Multiple organ dysfunction syndrome: Role of xanthine oxidase and nitric oxide  Dale A Parks, Kelly A Skinner, Henry B Skinner, Sidhartha Tan  Pathophysiology  Volume 5, Issue 1, Pages 49-66 (June 1998) DOI: 10.1016/S0928-4680(98)00008-X

Fig. 1 Proposed scheme for role of XO as a circulating mediator that binds to vascular cell surface of endothelium, produces reactive oxygen species, interacts with nitric oxide (⋅NO) and directly or indirectly results in multisystem organ dysfunction. Pathophysiology 1998 5, 49-66DOI: (10.1016/S0928-4680(98)00008-X)

Fig. 2 Plasma half-life of XO. Rats were administered 125I-labeled XO and blood samples taken to determine the mean circulating half-life of XO. In control animals, the mean half-life of XO was 6±0.8 h. The administration of heparin significantly reduced XO half-life (4.0±0.5 h) suggesting that XO was displaced from GAG binding sites thereby allowing more rapid clearance. A more rapid clearance of XO from the circulation may result in less severe pathologic sequelae and reduce the remote tissue damage associated with circulating XO. Pathophysiology 1998 5, 49-66DOI: (10.1016/S0928-4680(98)00008-X)

Fig. 3 Perfusion of the isolated rat liver with 2.5 (•), 5.0 (□) or 10.0 (♦) mU/ml XO increased perfusate level of XO by ∼1, 2 and 4 mU/ml, respectively. Perfusion with inactive XO (♢) did not increase circulating XO levels. These data indicate that circulating XO can damage tissues with high intracellular XO activity, increasing circulating XO activity and thereby amplifying tissue injury. Pathophysiology 1998 5, 49-66DOI: (10.1016/S0928-4680(98)00008-X)

Fig. 4 The potential role of xanthine oxidase (XO) in generation of oxidants, formation of antioxidants and in the regulation of nitric oxide (⋅NO). Pathophysiology 1998 5, 49-66DOI: (10.1016/S0928-4680(98)00008-X)

Fig. 5 It has been demonstrated that perfusion of non-ischemic isolated heart with post-ischemic liver effluent results in significant myocardial injury (CK-MB release, upper panel) and a marked depression in myocardial function (dP/Dt, lower panel). These data indicate that circulating mediators are released into the circulation and can result in remote tissue damage. Pathophysiology 1998 5, 49-66DOI: (10.1016/S0928-4680(98)00008-X)