N-13 ammonia as an indicator of myocardial blood flow

SUMMARY We have characterized N-13 ammonia as a myocardial blood flow imaging agent suitable for positron-emission computed tomography. However, the mechanisms of uptake and retention of this agent in myocardium are not known, and effects of altered metabolism were not considered. Therefore, we studied the uptake and retention of N-13 ammonia in myocardium under various hemodynamic and metabolic conditions in open-chest dogs. N-13 ammonia was extracted nearly 100% during its initial capillary transit, followed by metabolic trapping that competed with flow-dependent back diffusion. At control flows, the first capillary transit extraction fraction (E) of N-13 ammonia averaged 0.82 ± 0.06. It fell with higher flows by E = 1 − 0.607 exp − 125/F. Myocardial N-13 tissue clearance half-times were similarly inversely related to blood flow, and ranged from 110–642 minutes. Cardiac work and changes in the myocardial inotropic state induced by isoproterenol and propranolol did not affect E or the tissue clearance half-times. Low plasma pH reduced E by an average of 20%, while elevated plasma pH had no effect. Decreases in flow below control also were associated with a fall in E. Inhibition of glutamine synthetase with L-methionine sulfoximine impaired metabolic trapping of N-13 ammonia and implicates the glutamic acid-glutamine reaction as the primary mechanism for ammonia fixation. The product of E times flow predicts the myocardial N-13 tissue concentrations, which increased by 70% when flow was doubled. Thus, blood flow and metabolic trapping are the primary determinants of myocardial uptake and retention of N-13 ammonia. The relative constancy of metabolic trapping over a wide range of hemodynamic and metabolic conditions demonstrates the value of N-13 ammonia as a myocardial blood flow imaging agent.