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The isolated arterially perfused rabbit interventricular septum was used to study the relationship between flow (F) and myocardial uptake and subsequent clearance of bolus injections of 13N-labeled ammonia (13NH3). Multiple 13NH3 injections were delivered to a total of 19 septa at perfusion rates (F/g) ranging from 0.2-4.0 ml.min-1.g-1. Ten septa were studied at 37 degrees C and nine were studied at 28 degrees C to obtain uptake and clearance data at different metabolic rates. The septa were perfused without recirculation with a modified Tyrode solution. Analysis of the time-activity curves generated by the injections of 13NH3 revealed that the data was best described by three components. The first two components exhibited short clearance times (t1/2s less than 7 min) in contrast to prolonged clearance times (30-500 min) for component 3. Component 1 was consistent with a freely diffusible 13NH3 compartment. Component 3 persists and permits myocardial imaging 15 min or more after 13NH3 injection. At each perfusion rate the extraction fraction of component 3 was twice as large, and the clearance time of component 3 was twice as fast at 37 as at 28 degrees C, implying that the extraction and washout of this third component are dependent on enzymatic reactions. The total myocardial extraction into component 3 from a systemic injection is determined by multiplying the extraction fraction by the perfusion rate (EF(3) X F/g) and was directly related to the perfusion rate at both 28 and 37 degrees C.

The isolated arterial perfused rabbit interventricular septum was used to measure myocardial metabolic rate for glucose (MMRGlc) and rate constants and lumped constant (LC) for the glucose analogue (/sup 18/F)fluorodeoxyglucose (FDG) using a tracer kinetic model. FDG was delivered by constant infusion during coincidence counting of tissue /sup 18/F radioactivity. The MMRGlc was measured by the Fick method. Control septa were paced at 72 beats/min and perfused at 1.5 ml/min with oxygenated perfusate containing 5.6 mM glucose and 5 mU/ml insulin. The following conditions were tested: 3.0 and 4.5 ml/min; insulin increased to 25 mU/ml; insulin omitted; 2.8 mM and 11.2 mM glucose; 144 beats/min and 96 paired stimuli/min; and anoxia. Under all conditions studied the phosphorylation (hexokinase) reaction was rate limiting relative to transport. Compared with control conditions, the phosphorylation rate constant was significantly increased with 2.8 mM glucose as well as in anoxia. With 4.5 ml/min and 11.2 mM glucose, conditions that should increase glucose flux into tissue without increasing demand, the phosphorylation rate constant decreased significantly. With 11.2 mM glucose, 96 paired stimuli/min, and anoxia without insulin, a significant increase in the hydrolysis rate of FDG 6-phosphate was observed and suggests that hydrolysis is also an importantmore » mechanism for regulating the MMRGlc. Increased transport rate constants were observed with increased flow rates, 96 paired stimuli/min, and anoxia at 96 beats/min. The LC was not significantly different from control in 11 of 14 conditions studied. Therefore, under most conditions in average LC can be used to calculate MMRGlc estimates.« less