Abstract | OBJECTIVES: METHODS: In this prospective, randomized, controlled, experimental animal study, 48 male Wistar rats, weighing 300 to 350 g, were randomized to a control group ( sham) and five groups undergoing 3 hours bilateral hind limb ischemia with 2 hours reperfusion (I/R) (n = 8 per group). The control and untreated I/R groups received thaumatin, a control- protein preparation, at 2 mg/kg. Treatment groups were administered rBPI(21) intravenously at 1, 2, or 4 mg/kg body weight at the beginning of reperfusion; an additional group was administered rBPI(21) intravenously at 2 mg/kg after 1 hour of reperfusion. Plasma interleukin-6 concentration was estimated by bioassay as a measure of systemic inflammation. Plasma endotoxin concentration was determined by use of an amebocyte lysate chromogenic assay. Crossreactive immunoglobulin G and M antibodies to the highly conserved inner core region of endotoxin were measured by use of an enzyme-linked immunosorbent assay. The lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. RESULTS: I/R provoked highly significant elevation in plasma interleukin-6 concentrations (1351.20 pg/mL [860.16 - 1886.40 pg/mL]) compared with controls (125.32 pg/mL [87.76-157.52 pg/mL; P <.0001]), but treatment with rBPI(21) 2 mg/kg at onset of reperfusion (715.89 pg/mL [573.36-847.76 pg/mL]) significantly decreased interleukin-6 response compared with the nontreatment group ( P <.016). I/R increased plasma endotoxin concentrations significantly (21.52 pg/mL [6.20-48.23 pg/mL]), compared with control animals (0.90 pg/mL [0.00-2.30 pg/mL; P <.0001]), and treatment with rBPI(21) 4 mg/kg at reperfusion significantly decreased endotoxemia (1.30 pg/mL [1.20-2.20 pg/mL]), compared with the untreated group ( P <.001). The lung tissue myeloperoxidase level was significantly increased in the untreated I/R group (208.18% [128.79%-221.81%]), compared with in controls (62.00% [40.45%-80.92%; P <.0001]), and attenuated in those treated with rBPI(21) 2 mg/kg (129.54% [90.49%-145.78%; P <.05]). Data represent median and interquartile range, comparisons made with the nonparametric Mann-Whitney U test. CONCLUSIONS:
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Authors | D W Harkin, A A Barros D'Sa, M M Yassin, M Hoper, M I Halliday, T G Parks, F C Campbell |
Journal | Journal of vascular surgery
(J Vasc Surg)
Vol. 33
Issue 4
Pg. 840-6
(Apr 2001)
ISSN: 0741-5214 [Print] United States |
PMID | 11296340
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimicrobial Cationic Peptides
- Blood Proteins
- Endotoxins
- Interleukin-6
- Membrane Proteins
- Recombinant Proteins
- bactericidal permeability increasing protein
- Peroxidase
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Topics |
- Animals
- Antimicrobial Cationic Peptides
- Blood Proteins
(therapeutic use)
- Endotoxins
(blood)
- Hindlimb
(blood supply)
- Interleukin-6
(blood)
- Lung
(chemistry, pathology)
- Male
- Membrane Proteins
- Peroxidase
(analysis)
- Rats
- Rats, Wistar
- Recombinant Proteins
(therapeutic use)
- Reperfusion Injury
(blood, etiology, pathology, prevention & control)
- Systemic Inflammatory Response Syndrome
(complications)
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