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 force-generating human atrial trabeculae driven by external electrical stimulation is a suitable model for determining myocardial uptake of cardiotropic radiopharmaceuticals.

Human atrial trabeculae were excised from specimens removed during cardiac surgery for insertion of heart-lung apparatus. Preparations were kept under physiologic conditions in a chamber continuously perfused by Tyrode's solution at 37 degrees C under permanent oxygenation. Electrical stimulation was performed at a frequency of 1 Hz. Contractile response was continuously measured by a force transducer and registered by a lineacorder. The optimum length of the trabeculae was achieved by stepwise increases of 0.1 mm muscle length. A premixed solution containing 1.92-4.06 MBq 201TI-TICI was added to the perfusate of the chamber. After 10, 30, and 60 min, respectively, of incubation with 201TI-TICI, the atrial trabeculae were removed from the chamber and their activity was measured by a gamma counter. These experiments were repeated with nonviable trabeculae pretreated by potassium cyanide (KCN). Myocardial uptake values were measured as cts/min, normalized to cts/min/mg, and expressed as percentages of cts/mL/min in the perfusate (RUP).

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% after 10 min of incubation and rose to 838% +/- 160% and 1196% +/- 493%, respectively, at 30 and 60 min of incubation (P < 0.01). After 30 min of incubation, RUP was significantly higher in viable than in nonviable trabeculae (838% +/- 160% versus 90% +/- 65%; P < 0.01).

These preliminary results indicate that the model proposed is suitable for studying the mechanisms of uptake of cardiotropic radiopharmaceuticals by human myocardial tissue.