Although it is recognised that prolonged ischaemia results in tissue and organ damage, the concept of reperfusion-induced tissue injury, defined as tissue damage occurring as a direct consequence of revascularisation, is relatively recent. Such events may increase the morbidity and mortality of patients undergoing vascular reconstruction, trauma surgery and transplantation. A clear understanding of the factors responsible for its development is therefore vital if protocols that reduce its impact are to be developed.

During postischaemic revascularization neutrophil-endothelial adhesion in the skeletal muscle microcirculation, promoted by the neutrophil adhesion molecule Mac-1, may impair muscle blood flow and release oxygen free radicals and proteolytic enzymes which causes further tissue injury. This study has assessed the effect of an anti-Mac-1 monoclonal antibody on the severity of skeletal muscle injury in a rat model of 6-h hindlimb ischaemia and 4-h reperfusion. In control animals a sustained impairment of muscle perfusion was associated with neutrophil sequestration, muscle infarction and muscle oedema (P < 0.001 versus normal rats). In contrast, intravenous administration of anti-Mac-1 monoclonal antibody before revascularization prevented neutrophil recruitment, reduced muscle necrosis and improved postischaemic muscle perfusion at 120 and 240 min (not significantly different from normal), thus confirming that neutrophils are important cellular mediators of skeletal muscle reperfusion injury. Monoclonal antibodies targeting neutrophil adhesion molecules may, therefore, have a role in the prevention of this complication of limb revascularization.

Patients with renal artery stenosis and peripheral vascular disease had a poor prognosis, but this was not directly attributable to renal failure.

During postischaemic revascularization neutrophil-endothelial adhesion in the skeletal muscle microcirculation, promoted by the neutrophil adhesion molecule Mac-1, may impair muscle blood flow and release oxygen free radicals and proteolytic enzymes which causes further tissue injury. This study has assessed the effect of an anti-Mac-1 monoclonal antibody on the severity of skeletal muscle injury in a rat model of 6-h hindlimb ischaemia and 4-h reperfusion. In control animals a sustained impairment of muscle perfusion was associated with neutrophil sequestration, muscle infarction and muscle oedema (P < 0.001 versus normal rats). In contrast, intravenous administration of anti-Mac-1 monoclonal antibody before revascularization prevented neutrophil recruitment, reduced muscle necrosis and improved postischaemic muscle perfusion at 120 and 240 min (not significantly different from normal), thus confirming that neutrophils are important cellular mediators of skeletal muscle reperfusion injury. Monoclonal antibodies targeting neutrophil adhesion molecules may, therefore, have a role in the prevention of this complication of limb revascularization.

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