3,5,3'-Levo-triiodothyronine (L-T3) is essential for DNA transcription, 
mitochondrial biogenesis and respiration, but its circulating levels rapidly 
decrease after myocardial infarction (MI). The main aim of our study was to test 
whether an early and sustained normalization of L-T3 serum levels after MI 
exerts myocardial protective effects through a mitochondrial preservation. 
Seventy-two hours after MI induced by anterior interventricular artery ligation, 
rats were infused with synthetic L-T3 (1.2 μg/kg/day) or saline over 4 weeks. 
Compared to saline, L-T3 infusion restored FT3 serum levels at euthyroid state 
(3.0 ± 0.2 versus 4.2 ± 0.3 pg/ml), improved left ventricular (LV) ejection 
fraction (39.5 ± 2.5 versus 65.5 ± 6.9%), preserved LV end-systolic wall 
thickening in the peri-infarct zone (6.34 ± 3.1 versus 33.7 ± 6.21%) and reduced 
LV infarct-scar size by approximately 50% (all P < 0.05). Moreover, L-T3 
significantly increased angiogenesis and cell survival and enhanced the 
expression of nuclear-encoded transcription factors involved in these processes. 
Finally, L-T3 significantly increased the expression of factors involved in 
mitochondrial DNA transcription and biogenesis, such as hypoxic inducible 
factor-1α, mitochondrial transcription factor A and peroxisome proliferator 
activated receptor γ coactivator-1α, in the LV peri-infarct zone. To further 
explore mechanisms of L-T3 protective effects, we exposed isolated neonatal 
cardiomyocytes to H(2)O(2) and found that L-T3 rescued mitochondrial biogenesis 
and function and protected against cell death via a mitoKATP dependent pathway. 
Early and sustained physiological restoration of circulating L-T3 levels after 
MI halves infarct scar size and prevents the progression towards heart failure. 
This beneficial effect is likely due to enhanced capillary formation and 
mitochondrial protection.