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On-line Access: 2011-04-06

Received: 2010-11-08

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Crosschecked: 2011-03-16

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Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.4 P.264-272


Efficacy of a novel endotoxin adsorber polyvinylidene fluoride fiber immobilized with L-serine ligand on septic pigs

Author(s):  Jian-ping Gao, Man Huang, Ning Li, Peng-fei Wang, Huan-lin Chen, Qiu-ping Xu

Affiliation(s):  Critical Care Department, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China, Department of Chemical and Biochemical Engineering, Zhejiang University, Hangzhou 310027, China

Corresponding email(s):   xu_qp@yahoo.cn

Key Words:  Sepsis, Endotoxin, Adsorption, Polyvinylidene fluoride matrix immobilized with L-serine ligand (PVDF-Ser), Hemoperfusion, Pig

Jian-ping Gao, Man Huang, Ning Li, Peng-fei Wang, Huan-lin Chen, Qiu-ping Xu. Efficacy of a novel endotoxin adsorber polyvinylidene fluoride fiber immobilized with L-serine ligand on septic pigs[J]. Journal of Zhejiang University Science B, 2011, 12(4): 264-272.

@article{title="Efficacy of a novel endotoxin adsorber polyvinylidene fluoride fiber immobilized with L-serine ligand on septic pigs",
author="Jian-ping Gao, Man Huang, Ning Li, Peng-fei Wang, Huan-lin Chen, Qiu-ping Xu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Efficacy of a novel endotoxin adsorber polyvinylidene fluoride fiber immobilized with L-serine ligand on septic pigs
%A Jian-ping Gao
%A Man Huang
%A Ning Li
%A Peng-fei Wang
%A Huan-lin Chen
%A Qiu-ping Xu
%J Journal of Zhejiang University SCIENCE B
%V 12
%N 4
%P 264-272
%@ 1673-1581
%D 2011
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1000389

T1 - Efficacy of a novel endotoxin adsorber polyvinylidene fluoride fiber immobilized with L-serine ligand on septic pigs
A1 - Jian-ping Gao
A1 - Man Huang
A1 - Ning Li
A1 - Peng-fei Wang
A1 - Huan-lin Chen
A1 - Qiu-ping Xu
J0 - Journal of Zhejiang University Science B
VL - 12
IS - 4
SP - 264
EP - 272
%@ 1673-1581
Y1 - 2011
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1000389

A novel adsorber, polyvinylidene fluoride matrix immobilized with L-serine ligand (PVDF-Ser), was developed in the present study to evaluate its safety and therapeutic efficacy in septic pigs by extracorporeal hemoperfusion. endotoxin adsorption efficiency (EAE) of the adsorber was firstly measured in vitro. The biocompatibility and hemodynamic changes during extracorporeal circulation were then evaluated. One half of 16 pigs receiving lipopolysaccharide (Escherichia coli O111:B4, 5 μg/kg) intravenously in 1 h were consecutively treated by hemoperfusion with the new adsorber for 2 h. The changes of circulating endotoxin and certain cytokines and respiratory function were analyzed. The 72 h-survival rate was assessed eventually. EAE reached 46.3% (100 EU/ml in 80 ml calf serum) after 2 h-circulation. No deleterious effect was observed within the process. The plasma endotoxin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were decreased during the hemoperfusion. Arterial oxygenation was also improved during and after the process. Furthermore, the survival time was significantly extended (>72 h vs. 47.5 h for median survival time). The novel product PVDF-Ser could adsorb endotoxin with high safety and efficacy. Early use of extracorporeal hemoperfusion with the new adsorber could reduce the levels of circulating endotoxin, IL-6, and TNF-α, besides improve respiratory function and consequent 72 h-survival rate of the septic pigs. endotoxin removal strategy with blood purification using the new adsorber renders a potential promising future in sepsis therapy.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Amoureux, M.C., Rajapakse, N., Hegyi, E., Le, D., Grandics, P., Szathmary, S., 2004. Endotoxin removal from whole blood by a novel adsorption resin: efficiency and hemocompatibility. Int. J. Artif. Organs, 27(6):480-487.

[2]Angus, D.C., Birmingham, M.C., Balk, R.A., Scannon, P.J., Collins, D., Kruse, J.A., Graham, D.R., Dedhia, H.V., Homann, S., Maclntyre, N., 2000. E5 murine monoclonal antiendotoxin antibody in Gram-negative sepsis: a randomized controlled trial. JAMA, 283(13):1723-1730.

[3]Bengsch, S., Boos, K.S., Nagel, D., Seidel, D., Inthorn, D., 2005. Extracorporeal plasma treatment for the removal of endotoxin in patients with sepsis: clinical results of a pilot study. Shock, 23(6):494-500.

[4]Bernard, G.R., Vincent, J.L., Laterre, P.F., LaRosa, S.P., Dhainaut, J.F., Lopez-Rodriguez, A., Steingrub, J.S., Garber, G.E., Helterbrand, J.D., Ely, E.W., et al., 2001. Efficacy and safety of recombinant human activated protein C for severe sepsis. N. Engl. J. Med., 344(10):699-709.

[5]Bracht, H., Hauser, B., Ivanyi, Z., Asfar, P., Ehrmann, U., Brueckner, U.B., Georgieff, M., Radermacher, P., Buttenschon, K., 2009. Efficacy of an extracorporeal endotoxin adsorber system during hyperdynamic porcine endotoxemia. Eur. Surg. Res., 43(1):53-60.

[6]Carlsson, M., Lipcsey, M., Larsson, A., Tano, E., Rubertsson, S., Eriksson, M., Sjolin, J., 2009. Inflammatory and circulatory effects of reduction of endotoxin concentration in established porcine endotoxemic shock—a model of endotoxin elimination. Crit. Care Med., 37(3):1031-1037.

[7]Cheng, B., Xie, G., Yao, S., Wu, X., Guo, Q., Gu, M., Fang, Q., Xu, Q., Wang, D., Jin, Y., et al., 2007. Epidemiology of severe sepsis in critically ill surgical patients in ten university hospitals in China. Crit. Care Med., 35(11):2538-2546.

[8]Cruz, D.N., Perazella, M.A., Bellomo, R., de Cal, M., Polanco, N., Corradi, V., Lentini, P., Nalesso, F., Ueno, T., Ranieri, V.M., et al., 2007. Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review. Crit. Care, 11(2):R47.

[9]Cruz, D.N., Antonelli, M., Fumagalli, R., Foltran, F., Brienza, N., Donati, A., Malcangi, V., Petrini, F., Volta, G., Bobbio Pallavicini, F.M., et al., 2009. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA, 301(23):2445-2452.

[10]Gritters-van den Oever, M., Schoorl, M., Schoorl, M., Bartels, P.C., Grooteman, M.P., Nube, M.J., 2009. The role of the extracorporeal circuit in the trapping and degranulation of platelets. Blood Purif., 28(3):253-259.

[11]Howell, C.A., Sandeman, S.R., Phillips, G.J., Lloyd, A.W., Davies, J.G., Mikhalovsky, S.V., Tennison, S.R., Rawlinson, A.P., Kozynchenko, O.P., Owen, H.L., et al., 2006. The in vitro adsorption of cytokines by polymer-pyrolysed carbon. Biomaterials, 27(30):5286-5291.

[12]Jaber, B.L., Pereira, B.J., 1997. Extracorporeal adsorbent-based strategies in sepsis. Am. J. Kidney Dis., 30(5):S44-S56.

[13]Klinge, U., Klosterhalfen, B., Ottinger, A.P., Junge, K., Schumpelick, V., 2002. PVDF as a new polymer for the construction of surgical meshes. Biomaterials, 23(16):3487-3493.

[14]Marshall, J.C., Foster, D., Vincent, J.L., Cook, D.J., Cohen, J., Dellinger, R.P., Opal, S., Abraham, E., Brett, S.J., Smith, T., et al., 2004. Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J. Infect. Dis., 190(3):527-534.

[15]Martin, G.S., Mannino, D.M., Eaton, S., Moss, M., 2003. The epidemiology of sepsis in the United States from 1979 through 2000. N. Engl. J. Med., 348(16):1546-1554.

[16]McCloskey, R.V., Straube, R.C., Sanders, C., Smith, S.M., Smith, C.R., 1994. Treatment of septic shock with human monoclonal antibody HA-1A. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med., 121(1):1-5.

[17]Nakamura, M., Oda, S., Sadahiro, T., Hirayama, Y., Watanabe, E., Tateishi, Y., Nakada, T.A., Hirasawa, H., 2010. Treatment of severe sepsis and septic shock by CHDF using a PMMA membrane hemofilter as a cytokine modulator. Contrib. Nephrol., 166:73-82.

[18]Neuss, S., Apel, C., Buttler, P., Denecke, B., Dhanasingh, A., Ding, X., Grafahrend, D., Groger, A., Hemmrich, K., Herr, A., et al., 2008. Assessment of stem cell/biomaterial combinations for stem cell-based tissue engineering. Biomaterials, 29(3):302-313.

[19]Opal, S.M., 2002. The clinical relevance of endotoxin in human sepsis: a critical analysis. J. Endotoxin Res., 8(6):473-476.

[20]Rigato, O., Ujvari, S., Castelo, A., Salomao, R., 1996. Tumor necrosis factor alpha (TNF-α) and sepsis: evidence for a role in host defense. Infection, 24(4):314-318.

[21]Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., Tomlanovich, M., 2001. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N. Engl. J. Med., 345(19):1368-1377.

[22]Shimizu, T., Endo, Y., Tsuchihashi, H., Akabori, H., Yamamoto, H., Tani, T., 2006. Endotoxin apheresis for sepsis. Transfus. Apher. Sci., 35(3):271-282.

[23]Shoji, H., 2003. Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin). Ther. Apher. Dial., 7(1):108-114.

[24]Song, M., Kellum, J.A., 2005. Interleukin-6. Crit. Care Med., 33(12 Suppl.):S463-S465.

[25]Stegmayr, B., 2008. Apheresis in patients with severe sepsis and multi organ dysfunction syndrome. Transfus. Apher. Sci., 38(3):203-208.

[26]Sun, H., Zhang, L., Chai, H., Chen, H., 2005. Removing endotoxin from protein solution by chitosan modified affinity membrane. Chin. J. Chem. Eng., 13(4):457-463.

[27]Sun, H., Zhang, L., Chai, H., Yu, J., Qian, H., Chen, H., 2006. A study of human γ-globulin adsorption capacity of PVDF hollow fiber affinity membranes containing different amino acid ligands. Sep. Purif. Technol., 48(3):215-222.

[28]Taniguchi, T., Kurita, A., Mukawa, C., Yamamoto, K., Inaba, H., 2007. Dose-related effects of direct hemoperfusion using a cytokine adsorbent column for the treatment of experimental endotoxemia. Intensive Care Med., 33(3):529-533.

[29]Tetta, C., Bellomo, R., Inguaggiato, P., Wratten, M.L., Ronco, C., 2002. Endotoxin and cytokine removal in sepsis. Ther. Apher. Dial., 6(2):109-115.

[30]Tsushima, K., Kubo, K., Koizumi, T., Yamamoto, H., Fujimoto, K., Hora, K., Kan-Nou, Y., 2002. Direct hemoperfusion using a polymyxin B immobilized column improves acute respiratory distress syndrome. J. Clin. Apher., 17(2):97-102.

[31]Umgelter, A., Reindl, W., Lutz, J., Kreymann, B., Ronco, C., Huber, W., Frank, H., Schmid, R.M., Heemann, U., 2008. Treatment of septic patients with an arginine-based endotoxin adsorber column improves hemodynamics and reduces oxidative stress: results of a feasibility study. Blood Purif., 26(4):333-339.

[32]van der Poll, T., 2001. Immunotherapy of sepsis. Lancet Infect. Dis., 1(3):165-174.

[33]Vincent, J.L., Sakr, Y., Sprung, C.L., Ranieri, V.M., Reinhart, K., Gerlach, H., Moreno, R., Carlet, J., Le Gall, J.R., Payen, D., et al., 2006. Sepsis in European intensive care units: results of the SOAP study. Crit. Care Med., 34(2):344-353.

[34]Wei, Z., Huang, W., Li, J., Hou, G., Fang, J., Yuan, Z., 2007. Studies on endotoxin removal mechanism of adsorbents with amino acid ligands. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci., 852(1-2):288-292.

[35]Wong, K.F., Luk, J.M., 2009. Endotoxin-neutralizing peptides as Gram-negative sepsis therapeutics. Protein Pept. Lett., 16(5):539-542.

[36]Zagli, G., Bonizzoli, M., Spina, R., Cianchi, G., Pasquini, A., Anichini, V., Matano, S., Tarantini, F., Di Filippo, A., Maggi, E., et al., 2010. Effects of hemoperfusion with an immobilized polymyxin-B fiber column on cytokine plasma levels in patients with abdominal sepsis. Minerva Anestesiol., 76(6):405-412.

[37]Zanotti-Cavazzoni, S.L., Goldfarb, R.D., 2009. Animal models of sepsis. Crit. Care Clin., 25(4):703-719.

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