The significance of the NH3-NH+(4) equilibrium on the passage of 13N-ammonia from blood to brain. A new regional residue detection model.

Abstract

The movement of 13N-labeled ammonia from blood to brain in vivo was studied in adult rhesus monkeys. The behavior of the tracer was monitored by external detection of the 511-keV annihilation-radiation photons of N-13 following rapid bolus injection into the internal carotid artery. A diffusion limitation for the transport of ammonia from blood to brain was revealed. This was attributed to the low permeability of the blood-brain barrier for the ammonium cation, e.g., at a measured cerebral blood flow of 51 (ml/min)/hg (hectogram), only 35% of the injected tracer left the vasculature and was incorporated into brain tissue. This extracted fraction not only decreased with increasing cerebral blood flow, but was influenced by the pH of the blood perfusing the brain and by the integrity of the blood-brain barrier. The data was interpreted on the basis of a new regional model of the cerebral circulation that considers both capillary heterogeneity within an external detector spatial-resolution element and the effects of shifts in the degree of ionization of vascular radioammonia due to the existence of pH gradients along the direction of flow in capillary blood. Estimates for the individual permeability coefficient-specific surface-area products were obtained for diffusive transport across the blood-brain barrier of the 2 aqueous solution ammonia species, NH3 and NH4+. These estimates are discussed.