Effect of biopassive and bioactive surface-coatings on the hemocompatibility of membrane oxygenators.

Postoperative complications associated with cardiopulmonary bypass (CPB) surgery and extracorporeal circulation (ECC) procedures are still a major clinical issue. Improving the hemocompatibility of blood contacting devices used for ECC procedures may ameliorate various postpump syndromes. In a simulated CPB model using human blood, we investigated the hemocompatibility, fibrinogen adsorption, and platelet receptor (GPIIb-IIIa) binding capacity of surface-modified membrane oxygenators (Jostra Quadrox). Three groups were compared: (i) biopassive protein coatings (SafeLine), (ii) bioactive heparin coatings (BioLine), and (iii) noncoated controls. During the 2 h recirculation period, plasma concentrations of activation markers for platelets (beta-thromboglobulin), inflammation (elastase), complement (C5a), and coagulation (prothrombin fragment 1+2, thrombin-antithrombin III) were lower in the groups with biopassive and bioactive coatings compared to the noncoated group (p < 0.01). These parameters did not significantly differ between the two surface-coated groups, except for complement activation: C5a levels were higher in the biopassive group compared to the bioactive group (p < 0.01). Moreover, surface-coated oxygenators showed less fibrinogen adsorption, GPIIb-IIIa binding, and platelet/leukocyte adhesion (p < 0.01). We assume that fewer fibrinogen and platelet receptor molecules bound to the surface-coated oxygenator surfaces results in fewer platelet adhesion and activation, which will significantly contribute to the improved hemocompatibility of the biopassive and bioactive oxygenators. Our results suggest that the application of bioactive oxygenators (BioLine) during CPB surgery may reduce postoperative complications for the patient more effectively than biopassive oxygenators (SafeLine).

Thrombospondin 1 as possible key factor in the hemocompatibility of endocoronary prostheses.

Intracoronary stenting has markedly improved the patency of native coronary arteries after percutaneous transluminal coronary angioplasty (PTCA). Advances in stent technology and design, including drug releasing stents, have contributed to reduce the long-term restenosis rate. However, stenosis caused by neointimal hyperplasia, vascular remodeling and thrombosis is still a major problem after endocoronary stent procedures. This study focuses on differential gene expression of circulating peripheral blood cells after 90 min exposure to stents to search for initially activated cellular pathways, which may foster restenosis. Fresh human whole blood (1 IU heparin/ml), taken from non-medicated healthy volunteers, was incubated under flow conditions in an in vitro closed-loop stent-testing model (modified Chandler-Loop). Differential gene expression compared to resting conditions and to the experimental controls was investigated by a DNA-microarray technique encoding for over 17,000 genes simultaneously. As expected, a large variety of genes showed differential gene expression. Interestingly, Thrombospondin 1 (TSP-1), which plays a key role in initial immune defense, was found to be the most markedly up-regulated gene. We propose TSP-1 expression as an early indicator for the activation of immune responses following intracoronary stenting. After clarifying the participation of TSP-1 in vivo, future studies will therefore focus on TSP-1 as a potential prognostic factor, which may also help to develop and control new surface materials with an improved biocompatibility.

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.

Cytokine gene expression in monocytes of patients undergoing cardiopulmonary bypass surgery evaluated by real-time PCR.

Cardiopulmonary bypass (CPB) surgery induces systemic release of proinflammatory cytokines causing unspecific inflammatory reactions. This study deals with the development of a sensitive technique for detecting changes at the mRNA level in monocytes of patients undergoing CPB surgery, by using real-time PCR. Blood samples from patients undergoing elective coronary artery bypass grafting were obtained at six different time points. RNA was extracted from isolated monocytes and cDNA was synthesized by reverse transcriptase. CPB surgery induced gene expression of IL-1beta, IL-6, IL-8, and TNF-alpha, followed by a decrease below the preoperative expression values 6 h post CPB. High significant increases in gene expression for IL-8 at the end of surgery (p = 0.001) were detected. Real-time PCR is a powerful tool for getting simultaneously numerous sensitive, accurate, and reliable results from small amounts of biological material. This method avoids time-consuming and hazardous post-PCR manipulations and decreases the potential risk of PCR contamination.