541 IMPAIRED NEUTROPHIL PHAGOCYTIC CAPACITY IN PATIENTS WITH ADVANCED CIRRHOSIS IS RELATED TO THE DEVELOPMENT OF AMMONIA-INDUCED NEUTROPHIL SWELLING

Abstract

Background and Aims: Hyperammonemia is considered a major causative factor for the development of hepatic encephalopathy, HE, in liver disease. Tissue specific ammonia metabolism in e.g. brain, liver and muscle can be assessed by dynamic Nammonia PET based on kinetic modeling of metabolic pathways and measurements of N-ammonia and N-metabolites in arterial blood. In 1990, Rosenspire et al. (J Nucl Med 1990;31:163) introduced a solid phase extraction procedure for the fractionation of N-radioactivity in blood into N-ammonia, N-urea, Nglutamine and N-glutamate following an i.v. injection of Nammonia. However, due to the radioactive half-life for N of only 10 minutes, the procedure is not suitable for blood samples taken later than 5–7 minutes after tracer injection and the method is hence unsuitable for studies of steady-state ammonia metabolism. Methods: By modifying Rosenspire’s method, we established a method enabling analysis of up to 10 blood samples taken in the time course of a 30 min dynamic N-ammonia PET study. The modified procedure was validated by radio-HPLC and showed good reproducibility in humans examined by duplicate N-ammonia injections. Results: Blood measurements from a dynamic N-ammonia PET study showed: (1) time courses of N-ammonia fractions could be described adequately by double-exponential functions; (2) wholebody clearance of N-ammonia to N-metabolites was in the order: healthy subjects (n = 5) > cirrhotic patients without HE (n =7) > cirrhotic patients with overt HE (n =8); (3) kinetics of initial tracer distribution can be assessed by using total Nconcentration in blood as input function, whereas assessment of parameters for metabolic processes (i.e. steady-state metabolism) requires determination of N-ammonia and N-metabolites. Conclusions: The study underlines the importance of using Nmetabolite-corrected blood input curves when assessing wholebody and/or organ steady-state ammonia metabolism using Nammonia PET. Patients with HE have a slower whole-body clearance of injected N-ammonia than patients without HE and healthy controls.