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Titolo:
Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury
Autore:
Harkin, DW; DSa, AAB; McCallion, K; Hoper, M; Halliday, MI; Campbell, FC;
Indirizzi:
Queens Univ Belfast, Inst Clin Sci, Dept Surg, Belfast BT12 6BJ, Antrim, North Ireland Queens Univ Belfast Belfast Antrim North Ireland BT12 6BJ , North Ireland Royal Victoria Hosp, Vasc Surg Unit, Belfast BT12 6BA, Antrim, North Ireland Royal Victoria Hosp Belfast Antrim North Ireland BT12 6BA , North Ireland
Titolo Testata:
ANNALS OF SURGERY
fascicolo: 2, volume: 234, anno: 2001,
pagine: 233 - 244
SICI:
0003-4932(200108)234:2<233:BPASI>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
ABDOMINAL AORTIC-ANEURYSM; TUMOR-NECROSIS-FACTOR; PULMONARY MICROVASCULAR PERMEABILITY; AMINO-TERMINAL FRAGMENT; LOWER TORSO ISCHEMIA; WHOLE-BLOOD; NEUTROPHIL CHEMILUMINESCENCE; MONOCLONAL-ANTIBODY; VASCULAR-SURGERY; TRAUMA PATIENTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Harkin, DW Queens Univ Belfast, Inst Clin Sci, Dept Surg, Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland Queens Univ Belfast Grosvenor Rd Belfast Antrim North Ireland BT12 6BJ
Citazione:
D.W. Harkin et al., "Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury", ANN SURG, 234(2), 2001, pp. 233-244

Abstract

ObjectiveTo investigate the role of recombinant bactericidal/permeabillty-increasing protein (rBPI(21)) in the attenuation of the sepsis syndrome and acute lung injury associated with lower limb ischemia-reperfusion (I/R) injury. Summary Background DataGut-derived endotoxin has been implicated in the conversion of the sterileinflammatory response to a lethal sepsis syndrome after lower torso I/R injury. rBPI(21) is a novel antiendotoxin therapy with proven benefit in sepsis. MethodsAnesthetized ventilated swine underwent midline laparotomy and bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of reperfusion. Two groups (n = 6 per group) were randomized to receive, by intravenous infusion over 30 minutes, at the start of reperfusion, either thaumatin,a control-protein preparation, at 2 mg/kg body weight, or rBPI(21) at 2 mg/kg body weight. A control group (n = 6) underwent laparotomy without further treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of anesthesia. Blood from a carotid artery cannula was taken every half-hour for arterial blood gas analysis. Plasma was separated and stored at-70 degreesC for later determination of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a markers of systemic inflammation, Plasma endotoxinconcentration was measured using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. Bronchoalveolar lavage protein concentration was measured by the bicinclinoic acid method as a measure of capillary-alveolar protein leak. The alveolar-arterial gradient was measured; a large gradient indicated impaired oxygen transport and hence lung injury. ResultsBilateral hind limb I/R injury increased significantly intestinal mucosal acidosis, intestinal permeability, portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak, and impaired gas exchange. Conversely, pigs treated with rBPI(21) 2 mg/kg at the onset of reperfusion had significantly reduced intestinal mucosal acidosis, portal endotoxin concentrations, and circulating phagocytic cell priming and had significantly less pulmonary edema, leukosequestration, and respiratory failure. Conclusions Endotoxin transmigration across a hyperpermeable gut barrier, phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis, and pulmonary dysfunction. This study shows that rBPI(21) ameliorates these adverse effects and may provide a novel therapeutic approach for prevention of I/R-associated sepsis syndrome.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 06:38:11