OBJECTIVE: A decrease in plasma T3 concentration is a frequent finding in 
patients with heart failure. However, the role of this 'low T3 syndrome' on 
disease evolution has never been clarified. As phenotypic and functional 
cardiomyocyte impairments are alterations that correlate with the failing 
myocardium, we studied the long-term effects of T3 deprivation on human 
cardiomyocyte structure and calcium handling.
METHODS: Atrial cardiomyocytes and myocardial tissue were cultured with or 
without 3 nM T3. Microscopical examination of structural features was followed 
by analysis of alpha-sarcomeric actinin and sarcoplasmic reticulum calcium 
ATP-ase (SERCA-2) content. Calcium handling was studied by [Ca2+](i) imaging.
RESULTS: When stimulated with cyclopiazonic acid, a SERCA-2 inhibitor, 
T3-deprived cardiomyocytes showed significantly faster (P=0.03) and more 
transient (P=0.04) increases in [Ca(2+)](i) than T3-supplemented cells. 
Moreover, in the T3-free cultures a significantly lower number of cells 
(P=0.003) responded to caffeine, a typical activator of sarcoplasmic reticulum 
Ca(2+)-release channel. T3-deprived cardiomyocytes also presented altered 
morphology with larger dimensions than T3-supplemented cells (P < 0.0001). 
Additionally, in T3-deprived samples alpha-sarcomeric actinin and SERCA-2 
protein levels were reduced to 65.6 +/- 3% (P < 0.0001) and 74.1 +/- 4% 
(P=0.005), respectively, when compared with the T3-supplemented group.
CONCLUSIONS: Our data show that human cardiomyocyte calcium handling and 
phenotype are strongly influenced by T3 suggesting important implications of the 
'low T3 syndrome' on the progression of heart failure.