DIRECT EFFECTS OF ACUTE ADMINISTRATION OF 3,5,3'-TRIIODO-L-THYRONINE ON MYOCYTE FUNCTION

Recent studies have suggested that acute administration of 3, 5, 3' triiodo-L-thyronine (T-3) may increase ventricular performance; however, the direct cellular effects of acute T-3 administration are not understood. The objectives of this study were to determine (1) whether T-3 acts directly on the cardiac muscle cell (myocyte) itself, and (2) whether T-3 acts independently of the myocyte beta-adrenergic receptor. Accordingly, isolated myocyte function was examined using video-microscopy in normal porcine myocytes (n = 60) in the control state and in the presence of increasing T-3 concentrations (10 to 500 pmol/L). T-3 caused myocyte shortening extent, shortening velocity, and lengthening velocity to increase in a dose-dependent manner. For example, shortening velocity increased from 49.2 +/- 4.3 mu m/s at baseline to 66.5 +/- 6.1 mu m/s with 100 pmol/L T-3 (p < 0.05). beta-Adrenergic stimulation with 25 nmol/L isoproterenol increased shortening velocity to 97.6 +/- 5.7 mu m/s; isoproterenol with T-3 increased shortening velocity further to 168.5 +/- 10.9 mu m/s. Analysis of variance revealed that this increase with T-3 was independent of and additive to the beta-adrenergic receptor system. In summary, T-3 caused a dose-dependent increase in myocyte contractile performance, and these effects were independent of and additive to beta-adrenergic receptor stimulation. Thus, acute T-3 administration may provide a novel modality to improve left ventricular contractile function independent of the beta-adrenergic receptor system.