| Currently, cardiopulmonary bypass (CPB) has been proved to be a routine technique applied in cardiac surgery. However, the biocompatibility of artificial materials used in CPB is far from ideal. When blood comes into contact with these materials, it may cause serious postoperative systemic inflammatory response, and thus affects patients, clinical outcomes. Previous studies have demonstrated that heparin coating can improve the biocompatibility of CPB materials and reduce the systemic inflammatory response after cardiac surgery. But heparin coating also has the limitation of non-selective plasma protein adsorption, inexact anticoagulation effects and needs to be modified and improved. Meanwhile, there is no commercially domestic-made heparin coating products available at present. Therefore, basing on the successful development of polyethyleneimine-glutaraldehyde (PEI-G) bonding technique, this study innovatively synthesises sodium periodate-oxidated low molecular weight heparin-antithrombin complex (SPLMWATH) and links it to polyvinyl chloride (PVC) tubing applied in CPB, with the hope of developing a new surface modification technique for CPB circuit surface with independent intellectual property rights, further improving the biocompatibility of CPB circuit materials, eventually being applied to clinical use, reducing the mortality and complications and improving the operation results.Part I: Preparation and physico-chemical characterization of SPLMWATH: Basing on non-enzymatic protein glycated reaction, the SPLMWATH was produced. By using PEI-G bonding technique, PVC tubings were coated with SPLMWATH, heparin and LMWH. Spectrophotometry and dynamic clotting time experiment were used to determinate the synthetic ratio of SPLMWATH, graft density, coating leaching ratio and to evaluate the antithrombogenicity of the three coating PVC tubings. Results: The synthetic ratio of SPLMWATH was approximately 55%. Their graft densities (mol/cm2) were 1.83×10-11±1.63×10-12, 1.02×10-10±1.36×10-11 and 3.71×10-10±2.29×10-11, respectively. After soaked in saline for 1 month, the coating leaching ratios(%) were 0.58±0.10, 0.85±0.14 and 0.92±0.18, respectively. The leaching ratio of SPLMWATH coating was significantly lower than that of heparin coating and LMWH coating (P<0.05). Curves of dynamic clotting time showed that the antithrombogenicity of SPLMWATH coating was significantly better than that of heparin coating and LMWH coating.Part II: There were five groups: control group, non-coated group, heparin-coated group, LMWH-coated group and SPLMWATH-coated group. Human anticoagulant whole blood was incubated in rotating PVC tubing for 4 hours, using Chandlar loop model. The platelet count, content of fibrinogen in plasma and plasma concentrations of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were quantified. Scanning electron microscope (SEM) was used to observe the internal surface of each group tubing. Results: The platelet count (×109/L) and content of fibrinogen in plasma (g/L) were both decreased in all groups when compared with their baseline values (198±22 and 2.75±0.56), and the decreasing degree of SPLMWATH-coated group (174±20 and 2.55±0.55) were the minimums among them. There were significant differences between SPLMWATH-coated group and heparin-coated group (109±19 and 1.50±0.35) as well as SPLMWATH-coated group and LMWH-coated group (150±17 and 1.95±0.33) (P<0.05). Also, there were significant differences between heparin-coated group and LMWH-coated group (P<0.05). Plasma concentrations of the IL-8 and MCP-1 (pg/ml) were both increased in all groups when compared with their baseline values (33±6 and 27±2), and the increasing degree of SPLMWATH-coated group (278±24 and 110±10)were the minimums among them. There were significant differences between SPLMWATH-coated group and heparin-coated group (446±48 and 168±20) as well as SPLMWATH-coated group and LMWH-coated group (417±38 and 157±17) (P<0.05). But no significant differences between heparin-coated group and LMWH-coated group were found (P>0.05). Results of SEM showed heparin-coated group, LMWH-coated group and SPLMWATH-coated group can reduce the adhesion of platelets and fibrin when compared with non-coated group. The outcome of SPLMWATH-coated group was much better than that of heparin-coated group and LMWH-coated group, and LMWH-coated group was slightly superior to heparin-coated group.Conclusion: 1. The SPLMWATH is synthesized successfully, and its synthetic ratio is approximately 55%; 2. Compared with heparin coating and LMWH coating, the graft density of SPLMWATH coating PVC tubing is lesser, but its coating stability and antithrombogenicity are significantly better than that of heparin coating and LMWH coating; 3. SPLMWATH-coated PVC tubing is better than heparin-coated and LMWH-coated PVC tubing in biocompatibility, alleviating the blood-PVC contacting-induced production and releasing of inflammatory mediators and coagulation activation.
|
PDF Full Text Request