title: Differential effects of lower limb revascularisation on organ injury and the role of the amino acid taurine.
abstract: Lower torso revascularisation following ischaemia results in a systemic inflammatory response. Endothelial barrier function is disrupted by neutrophil-derived proteases and oxidants. Taurine, an amino acid found in large quantities in neutrophils, is a powerful endogeneous anti-oxidant. The aims of this study were to investigate the systemic effects of reperfusion following lower limb revascularisation and to evaluate the role of taurine administration in preventing this injury. A rat model of aortic occlusion (30 min) followed by 2 h of reperfusion was used. Animals were randomised to one of three groups (n = 10 per group): control; ischaemia reperfusion untreated (IR) and taurine-treated. Taurine (4% solution) was administrated orally for 48 h prior to the experiment. Neutrophil infiltration and microvascular permeability were assessed by measuring tissue myeloperoxidase activity and wet/dry weights respectively in lung, liver, kidney, and in cardiac and skeletal muscle. Statistical analysis was by means of analysis of variance (ANOVA). Reperfusion resulted in pulmonary and renal microvascular injury as assessed by organ oedema. Hepatic tissue, skeletal and cardiac muscle were unaffected by lower limb revascularisation. Taurine was effective in preventing neutrophil-mediated pulmonary but not renal microvascular injury. These data suggest that, whilst reperfusion-induced pulmonary injury is predominantly neutrophil-mediated, agents other than neutrophil-derived oxidative metabolites, capable of independently causing organ injury through direct endothelial damage, are produced during reperfusion.
authors.affiliation: Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
authors.forename: M C
authors.initials: MC
authors.lastname: Barry
authors.forename: C J
authors.initials: CJ
authors.lastname: Kelly
authors.forename: H
authors.initials: H
authors.lastname: Abdih
authors.forename: R W
authors.initials: RW
authors.lastname: Watson
authors.forename: P
authors.initials: P
authors.lastname: Stapleton
authors.forename: S J
authors.initials: SJ
authors.lastname: Sheehan
authors.forename: H P
authors.initials: HP
authors.lastname: Redmond
authors.forename: D B
authors.initials: DB
authors.lastname: Hayes
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D006614:Hindlimb / Q000098:blood supply*; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D009929:Organ Size; D009195:Peroxidase / Q000032:analysis; D011506:Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016897:Respiratory Burst; D013654:Taurine / Q000502:physiology / Q000627:therapeutic use*; D014656:Vascular Surgical Procedures
chemical_list: D011506:Proteins; D013654:Taurine; D009195:Peroxidase