Blood Compatibility of Widely used Central Venous Catheters; an Experimental Study

Background: An inserted central venous catheter (CVC) is considered foreign material by the inert host defence systems and induce inflammation and thrombus formation. The objective of this study was to evaluate blood compatibility of six commonly used CVCs.Methods: Three coated and three uncoated CVC materials were tested in a modified Chandler loop model. Each catheter material circulated in blood from ten different healthy volunteers for 1 hour. Blood cell counts and measurements of the inert host defence systems were performed on blood samples from the loop.Results: All the tested catheters demonstrated impact on blood cells, contact coagulation, the complement system, or inflammatory markers, although the impact varied significantly.Conclusions: Of the catheters we evaluated, the most unfavourable blood compatibility profile was found for the polyurethane CVC coated with chlorohexidine and silver sulfadiazine. The greatest variation in blood compatibility between test runs was noted for the silicone dialysis catheter. Poor blood compatibility should be taken seriously but given the experimental design of the current study the clinical significance remains to be evaluated.

Differences in human and minipig platelet number, volume and activation induced by borosilicate glass beads in a modified chandler loop-system

The pig is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russel and Burchs’ 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans they are tested mostly for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of porcine and human platelets when they come into contact with glass, which was used as an exemplary thrombogenic material. For this purpose changes of platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the blood flow. Minipig and human platelets showed significant differences in number and volume, but not in activation after 4–8 min exposure to glass.

Differences in human and sheep platelet adherence, aggregation and activation induced by glass beads in a modified chandler loop-system

In human cardiovascular research, sheep in particular are used as a large animal model in addition to pigs. In these animals, medical products, developed and tested for human medical purposes, are almost exclusively used in interventional studies. Therefore, the extent to which platelets from human and ovine blood differ in terms of adherence, aggregation and activation after a 4- or 8-minutes exposure to glass was investigated. Testing was performed with platelet-rich plasma (PRP) and a modified Chandler loop system, with 4- and 8-minute blood-material exposure times corresponding to 20 and 40 test cycles, respectively, through the entire silicon tube loop of the test system. In sheep and human PRP, contact with the silicone tubing resulted in a decrease in platelet count after 4 minutes and 20 test cycles, respectively. Four more minutes (20 additional test cycles) caused a further decrease of the platelet count only in sheep PRP. When the silicon tube was partly filled with glass beads, these effects were more pronounced and stronger in sheep then in human PRP. The mean platelet volume, which was used as parameter for platelet aggregation, did not change over time in human PRP without glass exposure. With glass exposure in human and sheep PRP the mean platelet volume increased within 40 test cycles, but this increase was stronger in sheep than in human PRP. Regarding activation behavior, the activation markers CD62P and CD63 were detectable only in < 30% (sheep) and < 45% (human) of platelets, whereas after 8 min of glass exposure, the proportion of CD62P+ and CD63+ cells was more increased than before only in sheep. These results indicate that ovine platelets adhere more strongly to glass and show stronger aggregation behavior after glass contact than human platelets, but that ovine and human platelets differ only slightly in activability by glass.

Evaluation of Antithrombogenic pHPC on CoCr Substrates for Biomedical Applications

Bare metal endovascular implants pose a significant risk of causing thrombogenic complications. Antithrombogenic surface modifications, such as phenox’s “Hydrophilic Polymer Coating” (pHPC), which was originally developed for NiTi implants, decrease the thrombogenicity of metal surfaces. In this study, the transferability of pHPC onto biomedical CoCr-based alloys is examined. Coated surfaces were characterized via contact-angle measurement and atomic force microscopy. The equivalence of the antithrombogenic effect in contact with whole human blood was demonstrated in vitro for CoCr plates compared to NiTi plates on a platform shaker and for braided devices in a Chandler loop. Platelet adhesion was assessed via scanning electron microscopy and fluorescence microscopy. The coating efficiency of pHPC on CoCr plates was confirmed by a reduction of the contact angle from 84.4° ± 5.1° to 36.2° ± 5.2°. The surface roughness was not affected by the application of pHPC. Platelet adhesion was significantly reduced on pHPC-coated specimens. The platelet covered area was reduced by 85% for coated CoCr plates compared to uncoated samples. Uncoated braided devices were completely covered by platelets, while on the pHPC-coated samples, very few platelets were visible. In conclusion, the antithrombogenic effect of pHPC coating can be successfully applied on CoCr plates as well as stent-like CoCr braids.

Comparison of Efficacy, Embolism Rate and Safety of Thrombectomy with Stent Retrievers in an Anterior Circulation Stroke Model

Purpose Various stent retrievers differing in stent design and mechanical properties are currently available for the treatment of ischemic stroke. We conducted this in vitro study to compare the efficacy, embolism rate, and safety of commercially available stent retrievers and prototypes. Materials and Methods Whole blood thrombi were produced in a Chandler loop. The thrombi were inserted into the curved M1 segment of a silicone model of the anterior cerebral circulation. Thrombectomy maneuvers were performed with six commercially available stent retrievers and 2 prototypes with different strut thickness. Wall-stent apposition, first pass recanalization rate, retraction force, and embolism rate were compared. Results Devices with complete wall-stent apposition had the highest first pass recanalization rate and lowest embolism rate, but showed the highest retraction force. The prototype with thinner struts had a comparable recanalization and embolism rate, while a lower retraction force had to be applied compared to the prototype with thicker struts. Conclusion Complete wall-stent apposition facilitates a higher recanalization rate and lower embolism rate but also correlates to a higher necessary retraction force and thus possibly higher risk of endothelium damage. Stent modifications leading to a reduced retraction force do not compromise efficacy and embolism rate. Key Points: Citation Format

Abstract 191: Immobilized ApoA-I and High Density Lipoproteins are Anti-thrombotic and Inhibit Smooth Muscle Cell Attachment and Proliferation

Aim: The clinical efficacy of current endovascular stents is limited by thrombosis and restenosis. Plasma activated coated stainless steel (PAC) is able to covalently bind proteins to stainless steel (SS) surfaces in their bioactive state. High density lipoproteins (HDL) and its main apolipoprotein constituent apoA-I regulate key biological processes involved in restenosis and thrombosis, highlighting their potential for immobilization on PAC stent surfaces. We hypothesized that covalently bound apoA-I or reconstituted HDL (rHDL) to PAC will retain its biological properties and improve stent patency. Methods and Results: Covalent binding of 125I labelled apoA-I and rHDL was increased on PAC compared to SS (p<0.001). Thrombosis formation under static conditions was assessed by scanning electron microscopy. Thrombi were strikingly reduced on PAC and completely absent on PAC+apoA-I and PAC+rHDL, while extensive thrombi formed on all SS samples at all time points. Thrombus formation under flow conditions using a Chandler Loop (0.5U/ml heparin) showed PAC, PAC+apoA-I and PAC+rHDL had 98%, 97% and 94% lower thrombus weights, compared to SS samples, respectively (p<0.05). Lower heparin concentrations (0.3U/ml) revealed that PAC+apoA-I and PAC+rHDL were superior to PAC alone in reducing thrombus weights (98% and 95%, respectively, p<0.01). P-selectin protein expression was measured by ELISA in the plasma from the Chandler loop assay (0.3U/ml heparin). Plasma exposed to PAC+apoA-I had reduced p-selectin levels (32%) compared to the PAC control (p<0.05). Immobilized apoA-I and rHDL on PAC reduced smooth muscle cell (SMC) attachment by 70% and 80%, respectively, p<0.05. Conversely, endothelial cell (EC) attachment was increased by 36% on PAC+apoA-I (p<0.05). Immobilized PAC+apoA-I and PAC+rHDL also reduced TNF-α-induced SMC proliferation (26% and 20% respectively), compared to the PAC control (p<0.05). Conclusion: ApoA-I and rHDL covalently bind to PAC surfaces. Immobilized apoA-I and rHDL retain their anti-thrombotic properties, inhibit SMC attachment and proliferation, and increase EC attachment. This may represent a novel site-directed approach to increase stent patency.

Abstract W MP8: Stent Retrievers Do Not Encase Clots But Hook Them Within Seconds

Introduction: Stent retriever procedures for clot removal in proximal cerebral arteries are often assumed to securely encase a clot for withdrawal. Hypothesis: We assessed the hypothesis that the interaction of a stent retriever device with a clot in proximal cerebral arteries typically leads to an encasement of the clot after a steady state of clot-device interaction is reached. Methods: We studied how two different stent retrievers (the Trevo and Aperio device) interact with clots made from human blood with a Chandler loop. Therefore, we injected 30 preformed clots of constant length but variable thickness into tapering models of the distal internal carotid artery, the main stem and M2 segments of the middle cerebral artery and filled the remaining lumina with x-ray contrast agent. We then performed stent retrieving procedures with high resolution biplane angiographical imaging to capture all phases of the retrieving procedure without aspiration. We measured penetration depth of the stent struts into the clots, occurrences of clot rupture and the time intervals until a steady state of penetration was achieved. Results: For both stents, we measured stent penetration depth in 60 evenly spaced positions for luminal diameters between 4.2mm and 1.3mm. Above a clot thickness of 2.3mm (Aperio) and 2.1mm (Trevo), a steady state penetration width of 0.5 mm (SD: 0.3 mm) for Trevo and 0.8 mm (SD: 0.4 mm) for Aperio was observed after 2.2s (Trevo) and 5.8 seconds (Aperio) and no encasement was observed. Below a clot thickness of 2 mm, clots were completely encased in 41% (Trevo) and 58% (Aperio), although in both both stents more than 80 % were disrupted. The steady state of penetration was achieved after 3.5s (Trevo, SD: 1.8 s) and 4.8 s (Aperio, SD: 2.1 s). Conclusions: Instead of being encased, thick clots are eccentrically attached to the outer surface of stent retrievers within a few seconds until steady state is reached. This results in the risk of stripping off the clots at the entrance of an aspiration catheter. Encasement of clots is only observed in thin clots at the price of clot disruption with a steady state after a few seconds. Both aspects imply that stent-retriever procedures can only be effective with additional close distance aspiration.