Efficacy of a novel endotoxin adsorber polyvinylidene fluoride fiber immobilized with (L)-serine ligand on septic pigs |
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| Authors: | Gao Jian-ping Huang Man Li Ning Wang Peng-fei Chen Huan-Lin Xu Qiu-ping |
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| Institution: | (1) Department of Surgery, Shiga University of Medical Science, Seta-tsukinowacho, Otsu, Shiga 520-2192, Japan;(2) Department of Critical and Emergency Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan;(3) Juntendo University Shizuoka Hospital, Shizuoka, Japan;(4) Hyogo Prefectural Awaji Hospital, Sumoto, Hyogo, Japan;(5) Shinkoga Hospital, Saga, Japan;(6) Saiseikai Matsusaka General Hospital, Matsusaka, Mie, Japan;(7) Saga University Hospital, Saga, Japan;(8) Takagi Hospital, Fukuoka, Japan;(9) Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan;(10) National Defense Medical College, Tokorozawa, Japan;(11) Kanazawa Medical University, Kanazawa, Japan;(12) Higashiyamato Hospital, Tokyo, Japan;(13) Sagamidai Hospital, Zama, Kanagawa, Japan |
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| Abstract: | 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. |
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| Keywords: | Sepsis Endotoxin Adsorption Polyvinylidene fluoride matrix immobilized with l-serine ligand (PVDF-Ser) Hemoperfusion Pig |
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