Metabolic Factors and Its Implications for Quantitative Assessment of Perfusion

The residual fraction the fraction of tracer extracted and retained by the myocardium after a bolus injection of "IN-labeled ammonia (NH, " NH+) 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 [tl1⁄221 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 "IN 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 sSEM) to 1.2 ml/g/min (Res Fx = 18.4 ± 1.2%, NS). Clearance of "IN was faster because tl/2 decreased from 36 i 5 minutes to 15 : 3 minutes (p < 0.01). In 12 hearts perfused with KHRBC, Res Fx and tl/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%, tlh = 41 k 6 minutes; low flow values: Res Fx = 58.1 ± 4.4%, tl/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 ":N 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 "'N 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 perfusionm from the amount of tracer sequestered by the myocardium.