The dependence of accumulation of 13NH3 by myocardium on metabolic factors and its implications for quantitative assessment of perfusion

Abstract

The residual fraction - the fraction of tracer extracted and retained by the myocardium after a bolus injection of 13N-labeled ammonia (NH3 ⇆ NH+4) - was studied in isolated perfused rabbit hearts under conditions in which flow and cardiac metabolism could be selectively and independently controlled. Residual fraction and clearance (defined as the half-time [t 1/2 ] required for elimination of sequestered tracer) of this positron-emitting tracer were monitored and quantified by coincident detection. Hearts were perfused with either modified Krebs-Henseleit buffer alone (KH) or KH enriched with washed sheep erythrocytes (KH-RBC) to augment oxygen-carrying capacity. In 13 hearts perfused with KH, the residual fraction (Res Fx) of 13N counts was not altered significantly when flow was decreased by 75% from a control rate of 4.2 ml/g/min (Res Fx = 17.9 ± 2.7%; mean ± SEM) to 1.2 ml/g/min (Res Fx = 18.4 ± 1.2%, NS). Clearance of 13N was faster because t 1/2 decreased from 36 ± 5 minutes to 15 ± 3 minutes (p <0.01). In 12 hearts perfused with KH-RBC, Res Fx and t 1/2 were not altered despite marked ischemia when flow was diminished by 75% from control flow of 1.4 to 0.3 ml/g/min (control values: Res Fx = 54.6 ± 2.4%, t 1/2 = 41 ± 6 minutes; low flow values: Res Fx = 58.1 ± 4.4%, t 1/2 = 35 ± 10 minutes, NS). In four additional hearts perfused with KH-RBC with 0.02 mg/ml of methionine sulfoximine, a glutamine synthetase inhibitor, myocardial retention of 13N counts was reduced by >60% and myocardial clearance was prolonged compared to pre-inhibition values. The results obtained indicate that the retention and clearance of 13N activity by myocardium are influenced to a considerable extent by the metabolic state of the myocardium. Accordingly, relationships between extraction and retention of tracer and flow per se are complex and preclude direct estimation of perfusion from the amount of tracer sequestered by the myocardium.