title: Reperfusion injury is greater with delayed restoration of venous outflow in concurrent arterial and venous limb injury.
abstract: BACKGROUND
  Complex limb trauma often involves combined arterial and venous injury, and the resultant ischaemia-reperfusion injury (IRI) causes both local and remote organ injury. This study assessed the influence of the timing of restoration of venous drainage on IRI.
  
  
  METHODS
  Male New Zealand white rabbits (n = 36) were randomized into six groups: sham operation (group 1) and unilateral hind limb arterial and venous occlusion for 1 h followed by no reflow for 2 h (group 2), arterial and venous reflow for 2 h (group 3), arterial reflow alone for 2 h (group 4), arterial reflow alone for 1 h followed by arterial and venous (delayed) reflow for a further 1 h (group 5), and pretreatment with an enteral combination antioxidant before occlusion of both artery and vein and delayed venous reflow (group 6). Plasma hydroperoxide (HPO) and glutathione peroxidase concentration, hind limb skeletal muscle and lung tissue wet : dry weight ratios and myeloperoxidase (MPO) concentration were measured.
  
  
  RESULTS
  The plasma HPO level in the femoral vein effluent was significantly greater after delayed venous reflow (mean(s.e.m.) 2. 02(0.54) micromol/l) than in control animals (0.98(0.10) micromol/l) (P < 0.05). There was also a significantly greater tissue wet : dry weight ratio after delayed venous reflow than in controls, in skeletal muscle (mean(s.e.m.) 6.89(0.14) versus 5.34(0.54); P < 0. 05) and lung (9.20(1.14) versus 7.23(0.38); P < 0.05) tissue. Lung tissue MPO activity was significantly greater after delayed venous reflow compared with controls (3.20(0.28) versus 1.86(0.14) units/g; P < 0.005), and also in comparison to simultaneous arterial and venous reflow (2.40(0.24) units/g; P < 0.05). In the antioxidant pretreatment group there was no significant increase in plasma HPO concentration, tissue MPO level or tissue wet : dry weight ratio compared with the control group.
  
  
  CONCLUSIONS
  In combined major arterial and venous injury of the limb, delayed restoration of venous drainage leads to significantly greater local skeletal muscle injury and remote neutrophil-mediated lung injury. These results support the clinical rationale for early restoration not only of arterial inflow but also venous drainage by means of intraluminal shunts.
authors.affiliation: Vascular Surgery Unit, Royal Victoria Hospital, Department of Surgery, Queen's University of Belfast and Department of Clinical Biochemistry, Royal Victoria Hospital and Queen's University of Belfast, Belfast, UK.
authors.forename: D W
authors.initials: DW
authors.lastname: Harkin
authors.forename: A A
authors.initials: AA
authors.lastname: D'Sa
authors.forename: M M
authors.initials: MM
authors.lastname: Yassin
authors.forename: I S
authors.initials: IS
authors.lastname: Young
authors.forename: J
authors.initials: J
authors.lastname: McEneny
authors.forename: D
authors.initials: D
authors.lastname: McMaster
authors.forename: M D
authors.initials: MD
authors.lastname: McCaigue
authors.forename: M I
authors.initials: MI
authors.lastname: Halliday
authors.forename: T G
authors.initials: TG
authors.lastname: Parks
mesh_terms: D000818:Animals; D003250:Constriction; D005121:Extremities / Q000098:blood supply* / Q000293:injuries / Q000601:surgery; D005263:Femoral Artery / Q000502:physiology; D005268:Femoral Vein / Q000502:physiology; D005979:Glutathione Peroxidase / Q000097:blood; D006861:Hydrogen Peroxide / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000209:etiology*; D013997:Time Factors
chemical_list: D006861:Hydrogen Peroxide; D009195:Peroxidase; D005979:Glutathione Peroxidase