Introduction:Arginase competes with nitric oxide synthase by converting Arginine (Arg) to ornithine, thereby decreasing Arg and nitric oxide bioavailability. Both enzymes are modulated by shear stress. Single ventricle (1V) physiology after Fontan palliation creates chronically low shear stress in the pulmonary arterial (PA) tree.Hypothesis:We hypothesize that a gradient exists in plasma arginase concentration (conc) & activity (act) from the right atrium(RA) to the pulmonary capillary bed (PCW) in patients with biventricular circulation (2V) & is altered in 1V physiology following Fontan palliation.Methods:A prospective cohort study in patients undergoing cardiac catheterization for ASD or PDA closure & Fontan surveillance. Blood samples were obtained in 18 1V & 11 2V patients from 4 sites: RA/Fontan, PA, PCW & systemic artery. Plasma arginase conc & act were measured & compared to 11 controls. Hemodynamic data was recorded. Repeated measures was used after rank transformation due to non-parametric distribution.Results:Median age in years for 1V was 13.5[11.1-15.2], 61% male, 11.6[9.2-14], 27% male for 2V & 9.9[4.5-12.6], 50% male for controls. Arginase conc, act & act:conc were similar in 1V/2V patients vs control. There was a rise in conc from the Fontan to PCW in 1V not 2V subjects (p=0.02). Act & act:conc were similar throughout the vasculature in 1V and 2V. PA pressure, PCW pressure, Qp & Qs were higher in 2V vs 1V, but oxygen delivery was similar. Conc in the Fontan was associated with pleural effusion post Fontan (p=0.014) & larger RPA diameter (r=0.77, p=0.001). Act in PA is inversely proportional to Qp (R2=0.42, p=0.02).Conclusions:Arginase conc increases across the lung in Fontan but not biventricular circulation. Arginase conc in the Fontan circuit is associated with effusions post Fontan & larger RPA diameter; activity predicts lower Qp. Arginase from the hepatic/lower body may be an important determinant in Fontan physiology.