Extracellular levels of adenosine increase during hypoxia. While acute increases in adenosine are important to counterbalance excessive inflammation or vascular leakage, chronically elevated adenosine levels may be toxic. Thus, we reasoned that clearance mechanisms might exist to offset deleterious influences of chronically elevated adenosine. Guided by microarray results revealing induction of endothelial adenosine deaminase (ADA) mRNA in hypoxia, we used in vitro and in vivo models of adenosine signaling, confirming induction of ADA protein and activity. Further studies in human endothelia revealed that ADA-complexing protein CD26 is coordinately induced by hypoxia, effectively localizing ADA activity at the endothelial cell surface. Moreover, ADA surface binding was effectively blocked with glycoprotein 120 (gp120) treatment, a protein known to specifically compete for ADA-CD26 binding. IntroductionPhysiologic adaptation and pathophysiologic response to hypoxia are currently areas of intense investigation, and several reports suggest that both transcriptional and metabolic pathways may contribute to a broad range of diseases. 1 For example, during episodes of hypoxia/ischemia, polymorphonuclear leukocytes (PMNs) are mobilized from the intravascular space to the interstitium, 2,3 and such responses may contribute significantly to tissue damage during subsequent reperfusion. 4 Emigration of PMNs through the endothelial barrier is associated with a disruption of tissue barriers, creating the potential for vascular fluid leakage and subsequent edema formation. 5,6 At the same time, extracellular nucleotide metabolites (particularly adenosine) may function as endogenous anti-inflammatory mediators during hypoxia. 1,3,4,6,7 Vascular adenosine signaling during hypoxia has been implicated, dampening pathophysiologic changes related to increased tissue permeability, accumulation of inflammatory cells, and transcriptional induction of proinflammatory cytokines during hypoxia. 1,8 Several lines of evidence support this assertion: first, adenosine receptors are widely expressed on vascular endothelial cells, and have been studied for their capacity to modulate inflammation; 1,3,5 second, murine models of inflammation and/or hypoxia provide evidence for adenosine receptor signaling as a mechanism for regulating hypoxia responses in vivo. Indeed, mice genetically deficient in surface enzymes necessary for adenosine generation (ecto-apyrase, CD39 [conversion of ATP to AMP] and ecto-5Ј-nucleotidase, CD73 [conversion of AMP to adenosine]) show increased hypoxia-associated tissue damage and vascular leak syndrome during hypoxia. 5,6 Third, hypoxia accompanies the normal inflammatory response [9][10][11] and is associated with significantly increased levels of adenosine. 12,13 The exact source(s) of adenosine are not well defined, but likely include a combination of increased intracellular metabolism and amplified extracellular phosphohydrolysis of adenine nucleotides via surface ectonucleotidases. 5,6 In addition, recent stud...

Procoagulant and anticoagulant factor levels were significantly lower in patients after the Fontan operation independent of hemodynamic variables peculiar to the Fontan circulation. Increased factor VIII level requires further evaluation as a cause of thrombosis in patients with Fontan physiology and may also indicate a subset of these patients in whom anticoagulation is indicated.

Background— Routine preoperative catheterization is standard practice in patients with single-ventricle physiology before bidirectional Glenn anastomosis. Because catheterization is invasive and exposes patients to ionizing radiation, cardiac magnetic resonance (CMR) may be a safe and effective alternative. Methods and Results— We conducted a prospective, randomized, single-center clinical trial comparing catheterization with CMR in patients considered for bidirectional Glenn operation from February 2003 to June 2006. End points were frequency of adverse events of the preoperative evaluation and a composite score of clinically successful surgery. Of 92 eligible patients, 82 were enrolled on the basis of screening echocardiogram, fulfillment of inclusion criteria, and informed consent. Patients were randomized to catheterization (n=41) or CMR (n=41). There were no baseline differences between groups. Four treatment crossovers occurred, 3 to catheterization and 1 to CMR. Catheter interventions were performed in 17 patients (41%). Catheterization resulted in more minor adverse events (78% versus 5%; P <0.001), longer preoperative hospital stays (median, 2 versus 1 day; P <0.001), and higher hospital charges ($34 477 versus $14 921; P <0.001). There was 1 major adverse event in the CMR group ( P =1.0). The operative course and frequency of postoperative complications were similar between the 2 groups. The proportion of patients who had a successful bidirectional Glenn operation was similar (71% versus 83%; P =0.3). At the 3-month follow-up, there were no differences in clinical status, oxygen saturation, or frequency of reinterventions. Conclusions— CMR is a safe, effective, and less costly alternative to routine catheterization in the evaluation of selected patients before bidirectional Glenn operation. Further studies are necessary to determine whether there are long-term benefits from transcatheter interventions in these patients.