Impact of non-di-(2-ethylhexyl)phthalate cardiopulmonary bypass tubes on inflammatory cytokines and coagulation-fibrinolysis systems during cardiopulmonary bypass

Di-(2-ethylhexyl)phthalate (DEHP), an excellent plasticizer for poly(vinyl chloride) (PVC), is a known endocrine-disrupting chemical. This study was designed to investigate whether a new non-DEHP bilayer tube reduced the release of DEHP, suppressed inflammatory cytokines, and altered coagulation-fibrinolysis systems. Sixteen patients undergoing coronary artery bypass grafting (CABG) were randomly assigned to the non-DEHP bilayer group (group B, n = 8), or the noncoated PVC group (group N, n = 8). The level of DEHP in the blood was measured before and after cardiopulmonary bypass (CPB). The levels of interleukin-6 (IL-6), D-dimer, and thrombin-antithrombin complex (TAT) were also measured at six points during and after CPB. DEHP was significantly lower in group B (472 ± 141 ng/ml) after CPB compared with group N (2094 ± 1046 ng/ml). The IL-6 level was significantly lower in group B (151 ± 131 pg/ml) than group N (206 ± 224 pg/ml) 180 min after protamine administration. The D-dimer level was significantly lower in group B 60 min after protamine administration (6.2 ± 2.4 μg/ml in group B vs 10.4 ± 4.5 μg/ml in group N) and 180 min after protamine administration (4.4 ± 0.7 μg/ml in group B vs 7.3 ± 2.7 μg/ml in group N). Group B had a tendency toward reduced postoperative bleeding compared with group N at any time. The bilayer tube was superior to the noncoated tube in terms of the inhibition of DEHP release, inflammatory cytokines, and the fibrinolysis system.

[1]  M. Luyckx,et al.  Comparative study of the leachability of di(2-ethylhexyl) phthalate and tri(2-ethylhexyl) trimellitate from haemodialysis tubing. , 2001, International journal of pharmaceutics.

[2]  G. Schultze,et al.  Formation of Thrombin-Antithrombin III Complex Using Polyamide and Hemophan Dialyzers , 1992, The International journal of artificial organs.

[3]  M. Nakayama,et al.  [Extraction of di-2-ethylhexyl phthalate from a cardiopulmonary bypass circuit]. , 2001, Kyobu geka. The Japanese journal of thoracic surgery.

[4]  R. Rubin,et al.  Extracorporeal membrane oxygenation exposes infants to the plasticizer, di(2-ethylhexyl)phthalate. , 1997, Critical care medicine.

[5]  Gerhard Ziemer,et al.  Hemocompatibility of heparin-coated surfaces and the role of selective plasma protein adsorption. , 2002, Biomaterials.

[6]  M. Marinovich,et al.  Leachability of a new plasticizer tri-(2-ethylhexyl)-trimellitate from haemodialysis tubing. , 1988, The International journal of artificial organs.

[7]  M. Dalgaard,et al.  The acute effects of mono(2-ethylhexyl)phthalate (MEHP) on testes of prepubertal Wistar rats. , 2001, Toxicology letters.

[8]  R. Henderson,et al.  NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di(2-ethylhexyl) phthalate. , 2002, Reproductive toxicology.

[9]  J. F. Douglas,et al.  The carcinogenicity of dietary di(2-ethylhexyl) phthalate (DEHP) in Fischer 344 rats and B6C3F1 mice. , 1982, Journal of toxicology and environmental health.

[10]  H. Wendel,et al.  PVC-plasticizer DEHP in medical products: do thin coatings really reduce DEHP leaching into blood? , 2005, Perfusion.

[11]  U. Haug,et al.  Prolonged Catheter Survival in Intermittent Hemodialysis Using a Less Thrombogenic Micropatterned Polymer Modification , 2003, ASAIO journal.

[12]  S Westaby,et al.  Complement and the damaging effects of cardiopulmonary bypass. , 1983, The Journal of thoracic and cardiovascular surgery.

[13]  Y. Alarie,et al.  Effects of mono-2-ethylhexyl phthalate on the respiratory tract in BALB/c mice , 2004, Human & experimental toxicology.

[14]  S. Suehiro,et al.  Di(2-Ethylhexyl) Phthalate Exposure during Cardiopulmonary Bypass , 2008, Asian cardiovascular & thoracic annals.

[15]  H P Wendel,et al.  Coating-techniques to improve the hemocompatibility of artificial devices used for extracorporeal circulation. , 1999, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[16]  H. Zerkowski,et al.  New surface biopolymers for oxygenators: an in vitro hemocompatibility test of poly(2-methoxyethylacrylate). , 2001, European journal of medical research.

[17]  B. Lake,et al.  A cancer risk assessment of di(2-ethylhexyl)phthalate: application of the new U.S. EPA Risk Assessment Guidelines. , 1999, Regulatory toxicology and pharmacology : RTP.

[18]  T. Gourlay,et al.  Inflammatory response of rat and human neutrophils exposed to di-(2-ethyl-hexyl)-phthalate-plasticized polyvinyl chloride. , 2003, Artificial organs.

[19]  E. Fosse,et al.  Time for new concepts about measurement of complement activation by cardiopulmonary bypass? , 1992, The Annals of thoracic surgery.

[20]  W. van Oeveren,et al.  Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass. , 1993, The Annals of thoracic surgery.