In major limb vessel trauma, reperfusion injury is increased by delayed venous reflow and prevented by antioxidant pretreatment

Background: Clinical experience of the early use of intraluminal shunts in major limb trauma at this centre aimed at restoring arterial inflow and venous outflow has been shown to reduce amputation rates and morbidity. In a model of combined arterial and venous limb vessel trauma, ischaemia–reperfusion injury caused by delayed restoration of venous drainage locally on skeletal muscle and remotely on lung was studied. Furthermore, using antioxidant pretreatment the possibility of reversing these detrimental effects was investigated. Methods: New Zealand white rabbits (n = 36) were randomized into six groups: (1) sham operation; unilateral hind limb arterial and venous occlusion for 1 h followed by (2) no reflow for 2 h; (3) arterial and venous reflow for 2 h; (4) arterial reflow alone for 2 h; (5) arterial reflow for 1 h followed by arterial and venous (delayed) reflow for a further 1 h; (6) pretreatment with an enteral combination antioxidant before combined arterial and venous occlusion with delayed venous reflow. Plasma hydroperoxide (HPO) concentration in the femoral vein was a measure of lipid peroxidation. Hindlimb skeletal muscle and lung wet-to-dry weight ratio reflected tissue oedema, and myeloperoxidase (MPO) tissue levels estimated neutrophil sequestration. Plasma glutathione peroxidase (GPx) levels in systemic vein (SV) and femoral vein effluent (FV) reflected antioxidant status. Hindlimb skeletal muscle injury was graded histologically. Results:   Femoral vein HPO (µmol l−1) GPx (units l−1) Lung MPO (units g−1) Skeletal muscle histological injury grade SV start SV end FV end Values are mean(s.e.m.). * P < 0·05 versus groups 1, 3 and 6 † P < 0·01 versus groups 1–5 ‡ P < 0·05 versus group 1 1 1·0(0·1) 414·9(31·7) 391·4(33·4) 440·1(47·2) 1·7(0·1) None 2 1·8(0·5) 291·7(10·9) 363·2(62·4) 488·6(45·6) 2·3(0·2) None 3 1·2(0·4) 423·1(68·3) 398·6(63·9) 409·1(63·9) 2·4(0·2) Mild 4 1·7(0·3) 408·8(26·4) 399·0(35·4) 397·3(26·4) 1·9(0·2) Moderate 5 2·0(0·5)* 468·0(40·8) 412·2(35·6) 358·4(22·0) 3·2(0·3)‡ Severe 6 0·9(0·2) 607·9(36·3)† 562·3(40·7)† 547·2(24·9)† 2·1(0·3) Mild Conclusion: In combined major arterial and venous vessel injury of the limb, delayed venous repair leads to significantly greater local skeletal muscle injury and remote neutrophil-mediated lung damage. Reversal of these detrimental effects with antioxidant pretreatment suggests that failure of antioxidant scavenging systems may be central to the injury accentuated by delayed venous drainage. These results support the clinical rationale for early restoration of not only arterial inflow but also venous drainage by intraluminal shunts. © 2000 British Journal of Surgery Society Ltd