P‐selectin deficiency is protective against remote organ injury in a model of ruptured abdominal aortic aneurysm

Background: Multisystem organ failure (MSOF) accounts for 50–60 per cent of postoperative deaths following repair of ruptured abdominal aortic aneurysm (AAA). A murine model is described in which the combined insults of hypotension and aortic clamping reproduce the physiological changes during repair of ruptured AAA. The resulting remote organ injury (the hallmark of MSOF) is prevented in the absence of the adhesion molecule P‐selectin, which mediates neutrophil–endothelial interaction. Methods: C57BL6 wild‐type mice ( n = 4) and mice constitutively unable to express P‐selectin (P –/– ) ( n = 4) were subjected to 60 min of controlled hypotension followed by cross‐clamping of the infrarenal aorta for 60 min, reinfusion of shed blood and then 60 min of reperfusion. Controls ( n = 16) were sham‐operated, had hypotension only or clamp/reperfusion only. Lungs and kidneys were harvested and assayed for the neutrophil‐specific marker myeloperoxidase (MPO), which indicates inflammatory infiltrate in the tissue. Results: MPO levels in the organs of C57BL6 mice subjected to hypotension and aortic clamping were 50 times greater than those in sham‐operated mice. MPO levels in sham‐operated P –/– animals were similar to those in sham‐operated C57BL6 mice. MPO levels in the lungs and kidneys of P –/– mice subjected to hypotension and aortic clamping were unchanged from those in sham‐operated P –/– mice. Conclusion: The combined effects of hypotension and infrarenal aortic clamping, followed by reperfusion, are synergistic. This gives rise to a profound early inflammatory reaction in tissues remote from the site of ischaemia–reperfusion, which is likely to contribute towards clinical MSOF after ruptured AAA repair. Absence of the adhesion molecule P‐selectin protects against this remote organ injury. © 2001 British Journal of Surgery Society Ltd