Protective effects of a potent C5a receptor antagonist on experimental acute limb ishemia-reperfusion in rats

Woodruff, Trent M., Arumugam, Thiruma V., Shiels, Ian A., Reid, Robert C., Fairlie, David P. and Taylor, Stephen M. (2004) Protective effects of a potent C5a receptor antagonist on experimental acute limb ishemia-reperfusion in rats. Journal of Surgical Research, 116 1: 81-90. doi:10.1016/j.jss.2003.04.001


Author Woodruff, Trent M.
Arumugam, Thiruma V.
Shiels, Ian A.
Reid, Robert C.
Fairlie, David P.
Taylor, Stephen M.
Title Protective effects of a potent C5a receptor antagonist on experimental acute limb ishemia-reperfusion in rats
Journal name Journal of Surgical Research   Check publisher's open access policy
ISSN 0022-4804
1095-8673
Publication date 2004-01-01
Sub-type Article (original research)
DOI 10.1016/j.jss.2003.04.001
Volume 116
Issue 1
Start page 81
End page 90
Total pages 10
Editor D. W. McFadden
W. W. Souba
Place of publication London, U.K.
Publisher Academic Press
Language eng
Subject C1
320599 Pharmacology not elsewhere classified
730102 Immune system and allergy
1103 Clinical Sciences
Formatted abstract
Objective.
The capacity of a potent C5a receptor antagonist to inhibit various parameters of local and remote organ injury following lower limb ischemia-reperfusion (I/R) in rats was investigated.
Methods.

Rats were subjected to 2 h bilateral hindlimb ischemia and 4 h reperfusion. Drug-treated rats received AcF-[OPdChaWR] (1 mg/kg) iv either 10 min before ischemia or 10 min prior to reperfusion, or orally (10 mg/kg) 30 min prior to ischemia. Levels of circulating creatine kinase (CK), lactate dehydrogenase (LDH), alanine and aspartate aminotransferase (ALT/AST), creatinine, blood urea nitrogen (BUN), polymorphonuclear leukocytes (PMNs), and calcium (Ca++) and potassium (K+) ions were determined. Other parameters measured included urinary protein levels, muscle edema, and myeloperoxidase (MPO) concentrations in the lung, liver, and muscle along with liver homogenate tumor necrosis factor-α (TNF-α) concentrations.
Results.

Limb I/R injury was characterized by significant elevations of CK, LDH, ALT, AST, creatinine, BUN, proteinuria, PMNs, serum K+, muscle edema, organ MPO, and liver homogenate TNF-α concentrations, but a significant reduction in serum Ca2+ concentrations. When rats were treated with AcF-[OPdChaWR], there were significant improvements in all these parameters.
Conclusion.
These results indicate a pivotal role for C5a in inducing local and remote organ injury and suggest a possible new drug therapeutic category for preventing anticipated tissue injury associated with I/R.
(C) 2004 Elsevier Inc. All rights reserved.
Keyword Acute limb ischemia
Ischemia-reperfusion injury
C5a receptor antagonist
Antiinflammatory
Lower-torso ischemia
Tumor-necrosis-factor
Systemic inflammatory response
Bilateral hindlimb ischemia
Skeletal-muscle
Renal-failure
Lung Injury
Ischemia/reperfusion Injury
Organ dysfunction
Complement
Surgery
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 15:20:57 EST