Ruptured abdominal aortic aneurysm, a “two-hit” ischemia/reperfusion injury: Evidence from an analysis of oxidative products

Abstract

Purpose: Ruptured abdominal aortic aneurysm (RAAA) remains a lethal condition despite improvements in perioperative care. The consequences of RAAA are hypothesized to result from a combination of two ischemia/reperfusion events: hemorrhagic shock and lower torso ischemia. Ischemia/reperfusion results in tissue injury by diverse mechanisms, which include oxygen free radical–mediated injury produced from activated neutrophils, xanthine oxidase, and mitochondria. Oxygen-free radicals attack membrane lipids, resulting in membrane and subsequently cellular dysfunction that contributes to postoperative organ injury/failure. The purpose of this investigation was to quantify the oxidative injury that occurs as a result of the ischemia/reperfusion events in RAAAs and elective AAAs. Methods: Blood samples were taken from 22 patients for elective AAA repair and from 14 patients for RAAA repair during the perioperative period. Plasma F 2 -isoprostanes were extracted, purified, and measured with an enzyme immunoassay. Aldehydes and acyloins were purified and quantified. Neutrophil oxidative burst was measured in response to a receptor independent stimulus (phorbol 12-myristate 13-acetate) with luminol-based chemiluminescence. Results: Plasma from patients with RAAAs showed significantly elevated F 2 -isoprostane levels on arrival at hospital and were significantly elevated as compared with the levels of patients for elective repair throughout the perioperative period (two-way analysis of variance, P < .0001). Multiple regression showed a significant relationship between the phagocyte oxidative activity and F 2 -isoprostane levels ( P < .013). Total acyloin levels were significantly higher in patients with RAAAs as compared with the levels in elective cases. Conclusion: The F 2 -isoprostane levels, specific markers of lipid peroxidation, showed that patients with RAAAs had two phases of oxidative injury: before arrival at hospital and after surgery. The significant relationship between the postoperative increases in F 2 -isoprostane levels and the neutrophil oxidant production implicates neutrophils in the oxidative injury that occurs after RAAA. New therapeutic interventions that attenuate neutrophil-mediated oxidant injury during reperfusion may decrease organ failure and ultimately mortality in patients with RAAAs. (J Vasc Surg 1999;30:219-28.)