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Force-Generating Preparation from Human Atria as a Model for Studying Myocardial Uptake of Radiopharmaceuticals

Nuklearmedizinische Klinik mit Poliklinik, Friedrich-Alexander-Universität, Erlangen-Nürnberg
Institut für Molekulare Biophysik, Radiopharmazie und Nuklearmedizin and Klinik fur Thorax und Kardiovaskularchirurgie, Henz und Diabeteszentrum Nordrhein-Westfalen, Bad Oeynhausen
Universitätsklinik der Ruhr-Universität, Bochum
Medizinische Universitätsklinik, Abteilung Innere Medizin III, Kardiologie und Angiologie, Albert-Ludwigs Universität, Freiburg, Germany

Correspondence: For correspondence or reprints contact: Stefan Mruck, MD, Nuklearmedizinische Klinik mit Poliklinik der Friedrich-Alexander-Univetsität Erlangen-Nümberg, Krankenhausstraße 12, D-91054 Ertangen, Germany.

ABSTRACT

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. Methods: 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°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 ²⁰¹Tl-TICI was added to the perfusate of the chamber. After 10, 30, and 60 min, respectively, of incubation with ²⁰¹Tl-TICI, the atrial trabeculae were removed from the chamber and their activity was measured by a 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). 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% 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). Conclusion: These preliminary results indicate that the model proposed is suitable for studying the mechanisms of uptake of cardiotropic radiopharmaceuticals by human myocardial tissue.

Key Words: ²⁰¹Tl • cardiotropic radiopharmaceuticals • in vitro models • myocardial trabeculae • Steiert organ bath