Aim: 

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). We tested the hypothesis that early and sustained normalization of L-T3 serum levels after MI exerts myocardial protective effects through a mitochondria ATP-sensitive K+ channel

(MitoKATP) pathway.

Methods and results: 

Seventy-two hours after MI induced by left coronary artery ligation, rats were infused with synthetic L-T3 (1.2 mg/kg/day) or saline over 4 weeks.

Compared to saline, L-T3 infusion restored FT3 serum levels at euthyroid state (6.5±0.5 vs 4.6± 0.3 pmol/L), improved LV ejection fraction (39.5±2.5 vs 65.5±6.9%), preserved LV end-systolic wall thickening in the peri-infarct zone (6.34±3.1 vs 33.7±6.21%) and reduced LV infarct 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, LT3 significantly increased the expression of factors involved in mitochondrial DNA transcription and biogenesis, such as HIF-1_, mtTFA and PGC-1_, in the LV peri-infarct zone. To further explore mechanisms of L-T3 protective effects, we exposed isolated neonatal cardiomyocytes to H2O2 and found that L-T3 protected against cell death via a mitoKATPdependent pathway.

Conclusion: 

Early and sustained restoration of circulating LT3 after MI halves infarct size and contrasts the progression towards heart failure. This beneficial effect is likely due to enhanced capillary formation and mitochondrial protection.