Document Detail

Leukotrienes but not complement mediate limb ischemia-induced lung injury.
MedLine Citation:
PMID:  2539063     Owner:  NLM     Status:  MEDLINE    
Reperfusion after limb ischemia leads to sequestration of polymorphonuclear leukocytes (PMN) in the lungs and to leukocyte- (WBC) and thromboxane- (Tx) dependent respiratory dysfunction. This study examines the intermediary role of the chemoattractants leukotriene (LT)B4 and complement (C) fragments. Anesthetized sheep with chronic lung lymph fistulae underwent 2 hours of tourniquet ischemia of both hind limbs. In untreated controls (n = 7), 1 minute after tourniquet release, mean pulmonary artery pressure (MPAP) rose from 13 to 38 mmHg (p less than 0.05) and returned to baseline within 30 minutes. Pulmonary artery wedge pressure was unchanged from 3.6 mmHg. There were increases in plasma LTB4 levels from 2.46 to 9.34 ng/ml (p less than 0.01), plasma TxB2 levels from 211 to 735 pg/ml (p less than 0.05), and lung lymph TxB2 from 400 to 1005 pg/ml (p less than 0.05). C3 levels were 96% of baseline values. Thirty minutes after reperfusion, lung lymph flow (QL) increased from 4.3 to 8.3 ml/30 minutes (p less than 0.05), lymph/plasma protein ratio was unchanged from 0.6, and the lymph protein clearance increased from 2.6 to 4.6 ml/30 minutes (p less than 0.05), data consistent with increased microvascular permeability. WBC count fell within the first hour from 6853 to 3793/mm3 (p less than 0.01). Lung histology showed leukosequestration, 62 PMN/10 high-power fields (HPF) and proteinaceous exudates. In contrast to this untreated ischemic group, animals treated with the lypoxygenase inhibitor diethylcarbamazine (n = 5) demonstrated a blunted reperfusion-induced rise in MPAP to 17 mmHg (p less than 0.05). There were no increases in LTB4, TxB2, QL or lymph protein clearance (p less than 0.05). WBC count was unchanged and lung leukosequestration was reduced to 40 PMN/10 HPF (p less than 0.05). Decomplementation with cobra venom factor (n = 4) resulted in plasma C3 levels, 10% of baseline, but tourniquet release still led to pulmonary hypertension, elevated LTB4, TxB2 levels, and a decline in WBC count similar to that of untreated ischemic control animals. Histology showed 46 PMN/10 HPF sequestered in the lungs. Further, bilateral hind limb ischemia in either genetically sufficient (n = 10) or deficient (n = 10) C5 mice led to significant lung leukosequestration of 108 and 106 PMN/10 HPF, respectively, compared with 42 and 47 PMN/10 HPF in sham C5(+) and C5 (-) mice (n = 20) (p less than 0.01). These results suggest that the lung leukosequestration and increased microvascular permeability after lower torso ischemia are mediated by the chemotactic agent LTB4, but not by the complement system.
J M Klausner; I S Paterson; L Kobzik; C R Valeri; D Shepro; H B Hechtman
Related Documents :
5499033 - Effect of asphyxia due to umbilical cord occlusion in the foetal lamb on leakage of liq...
468663 - Effect of heparin or fibrinogen depletion on lung fluid balance in sheep after emboli.
181843 - Ischemic areas in perfused rat hearts: measurement by nadh fluorescence photography.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Annals of surgery     Volume:  209     ISSN:  0003-4932     ISO Abbreviation:  Ann. Surg.     Publication Date:  1989 Apr 
Date Detail:
Created Date:  1989-05-05     Completed Date:  1989-05-05     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0372354     Medline TA:  Ann Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  462-70     Citation Subset:  AIM; IM    
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Capillary Permeability
Complement System Proteins / physiology*
Hypertension, Pulmonary / etiology*,  pathology
Ischemia / complications*
Leg / blood supply*
Leukotriene B4 / physiology*
Lung / pathology
Neutrophils / pathology
Reperfusion Injury / pathology*
Grant Support
Reg. No./Substance:
71160-24-2/Leukotriene B4; 9007-36-7/Complement System Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Androgen receptor in hepatocellular carcinoma as a prognostic factor after hepatic resection.
Next Document:  Effect of perioperative blood transfusion on outcome in patients with surgically resected lung cance...