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

Abstract

13N ammonia was characterized as a myocardial blood flow imaging agent suitable for positron-emission computed tomography. The mechanisms of uptake and retention of this agent in myocardium are not known, and effects of altered metabolism were not considered. The uptake and retention of N13 ammonia were studied in myocardium under various hemodynamic and metabolic conditions in open-chest dogs. 13N 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 1st capillary transit extraction fraction (E) of 13N ammonia averaged 0.82 .+-. 0.06 and it fell with higher flows. Myocardial 13N tissue clearance half-times were inversely related to blood flow, and ranged from 110-642 min. 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 were associated with a fall in E. Inhibition of glutamine synthetase with L-methionine sulfoximine impaired metabolic trapping of 13N ammonia and implicates the glutamic acid-glutamine reaction as the primary mechanism for ammonia fixation. The product of E times flow predicts the myocardial 13N tissue concentrations, which increased by 70% when flow was doubled. Blood flow and metabolic trapping are the primary determinants of myocardial uptake and retention of 13N ammonia. The relative constancy of metabolic trapping over a wide range of hemodynamic and metabolic conditions demononstrates the value of 13N ammonia as a myocardial blood flow imaging agent.