Neutrophil sequestration in the lung following acute aortic occlusion starts during ischaemia and can be attenuated by tumour necrosis factor and nitric oxide blockade.
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Tassiopoulos AK, Hakim TS, Finck CM, Pedoto A, Hodell MG, Landas SK, McGraw DJ
Neutrophil sequestration in the lung following acute aortic occlusion starts during ischaemia and can be attenuated by tumour necrosis factor and nitric oxide blockade.
Eur J Vasc Endovasc Surg. 1998 Jul;16(1):36-42. doi: 10.1016/s1078-5884(98)80089-0.
- PubMed ID
- 9715714 [ View in PubMed]
- Abstract
OBJECTIVES: To investigate the role of lower extremity ischaemia in acute lung injury with special emphasis on the role of tumour necrosis factor (TNF) and nitric oxide (NO) as mediators of neutrophil (PMN) chemotaxis in the lung. DESIGN: Prospective randomised study. MATERIALS AND METHODS: Sprague-Dawley rats were randomized into four groups: group 1 (x-clmap): aorta clamped just above the bifurcation for 3 h; group 2 (AG): 50 mg/kg aminoguanidine, a specific inducible NO synthase (iNOS) inhibitor, was administered prior to aortic occlusion; group 3 (Steroids): 1 mg/kg dexamethasone was administered prior to aortic occlusion; and group 4 (TNFbp): 2 mg/kg TNFbp, a PEGylated dimeric form of the high affinity TNF receptor I (R1) was administered prior to aortic occlusion to block TNF action. Groups 2, 3 and 4 were subjected to the same ischaemia time as group 1. NO concentration in the exhaled gas (ENO) was measured in 30 min intervals. At the end of the 3 h ischaemia, one lung was excised and fixed for routine histological evaluation, and the other underwent bronchoalveolar lavage (BAL). PMN chemotaxis towards the BAL fluid was then measured using the blindwell technique. RESULTS: ENO in group 1 increased from 0.9 +/- 0.3 ppb at baseline, to 41.3 +/- 9.2 ppb at the end of ischaemia. Animals in this group exhibited significant lung inflammation. Aminoguanidine, dexamethasone and TNFbp blocked NO production (peak ENO values of 7.2 +/- 1.9, 12.6 +/- 1.3 and 8.9 +/- 1.7 ppb for groups 2, 3 and 4 respectively), decreased PMN chemotaxis and sequestration in the lung, and attenuated lung inflammation. CONCLUSIONS: Acute lung injury resulting from distal aortic occlusion starts during ischaemia. TNF and NO blockade decrease PMN chemotaxis and sequestration and attenuate the lung injury process.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Pimagedine Nitric oxide synthase, inducible Protein Humans YesInhibitorDownregulatorDetails