Abstract-Reduction of nitrite (NO 2Ϫ ) provides a major source of nitric oxide (NO) in the circulation, especially in hypoxemic conditions. Our previous studies suggest that xanthine oxidoreductase (XOR) is an important nitrite reductase in the heart and kidney. Herein, we have demonstrated that conversion of nitrite to NO by blood vessels and RBCs was enhanced in the presence of the XOR substrate xanthine (10 mol/L) and attenuated by the XOR inhibitor allopurinol (100 mol/L) in acidic and hypoxic conditions only. Whereas endothelial nitric oxide synthase (eNOS) inhibition had no effect on vascular nitrite reductase activity, in RBCs L-NAME, L-NMMA, and L-arginine inhibited nitrite-derived NO production by Ͼ50% (PϽ0.01) at pH 7.4 and 6.8 under hypoxic conditions. Western blot and immunohistochemical analysis of RBC membranes confirmed the presence of eNOS and abundant XOR on whole RBCs. Thus, XOR and eNOS are ideally situated on the membranes of RBCs and blood vessels to generate intravascular vasodilator NO from nitrite during ischemic episodes. In addition to the proposed role of deoxyhemoglobin, our findings suggest that the nitrite reductase activity within the circulation, under hypoxic conditions (at physiological pH), is mediated by eNOS; however, as acidosis develops, a substantial role for XOR becomes evident. (Circ Res. 2008;103:957-964.)Key Words: blood vessels Ⅲ cardiovascular research Ⅲ hypoxia Ⅲ nitric oxide U ntil recently, nitrite (NO 2 Ϫ ) was considered to be merely an inactive metabolite of the pleiotropic molecule nitric oxide (NO). However, recent studies have demonstrated that this view is incorrect, and, indeed, nitrite is now believed to be an important functional vascular mediator. This functionality is thought to lie in its role as an important storage form of NO 1 that is released particularly in situations where conventional NO synthesis, via the L-arginine-NO synthase (NOS) pathway, 2 has been compromised. This reduction to NO has been implicated as underlying nitrite-induced protection against ischemia/reperfusion (I/R) and hypoxic injury in the myocardial, 3-5 hepatic, 4 renal, 6 pulmonary, 7 and cerebral vasculature. 8 More recently, the functional remit of nitrite has been extended further with the proposal that it is active in physiological conditions. Indeed, nitrite causes dosedependent vasodilatation in the brachial artery of normal volunteers, 9,10 and we have recently demonstrated that dietary nitrate, via its bioconversion to nitrite, causes a marked decrease in blood pressure, inhibition of platelet aggregation, and the prevention of endothelial dysfunction following an I/R insult in the human forearm. 11 Such findings support the thesis that nitrite may have an important role in maintaining vascular homeostasis, in addition to its protective effects against cardiovascular disease.A number of distinct endogenous pathways have been identified in facilitating reduction of nitrite to NO in the circulation, over and above that achieved by simple chemical acidification. In par...

The performance of poly-methyl pentene (PMP) oxygenators (Medos Hilite 7000LT) was compared with that of silicone membrane (SM) oxygenators (Medtronic 1-4500-2A) for adult extracorporeal membrane oxygenation (ECMO). Forty consecutive patients were selected retrospectively pre- and post-introduction of PMP oxygenators. They were selected according to the dates they received ECMO and were separated into two equal groups with similar backgrounds. The flow path resistance, gas and heat exchange efficiency, consumption of coagulation factors and platelets, blood transfusion requirements, and incidence of clots for each oxygenator type was assessed. Adult PMP oxygenators showed lower blood path resistance than SM oxygenators. However, lower consumption of blood products in these oxygenators was a direct result of their smaller surface area and heparin coated design, reducing contact activation of coagulation factors. These oxygenators are noticeably smaller, require lower priming volumes, and have better gas exchange capability than SM oxygenators. They showed greater stability and preservation of coagulation factors and platelets compared with SM oxygenators. They also had the advantage of a functioning integrated heat exchanger. Using a single PMP oxygenator in the first instance may be adequate for the majority of patients and would significantly reduce red blood cell consumption during ECMO.