van Willem Oeveren

Phosphorylcholine coating of extracorporeal circuits provides natural protection against blood activation by the material surface

OBJECTIVE The aim of this study is to evaluate the use of a new coating, mimicking the outer cell membrane, in paediatric cardiac surgery. METHODS Two groups of ten patients with a body weight below 8 kg, undergoing elective cardiac operations for different congenital anomalies, were prospectively enrolled in this study. In one group the whole extracorporeal circuit, including the cannulas, was coated with phosphorylcholine (PC). In the second group the same circuit was used without coating. Platelet activation (thromboxane B2 (TXB2), beta-thromboglobulin (betaTG)), activation of the coagulation system (F1+2), leukocyte activation (CD11b/CD18) and terminal complement activation (TCC) were analyzed pre-cardiopulmonary bypass (CPB), at 15, 60 min of CPB, at the end of CPB, 20 min post CPB and at postoperative day 1 and 6. RESULTS No statistical differences were found for F1+2 and CD11b/CD18. After onset of CPB mean levels of TCC remained stable in the PC group whereas an increase was observed in the control group. During CPB betaTG values in both groups increased to a maximum at the end of CPB. Within groups the increase in betaTG levels during CPB was statistically significant (P<0.05) from baseline in the control group starting from 60 min of CPB whereas no statistical difference was observed in the PC group. After the start of CPB TXB2 mean levels increased to 405+/-249 pg/ml in the PC group vs. 535+/-224 pg/ml in the control group. After this initial increase there was a small decline in the PC group with further increase. This was in contrast to the control group were TXB2 levels further increased up to a mean of 718+/-333 pg/ml at the end of CPB (P=0.016). CONCLUSIONS Phosphorylcholine coating had a favourable effect on blood platelets, which is most obvious after studying the changes during cardiopulmonary bypass. A steady increase of TXB2 and betaTG was observed in the control group, whereas plateau formation was observed in the phosphorylcholine group. Clinically, this effect may contribute to reduced blood loss and less thromboembolic complications. Complement activation is lower in the coated group.

On the influence of flow conditions and wettability on blood material interactions

In this review, we hypothesise that, next to biocompatibility, optimal blood compatibility depends on a combination of biomaterials wettability and the shear stress prevailing in the device. The wettability is discussed in seven different categories of devices, that differ substantially from each other with regard to shear stress and exposure time. These seven categories are stents, prosthetic heart valves, vascular prostheses, cardiopulmonary bypass, hemodialysis, vena cava filters and blood bags. In high shear applications, in combination with blood activation, platelet deposition and thrombosis appear to be major problems and platelet inhibitors are most effective. Exposure of blood to a large biomaterial surface, with or without antithrombotic coating, results in reduction of platelet function. Material-independent activation aggravates this process. In low shear applications, platelets only seem supportive for coagulation and anticoagulants should be used.

Leucocyte depletion during cardiac surgery: a comparison of different filtration strategies

The results of leucocyte filtration during cardiac surgery are conflicting. This may be due to timing and duration of the filtration procedure, and to flow and pressure conditions in the filter. Therefore, we prospectively compared three major leucocyte filtration strategies in cardiac surgical patients. Forty patients were randomly divided into four groups. Group I: leucofiltration of arterial blood throughout cardiopulmonary bypass (CPB) (associated with high-flow and pressure gradients), Group II: leucofiltration of a part of the venous return blood in the re-warming phase during CPB (associated with intermediate flow, but high pressure), Group III: leucofiltration of residual heart-lung machine blood during transfusion into the patient after CPB (associated with low flow and low pressure), Group IV: control group without leucofiltration. We measured circulating leucocyte counts, plasma elastase levels and arterial blood oxygenation. Filters were postoperatively examined using scanning electronmicroscopy (SEM). Leucocyte counts increased over time and oxygenation decreased in all groups, without significant differences between the groups. SEM demonstrated extensive protein deposits and damaged leucocytes in the deeper layers of the filters from Group I. This was not observed in the filters from Group III. The postoperative plasma elastase levels increased in Groups II and IV and decreased in Groups I and III. In conclusion, we could not demonstrate a clinical difference among the three leucocyte depletion strategies. However, our laboratory results suggest that leucocyte filtration at low flow and pressure conditions is associated with less leucocyte damage and less release of elastase.

Adhesion of blood platelets under flow to wettability gradient polyethylene surfaces made in a shielded gas plasma

Adhesion and activation of platelets are important steps in the thrombosis of blood after contact with a biomaterial surface and are governed, in part, by the wettability of the surface. Since most implanted devices are in contact with blood under flow conditions, it is important to study the effect of wettability of device surfaces on the behavior of platelets also under flow. To this end, wettability gradient polyethylene surfaces were prepared through glow discharge with partial shielding over a length of 5 cm, with advancing water contact angles varying from 95 to 45 degrees and a contact angle hysteresis of 30 degrees. The role of blood flow on the adhesion of platelets was examined by incubating these gradient surfaces in anticoagulated, whole human blood under static conditions or in blood under a flow of 10 or 40 ml/min through a 3 mm diameter circuit or for 5 or 15 min with either the hydrophobic or hydrophilic end upstream. Generally, more platelets adhered on the hydrophilic end of the wettability gradient than on the hydrophobic end, although the increment along the wettability gradient was dependent on both the flow conditions and direction. More platelets adhered under a flow of 10 ml/min than under static conditions, due to higher mass transport. Especially when the hydrophilic end was upstream, there was a more pronounced adhesion. This can be explained in terms of immediate platelet activation by shear stress imposed at the upstream end. During flow of 40 ml/min, platelet adhesion on an upstream hydrophilic end was less than on a downstream hydrophilic end. We conclude that platelets detach from the hydrophilic end at high shear stress due to the spherical form of adhered platelets. Platelets on the hydrophobic end could withstand detachment by strong, flat shaped platelet-material contact.

Induction and detection of disturbed homeostasis in cardiopulmonary bypass

During cardiopulmonary bypass (CPB) haemodynamic alterations, haemostasis and the inflammatory response are the main causes of homeostatic disruption. Even with CPB procedures of short duration, the homeostasis of a patient is disrupted and, in many cases, requires intensive postoperative treatment to re-establish the physiological state of the patient. Although mortality is low, disruption of homeostasis may contribute to increased morbidity, particularly in high-risk patients. Over the past decades, considerable technical improvements in CPB equipment have been made to prevent the development of the systemic inflammatory response syndrome (SIRS). Despite all these improvements, only the inflammatory response, to some extent, has been reduced. The microcirculation is still impaired, as measured by tissue degradation products of various organs, indicating that CPB may still be considered as an unphysiological procedure. The question is, therefore, whether we can detect the pathophysiological consequences of CPB in each individual patient with valid bedside markers, and whether we can relate this to determinant factors in the CPB procedure in order to assist the perfusionist in improving the adequacy of CPB. The use of these markers could play a pivotal role in decision making by providing an immediate feedback on the determinant quality of perfusion. Therefore, we suggest validating the proposed markers in a nomogram to optimize not only the CPB procedure, but also the patient’s safety.

Changes in glomerular filtration rate after cardiac surgery with cardiopulmonary bypass in patients with mild preoperative renal dysfunction

BACKGROUND Cardiac surgery with cardiopulmonary bypass (CPB) is commonly perceived as a risk factor for decline in renal function, especially in patients with preoperative renal dysfunction. There are few data on the effects of CPB on renal function in patients with mild preoperative renal dysfunction. The purpose of this study was to evaluate renal function in patients with pre-existing mild renal dysfunction undergoing cardiac surgery with CPB. METHODS In a multicentre study cohort we measured prospectively the glomerular filtration rate (GFR) by radioactive markers both before operation and on the 7th postoperative day in cardiac surgical patients with preoperative serum creatinine >120 micromol l(-1) (n=56). In a subgroup of patients (n=14) in addition to the GFR, the effective renal plasma flow (ERPF) and the filtration fraction (FF) were measured. RESULTS While preoperative GFR [77.9 (25.5) ml min(-1)] increased to 84.4 (23.7) ml min(-1) (P=0.005) 1 week after surgery, ERPF did not change [295.8 (75.2) ml min(-1) and 295.9 (75.9) ml min(-1), respectively; P=0.8]. In accordance, the FF increased from 0.27 (0.05) (before operation) to 0.30 (0.04) (Day 7, P=0.01). CONCLUSION Our results oppose the view that cardiac surgery with CPB adversely affects renal function in patients with preoperative mild renal dysfunction and an uncomplicated clinical course.

The influence of body mass index on the accumulation of advanced glycation end products in hemodialysis patients.

Background/Objectives:The level of skin autofluorescence (AF) at a given moment is an independent predictor of mortality in hemodialysis (HD) patients. Skin AF is a measure of the accumulation of advanced glycation end products (AGEs). The aim of the study was to estimate the influence of nutrition on the 1-year increase of skin AF (ΔAF) in HD patients.Subjects/Methods:A total of 156 HD patients were enrolled in this study. Skin AF, body mass index (BMI), superoxide dismutase, myeloperoxidase, C-reactive protein, inter-cellular adhesion molecule-1, von Willebrand factor and heart-type fatty acid-binding protein were measured four times at intervals of approximately half a year. Data from the monthly routine blood analysis were also used. Daily calorie, protein and AGE intakes were assessed from food recordings over a period of 1 week.Results:A J-shaped relation was found between baseline BMI and ΔAF (P=0.01). The lowest point of the J-shaped curve is found for BMI=24.3 kg/m2. In the univariate analysis of the contributors to the 1-year ΔAF, we found that beside BMI=24.3 kg/m2, AGE and calorie intakes, as well as myeloperoxidase and HD vintage, had a P <0.10. The sole independent predictor of the 1-year ΔAF was BMI=24.3 kg/m2 (P=0.01).Conclusions:It appears that calorie, protein and AGE intakes hardly influence the 1-year ΔAF in HD patients. BMI of HD patients of around 24 kg/m2 resulted in a lower 1-year ΔAF.

Multilink stent promotes less platelet and leukocyte adhesion than a traditional stainless steel stent: an in vitro experimental study.

Background Platelet and leukocyte deposition onto metallic struts can be a crucial factor in the outcome of a coronary stenting procedure. By means of an in vitro, closed-loop circulation model, we aimed to assess blood-stent interaction patterns for a new stainless steel stent (MultiLink, Guidant Nederland BV, Nieuwegein, the Netherlands). Methods The effect of MultiLink (n=20) on blood cells and blood activation was studied by biochemical assays. Platelet and leukocyte adhesion to MultiLink were studied by immunofluorocytometric assays (anti-GpIIIa [CD 61] and anti-CD11b labeled antibodies, respectively), and by scanning electron microscopy. MultiLink was compared with empty circuits (n=20) and to the Palmaz Schatz stent (n=20). Experiments were performed both in the presence and in the absence of an antiplatelet agent (15 μg/mL of indomethacin). Results No significant effect on blood cells and blood activation was demonstrated for MultiLink. Antiplatelet treatment significantly reduced platelet adhesion to MultiLink (from 3.78±1.28 to 2.23±0.57x106 count per second [cps]/stent) but not to the Palmaz Schatz stent (from 4.11±0.31 to 5.02±1.29x106 cps/stent)(P=0.011). Leukocyte adhesion to MultiLink was significantly less than adhesion to the Palmaz Schatz stent (7.95±1.59 vs. 9.16±1.36x106 cps/stent, respectively; P=0.016), regardless of the presence of antiplatelet treatment. Conclusions When compared with a traditional stainless steel stent, MultiLink seems to have features of improved hemocompatibility, and single antiplatelet treatment is proposed as the treatment of choice to prevent platelet deposition.

Novel polyurethanes with interconnected porous structure induce in vivo tissue remodeling and accompanied vascularization

Tissue engineering and regenerative medicine have furnished a vast range of modalities to treat either damaged tissue or loss of soft tissue or its function. In most approaches, a temporary porous scaffold is required to support tissue regeneration. The scaffold should be designed such that the turnover synchronizes with tissue remodeling and regeneration at the implant site. Segmented polyester urethanes (PUs) used in this study were based on epsilon-caprolactone (CL) and co-monomers D,L-lactide (D,L-L) and gamma-butyrolactone (BL), and 1,4-butanediisocyanate (BDI). In vitro, the PUs were nontoxic and haemocompatible. To test in vivo biocompatibility, the PUs were further processed into porous structures and subcutaneously implanted in rats for a period up to 21 days. Tissue remodeling and scaffold turnover was associated with a mild tissue response. The tissue response was characterized by extensive vascularization through the interconnected pores, with low numbers of macrophages on the edges and stroma formation inside the pores of the implants. The tissue ingrowth appeared to be related to the extent of microphase separation of the PUs and foam morphology. By day 21, all of the PU implants were highly vascularized, confirming the pores were interconnected. Degradation of P(CL/D,L-L)-PU was observed at this time, whereas the other two PU types remained intact. The robust method reported here of manufacturing and processing, good mechanical properties, and in vivo tissue response of the porous P(CL/D,L-L)-PU and PBCL-PU makes them excellent candidates as biomaterials with an application for soft tissue remodeling, for example, for cardiovascular regeneration.

Time-related contact angle measurements with human plasma on biomaterial surfaces

Axisymmetric drop shape analysis by profile (ADSA-P) was used to assess in time contact angle changes of human plasma drops placed on four different biomaterials. Results were related with conventional blood compatibility measurements: albumin adsorption, fibrinogen adsorption and platelet adhesion. While contact angle measurements with water are material-related but constant in time, contact angle measurements with plasma changed over time owing to protein adsorption on the solid-liquid interface. The contact medium plasma did not influence the initial contact angle. Contact angles on PDMS decreased most in time (41 degrees) and demonstrated highest levels of conventionally measured albumin and fibrinogen adsorption and platelet adhesion. PTFE, with the lowest contact angle decrease over a 500 minutes period (19 degrees), showed low fibrinogen and albumin adsorption as well as low platelet adhesion. PU and HDPE demonstrated almost similar initial contact angles with plasma and contact angle decreases (26 and 27 degrees), intermediate protein adsorption, and platelet adhesion. We conclude that biocompatibility properties of the tested materials may be more related to the behaviour of their contact angles in time, than to the initial hydrophobic or hydrophilic state.