In abdominal aortic aneurysm repair, reperfusion injury occurs following the release of the aortic clamp and is mediated in part by neutrophils. Free radical and eicosanoid production occur locally in the reperfused tissue and in circulating neutrophils. This occurs faster than cytokine synthesis, which requires transcription. Neutrophils have been implicated in many types of inflammation including the local and remote effects of ischemia-reperfusion.
The recruitment of neutrophils into reperfused tissue is a self-perpetuating cycle. Oxygen radicals cause endothelial activation and the upregulation of P-selectin and other neutrophil-specific integrins [4, 5]. Activated neutrophils produce more free radicals and recruit more neutrophils. The activated complement components C3a and C5a are also potent chemotactic agents. Neutrophil presence alone, however, is often not sufficient to cause reperfusion injury. Hence, in many experimental animal models, the creation of a neutrophil-free environment does not reduce injury. How ever, complement inhibition even in the presence of neu-trophil sequestration is sufficient to limit local injury. This calls into question the actual role of neutrophils during reperfusion injury. They may play a secondary though not an unimportant role in mediating injury to the ischemic organ.
In intestinal ischemia, use of neutrophil adhesion molecule antagonists or antibodies to the endothelial counter receptor to prevent neutrophil sequestration blunted the remote lung but not the local intestinal injury. In one study, animals made neutropenic by pretreatment with anti-neutrophil antibodies before lower torso reperfusion had significantly decreased remote pulmonary and hepatic injury.
In discussing the role of oxygen radicals in reperfusion injury, paramagnetic resonance has shown that reactive oxygen species appear in tissue beds soon after an ischemic insult. The blockade of reactive oxygen radicals has produced promising preclinical experimental results. Manson et al. demonstrated enhanced skin flap survival when superoxide dismutase (SOD) was given after arterial and venous occlusion to scavenge reactive oxygen species. However, the administration of free radical scavengers after the onset of reperfusion proved ineffective.
It thus seems that the generation of oxygen radicals is likely to be a transient early event. The relationship between the generation of oxygen free radicals and complement activation is not well described. It is postulated that oxygen radicals are generated early and derived either from parenchymal cell xanthine oxidase or neutrophil NADPH. Either one could cause endothelial activation and cell injury, which might include exposure of the so-called "ischemia antigen" and the ensuing activation of the complement system. This idea is supported by in vitro cell culture studies that showed an increase in complement activation when hydrogen peroxide was added to human umbilical vein endothelial cells in a hypoxia-reoxygenation chamber. Studies have now concentrated on the role of the complement system in ischemia-reperfusion injury, which have been boosted by the development of specific complement knockout animals that make the study of the various components of the complement system possible. Reports indicate that therapeutic inhibition of complement with sCR1, C1 esterase inhibitor or monoclonal antibodies directed against specific complement components results in decreased tissue injury, improved organ function, and increased survival in different animal models of human disease [4, 6].
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.