Force-generating preparation from human atria as a model for studying myocardial uptake of radiopharmaceuticals

The aim of this study was to assess whether an in vitro preparation of forc e-generating human atrial trabeculae driven by external electrical stimulat ion is a suitable model for determining myocardial uptake of cardiotropic r adiopharmaceuticals. Methods: Human atrial trabeculae were excised from spe cimens removed during cardiac surgery for insertion of heart-lung apparatus . Preparations were kept under physiologic conditions in a chamber continuo usly perfused by Tyrode's solution at 37 degrees C under permanent oxygenat ion. Electrical stimulation was performed at a frequency of 1 Hz. Contracti le response was continuously measured by a force transducer and registered by a lineacorder. The optimum length of the trabeculae was achieved by step wise increases of 0.1 mm muscle length. A premixed solution containing 1.92 -4.06 MBq (TI)-T-201-TICI was added to the perfusate of the chamber. After 10, 30, and 60 min, respectively, of incubation with (TI)-T-201-TICI, the a trial trabeculae were removed from the chamber and their activity was measu red by a gamma counter. These experiments were repeated with nonviable trab eculae pretreated by potassium cyanide (KCN). Myocardial uptake values were measured as cts/min, normalized to cts/min/mg, and expressed as percentage s of cts/mL/min in the perfusate (RUP). Results: Thallium uptake was found to be dependent on the functional integrity of the tissue preparations and increased over time in intact atrial trabeculae. RUP was 325% +/- 108% afte r 10 min of incubation and rose to 838% +/- 160% and 1196% +/- 493%, respec tively, at 30 and 60 min of incubation (P < 0.01). After 30 min of incubati on, RUP was significantly higher in viable than in nonviable trabeculae (83 8% +/- 160% versus 90% +/- 65%; P < 0.01). Conclusion: These preliminary re sults indicate that the model proposed is suitable for studying the mechani sms of uptake of cardiotropic radiopharmaceuticals by human myocardial tiss ue.