoracic cavity that is quickly retransfused via the heart–lung machine (HLM). This common practice is supposed to be safe due to the high anticoagulation. However, in vitro analyses showed that blood cells and plasma proteins were activated despite a high anticoagulation, which can propagate especially an inflammatory response in the patient. Thus, we investigated patients’ blood during CPB surgery for inflammatory and coagulation-associated activation after contact to the HLM and either cotton or synthetic abdominal swabs. Contact with cotton significantly increased thrombocyte and neutrophil activation measured as β-thromboglobulin and PMN-elastase secretion, respectively, compared to synthetic abdominal swabs. Both inflammatory cytokines, interleukin (IL) 1β and IL6, were also significantly increased in the cotton over the synthetic patient group, while SDF-1α was significantly lower in the synthetic group. Our data show for the first time that cotton materials can activate platelets and leukocytes despite a high anticoagulation and that this activation is lower with synthetic materials. This additional activation due to the material on top of the activation exerted by the tissue contact that blood is exposed to during CPB surgery can propagate further reactions in patients after surgery, which poses a risk for this already vulnerable patient group.


2009 ◽  
Vol 54 (1) ◽  
pp. 397-404 ◽  
Author(s):  
Weiling Fu ◽  
Terri Forster ◽  
Oren Mayer ◽  
John J. Curtin ◽  
Susan M. Lehman ◽  
...  

ABSTRACT Microorganisms develop biofilms on indwelling medical devices and are associated with device-related infections, resulting in substantial morbidity and mortality. This study investigated the effect of pretreating hydrogel-coated catheters with Pseudomonas aeruginosa bacteriophages on biofilm formation by P. aeruginosa in an in vitro model. Hydrogel-coated catheters were exposed to a 10 log10 PFU ml−1 lysate of P. aeruginosa phage M4 for 2 h at 37°C prior to bacterial inoculation. The mean viable biofilm count on untreated catheters was 6.87 log10 CFU cm−2 after 24 h. The pretreatment of catheters with phage reduced this value to 4.03 log10 CFU cm−2 (P < 0.001). Phage treatment immediately following bacterial inoculation also reduced biofilm viable counts (4.37 log10 CFU cm−2 reduction; P < 0.001). The regrowth of biofilms on phage-treated catheters occurred between 24 and 48 h, but supplemental treatment with phage at 24 h significantly reduced biofilm regrowth (P < 0.001). Biofilm isolates resistant to phage M4 were recovered from catheters pretreated with phage. The phage susceptibility profiles of these isolates were used to guide the development of a five-phage cocktail from a larger library of P. aeruginosa phages. The pretreatment of catheters with this cocktail reduced the 48-h mean biofilm cell density by 99.9% (from 7.13 to 4.13 log10 CFU cm−2; P < 0.001), but fewer biofilm isolates were resistant to these phages. These results suggest the potential of applying phages, especially phage cocktails, to the surfaces of indwelling medical devices for mitigating biofilm formation by clinically relevant bacteria.


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