Factors which affect cerebral uptake and retention of 13NH3.

Abstract

SUMMARYThe single pass extraction of ammonia (E) by cerebral capillaries was studied in vivo in rhesus monkeys with 1S N. The value of E for 13 N-ammonia was found to be less than 100%, inversely related to cerebral blood flow and to be limited by the permeability of the blood brain barrier for ammonia. A value of the permeability surface area product was determined to be 0.0040 cm 3 /sec/gm. The single pass extraction fraction, E, for 13 N-ammonia was found to be independent of arterial blood pH (in the range of 7.2 to 7.6) and of arterial blood ammonia concentration (in the range of 80-1400 ngms/100 ml). An insulin induced hypoglycemic reduction in the cerebral metabolic rate for glucose and oxygen of 54% produced a reduction in E of about 24%. When a condition of elevated arterial blood ammonia was added to hypoglycemia, the value of E and cerebral metabolic rate for oxygen remained low while the cerebral metabolic rate for glucose increased by a factor of 2.2 indicating the presence of a detoxification shunt for ammonia. Positron tomographic images of the equilibrium cross section distribution of 13 N-ammonia appeared to reflect regional differences in variations of capillary density that are found in the cerebral tissue.

Tracer-Kinetic Models for Measuring Cerebral Blood Flow Using Externally Detected Radiotracers

“…In spite of the steady-state assumption central to the derivation of 59, Eichling et al (1974) , Raichle et al (1976), Phelps et al (1977), Raichle and Larson (1981), and others have not hesitated to use it to interpret their residue-detection data from dy namic experiments in which the tracer steady state never prevails. Justification for this can be based partly on criteria developed by Bassingthwaighte (1974) , who tested the validity of 59 for outflow-de tection experiments against simulations using a more general distributed-parameter unit-capillary model.…”

N-13 ammonia as an indicator of myocardial blood flow.

“…The singlepass extraction fraction (E) was determined by extrapolating the slope of the residue function C back to the time of peak activity and dividing the value at the intercept R' by the peak activity A. The values obtained for E were always related to the flow at the time of the bolus administration of N-13 ammonia, which frequently caused a transient, less-than-10% increase in flow not more than [5][6][7] seconds long. The myocardial half-times were calculated from the slopes of phases C and B (for phase B after the contribution of phase C had been peeled off).…”

Cerebral extraction of N-13 ammonia: its dependence on cerebral blood flow and capillary permeability -- surface area product.

“…However, the rate of exchange between the 2 species is so rapid (1.9 X 10" 5 sec to establish equilibrium), that it is unlikely that this exchange is the rate limiting step and "NH, that diffuses out of the plasma can be continuously replenished by the conversion of "NH**. 5 The permeability of 1S NH 3 through the BBB is probably largely determined by its limited lipid solubility. 6 Raichle et al" have shown an excellent correlation between lipid solubility and the BBB permeability of various alcohols which is consistent with the lipid solubility dependence reported by Pappenheimer."…”

“…Phelps et al 5 used a combination of intracarotid and intravenous injections of "NH,, and a vascular tracer to determine the unidirectional transport of "NH, and assess the amount of back diffusion. It was concluded that the size of the extravascular space for U NH, diffusion and the rapid incorporation of "NH, into amino acids normally prevents significant back diffusion.…”