Abstract
To evaluate effects of polymyxin B direct hemoperfusion (PMX-DHP) on a neonatal sepsis cecal ligation and perforation (CLP) model, in 24 anesthetized and mechanically ventilated 3-d-old piglets, 16 were assigned to CLP and an arteriovenous extracorporeal circuit from 3 h until 6 h post-CLP, with a PMX-column in PMX-DHP–treated group (8 piglets) and 8 as sham. Plasma lipopolysaccharide (LPS) was measured at before CLP and at 3 and 9 h. Changes in mean systemic blood pressure (mSBP), mean pulmonary blood pressure, serum IL-6, tumor necrosis factor alpha, interferon gamma, and highly mobile group-1 box protein were measured before CLP and at 1, 3, 6, and 9 h. LPS was lower in the sham and PMX-DHP groups than in the control at 9 h. The mSBP was higher in the sham and PMX-DHP groups than in the control at both 6 h. IL-6 was lower in the sham and PMX-DHP groups than in the control at 6 h. HMGB-1 was lower in the PMX-DHP group than in the control at 6 h. IFN-γ was only detected in the control group at 9 h. Survival times in the PMX-DHP group were longer than in the control. Thus, PMX-DHP improved septic shock in a neonatal septic model.
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Abbreviations
- CLP:
-
cecal ligation and perforation
- CVP:
-
central venous pressure
- HMGB-1:
-
highly mobile group-1 box protein
- IFN-γ:
-
interferon gamma
- LPS:
-
lipopolysaccharide (endotoxin)
- mPAP:
-
mean pulmonary blood pressure
- mSBP:
-
mean systemic blood pressure
- PMX-DHP:
-
polymyxin B direct hemoperfusion
- TNF-α:
-
tumor necrosis factor alpha
References
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR 2001 Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29: 1303–1310
Postpartum care of mother and newborn: a practical guide. WHO/RHT/MSM/98.3
Hack CE, Aarden LA, Thijs LG 1997 Role of cytokines in sepsis. Adv Immunol 66: 101–195
Silveira RC, Procianoy RS 1999 Evaluation of interleukin-6, tumor necrosis factor-alpha and interleukin-1beta for early diagnosis of neonatal sepsis. Acta Paediatr 88: 647–650
Casey LC, Balk RA, Bone RC 1993 Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 119: 771–778
Sullivan JS, Kilpatrick L, Costarino AT Jr, Lee SC, Harris MC 1992 Correlation of plasma cytokine elevations with mortality rate in children with sepsis. J Pediatr 120: 510–515
Yin K, Hock CE, Lai PS, Ross JT, Yue G 1999 Role of interferon-γ in lung inflammation following cecal ligation and puncture in rats. Shock 12: 215–221
Qiu G, Wang C, Smith R, Harrison K, Yin K 2001 Role of IFN-γ in bacterial containment in a model of intra-abdominal sepsis. Shock 16: 425–429
Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ 1999 HMG-1 as a late mediator of endotoxin lethality in mice. Science 285: 248–251
Malchesky PS, Zborowski M, Hou KC 1995 Extracorporeal techniques of endotoxin removal: a review of the art and science. Adv Renal Replac Ther 2: 60–69
Takada H, Ogawa T, Yoshimura F, Otsuka K, Kokeguchi S, Kato K, Umemoto T, Kotani S 1988 Immunobiological activites of a porin fraction isolated from Fusobacterium nucleatum ATCC 10953. Infect Immun 56: 855–863
Rifkind D 1967 Prevention by polymyxin B of endotoxin lethality in mice. J. Bacteriol 93: 1463–1464
Corrigan JJ Jr, Kiernat JF 1979 Effect of polymyxin B sulfate on endotoxin activity in a gram-negative septicemia model. Pediatr Res 13: 48–51
Tani T, Hanasawa K, Endo Y, Yoshioka T, Kodama M, Kaneko M, Uchiyama Y, Akizawa T, Takahasi K, Sugai K 1998 Therapeutic apheresis for septic patients with organ dysfunction: hemoperfusion using a polymyxin B immobilized column. Artif Organs 22: 1038–1044
Andrew SK, Dianne EC 1996 The neonatal immune system. Semin Neonatal 1: 67–75
Kato T, Hussein MH, Sugiura T, Suzuki S, Fukuda S, Tanaka T, Kato I, Togari H 2004 Development and characterization of a novel porcine model of neonatal sepsis. Shock 21: 329–335
Grootendorst AF, van Bommel EF, van Leengoed LA, Nabuurs M, Bouman CS, Groeneveld AB 1994 High volume hemofiltration improves hemodynamics and survival of pigs exposed to gut ischemia and reperfusion. Shock 2: 72–78
Yamada S, Inoue K, Yakabe K, Imaizumi H, Maruyama I 2003 High mobility group protein 1 (HMGB-1) quantified by ELISA with monoclonal antibody that does not cross-react with HMGB2. Clin Chem 49: 1535–1537
Ray BL, Painter G, Raetz CR 1984 The biosynthesis of gram-negative endotoxin. Formation of lipid A disaccharides from monosaccharide precursors in extracts of Escherichia coli. J Biol Chem 259: 4852–4859
Freudenberg M, Galanos C 1990 Bacterial lipopolysaccharides: structure, metabolism, and mechanisms of action. Int Rev Immunol 6: 207–221
Elsbach P, Weiss J 1995 Prospects for use of recombinant BPI in the treatment of gram-negative bacterial infections. Infect Agents Dis 4: 102–109
Bone RC, Balk RA, Fein AM, Perl TM, Wenzel RP, Reines HD, Quenzer RW, Iberti TJ, Macintyre N, Schein RM 1995 A second large controlled clinical study of E5, a monoclonal antibody to endotoxin: results of a prospective, multicenter, randomized, controlled trial. The E5 Sepsis Study Group. Crit Care Med 23: 994–1005
Yamamoto H, Koizumi T, Kaneki T, Fujimoto K, Kubo K, Honda T 2002 Direct hemoperfusion with polymyxin B-immobilized fiber improves shock and hypoxemia during endotoxemia in anesthetized sheep. J Endotoxin Res 8: 419–426
Hanasawa K, Tani T, Kodama M 1989 New approach to endotoxic and septic shock by means of polymyxin B immobilized fiber. Surg Gynecol Obstet 168: 323–331
Nakamura T, Ebihara I, Shimada N, Koide H 1998 Changes in plasma erythropoietin and interleukin-6 concentrations in patients with septic shock after hemoperfusion with polymyxin B-immobilized fiber. Intensive Care Med 24: 1272–1276
Hanasawa K 2002 Extracorporeal treatment for septic patients: new adsorption technologies and their clinical application. Ther Apher 6: 290–295
Freise H, Bruckner UB, Spiegel HU 2001 Animal models of sepsis. J Invest Surg 14: 195–212
Edelson MB, Bagwell CE, Rozycki HJ 1999 Circulating pro- and counter inflammatory cytokine levels and severity in necrotizing enterocolitis. Pediatrics 103: 766–771
Goldfarb RD, Glock D, Kumar A, McCarthy RJ, Mei J, Guynn T, Matushek M, Trenholme G, Parillo JE 1996 A porcine model of peritonitis and bacteremia simulates human septic shock. Shock 6: 442–451
Cates KL, Rowe JC, Ballow M 1983 The premature infant as a compromised host. Curr Probl Pediatr 13: 1–63
Schibler KR, Liechty KW, White WL, Rothstein G, Christensen RD 1992 Defective production of interleukin-6 by monocytes: a possible mechanism underlying several host defense deficiencies of neonates. Pediatr Res 31: 18–21
Tomasz A 1986 Penicillin-binding protein and the antibacterial effectiveness of beta-lactam antibiotics. Rev Infect Dis 8: S260–S278
Morrison DC, Bucklin SE 1996 Evidence for antibiotic-mediated endotoxin release as a contributing factor to lethality in experimental gram-negative sepsis. Scand J Infect Dis Suppl 101: 3–8
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Toray Industries (Tokyo, Japan) provided the polymyxin B immobilized fiber columns.
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Hussein, M., Kato, T., Sugiura, T. et al. Effect of Hemoperfusion Using Polymyxin B-Immobilized Fiber on IL-6, HMGB-1, and IFN Gamma in a Neonatal Sepsis Model. Pediatr Res 58, 309–314 (2005). https://doi.org/10.1203/01.PDR.0000169995.25333.F7
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DOI: https://doi.org/10.1203/01.PDR.0000169995.25333.F7
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