Hemocompatibility of medical connectors with biopassive or bioactive surface coatings

Although medical connectors compose very small parts of the extracorporeal circulation (ECC) system they represent a critical localization where early thromboembolic processes can manifest. In the present study we modified an in vitro closed-loop model with fresh human whole blood for the preclinical evaluation of the hemocompatibility of three types of medical connectors: non-coated (control); with silicone-, and heparin-coating. Each single loop consists of five polycarbonate connectors joined together by five pieces of silicone tubes. Thrombin-antithrombin-III, beta-thromboglobulin (beta-TG), PMN-Elastase, terminal complement complex, CD 11b expression, and surface-absorbed fibrinogen were measured. After 1 and 2 h recirculation, platelet loss, release of beta-TG, and adsorption of fibrinogen were significantly higher (p<0.05) within the non-coated connectors compared to the silicone- and heparin-coated groups. Following this experiment, the connectors were filled again with fresh heparinized whole blood from the same donor to evaluate the influence of prior blood contact. Here, the activation of platelets and coagulation was dependent on the duration of the blood preincubation period. Probably, the coated surfaces possess a reduced, or selective adsorption of plasma proteins, which in turn leads to a faster creation of a blood-friendly secondary superficial membrane, and prevents a further denaturation and hence activation of the adsorbed proteins.     

Quality assessment of heparin coatings by their binding capacities of coagulation and complement enzymes

In vitro testing of blood contacting materials before clinical application is generally advisable. Four heparin coatings from different manufacturers were tested for adsorbed proteins and soluble activation markers. The surface with the highest antithrombin, thrombin, high-molecular-weight-kininogen (HMWK) and the lowest fibrinogen binding capacity (Carmeda, Medtronic) showed significantly lower levels of granulocytes and platelet activation (beta-TG, PMN-elastase release). No statistically significant differences in soluble markers of the coagulation system could be detected (F1 + 2, TAT). Interestingly, complement activation (TCC) was significantly reduced within the group of the lowest adsorption of the complement factor C3. Our data demonstrate that there is a relation between the binding affinity of proteins (C1-inhibitor, C3-complement) and the consecutive changes in complement activation (TCC). Therefore, measuring adsorbed proteins on artificial surfaces is a suitable, sensitive and very reproducible method for assessing the thrombogenicity of biomaterials.     

Hemocompatibility of PMEA coated oxygenators used for extracorporeal circulation procedures

An inflammatory response to cardiopulmonary bypass (CPB) caused by bioincompatibility of extracorporeal circuits is one of the major clinical issues in cardiac surgery. Recently a new coating material, poly-2-methoxyethylacrylate (PMEA), was developed to improve the biocompatibility of blood contacting surfaces. In a simulated cardiopulmonary bypass model, using fresh human whole blood, 15 membrane oxygenators (Capiox SX18, Terumo Corp., Tokyo, Japan) were compared. Five of them had the PMEA coating, five had a heparin-coated surface, and five had no surface treatment. Blood samples were taken at several time-points during a 90 minute circulation period. Changes in coagulation, complement, and blood cell alteration factors were measured by ELISA methods, plasma bradykinin levels were measured by radioimmunoassay, and expression of genes encoding cytokines TNF-alpha, interleukin-1beta, interleukin-6, and interleukin-8 was determined by semiquantitative real time RT-PCR. Platelet adhesion was significantly reduced in both the PMEA and the heparin coated circuits. Release of platelet activation marker beta-thromboglobulin was significantly higher in the uncoated control group (p < 0.01). After 5 minutes of blood circulation bradykinin levels significantly increased in all three groups (p < 0.01); however, the group with the PMEA coated oxygenators showed the lowest values. Expression of genes encoding proinflammatory cytokines in monocytes was increased in all groups, with the lowest being in the PMEA coated group. PMEA coated CPB surfaces in an in vitro experimental model showed an improved thrombogenicity, reduced bradykinin release, less platelet activation and less proinflammatory cytokines gene expression in comparison with a noncoated group. The authors assume that PMEA coating may ameliorate some of intra- and postperfusion syndromes, particularly hypotension, unspecific inflammation, hyperfibrinolysis, and blood loss.     

Increased adsorption of high molecular weight kininogen to heparin-coated artificial surfaces and correlation to hemocompatibility

During the past 10 years investigations have demonstrated that heparin-coated devices used for extracorporeal circuits show an improved hemocompatibility. We investigated the pathway of adsorption of plasma proteins at heparin-coated artificial surfaces and the further activation of the humoral and cellular defense mechanisms of the blood. Twenty milliliters of fresh human blood (1 IU heparin/ml) filled a 50 cm long tubes (with and without covalent heparin-coating), prepared as an in vitro "Closed-Loop" model and recirculated at a temperature of 37 degrees C. After 5, 15, 30, 60 and 120 min fibrinogen and high molecular weight kininogen (HMWK) adsorption was measured by a newly developed modified ELISA technique. In addition, changes in coagulation and platelet activation were measured by well established assays. High concentrations of fibrinogen were detected after very short blood material contact, both on uncoated as well as heparin-coated tubes. However, high amounts of HMWK were only found on the heparin-bonded surfaces. In addition, the concentrations of the soluble coagulation marker prothrombin fragment F1+2 and the marker for platelet activation beta-thromboglobulin were significantly higher in the non-coated tubes. We presume that adsorption of HMWK to heparin-coated surfaces contributes to the improved hemocompatibility of these bondings.     

To participate or not participate in unprofessional behavior – Is that the question?

Introduction: Medical education provides students with abundant learning opportunities, each of which is embodied with messages concerning what is expected from students. This paper analyses students? exposure to instances of unprofessional behavior, investigating whether they judge such behavior to be unprofessional and whether they also participate in unprofessional behavior.

Methods: The survey developed in the Pritzker School of Medicine at the University of Chicago was the basis of this questionnaire that was answered by 276 students from two medical schools in Brazil and Portugal.

Results: Unprofessional behavior was observed frequently by students in both universities, and the mean participation rates were similar (26% and 27%). Forty-five percent of students? participation in unprofessional behavior was explained by academic year, prior observation, and judgment.

Discussion: The results indicate that once students have observed, participated in or misjudged unprofessional behavior, they tend to participate in and misjudge such behavior. The frequency with which students judged behaviors they had observed or participated in as ?borderline? or unprofessional could mean that they are experiencing moral distress.

Conclusion: Proper discussion of unprofessional behavior should foster a broad debate to encourage empowered students, faculties, and physicians to co-create a more professional environment for patient care.     

Right-sided cervical aortic arch with stenosis--treatment with an extra-anatomic bypass graft

Right-sided cervical aortic arch is a very rare vascular anomaly that may lead to stenosis development. Anatomic repair may be impeded by its high course or by abnormal branching of the supraaortic vessels, or both. This report will describe the treatment of a stenotic right-sided cervical aortic arch using an extra-anatomic bypass graft without extracorporeal support in an 11-year-old girl.