BACKGROUND: Left ventricular (LV) remodeling following large transmural 
myocardial infarction (MI) remains a pivotal clinical issue despite the advance 
of medical treatment over the past few decades. Identification of new 
medications to improve the remodeling process and prevent progression to heart 
failure after MI is critical. Thyroid hormones (THs) have been shown to improve 
LV function and remodeling in animals post-MI and in the human setting. However, 
changes in underlying cellular remodeling resulting from TH treatment are not 
clear.
METHODS: MI was produced in adult female Sprague-Dawley rats by ligation of the 
left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days 
sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte 
shape, arterioles, and collagen deposition in the non-infarcted area were 
measured at terminal study.
RESULTS: T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte 
cross-sectional area without further increasing myocyte length in MI rats. T4 
treatment increased the total LV tissue area by 34%, increased the non-infarcted 
tissue area by 41%, and increased the thickness of non-infarcted area by 36% in 
MI rats. However, myocyte volume accounted for only ~1/3 of the increase in 
myocyte mass in the non-infarct area, indicating the presence of more myocytes 
with treatment. T4 treatment tended to increase the total length of smaller 
arterioles (5 to 15 μm) proportional to LV weight increase and also decreased 
collagen deposition in the LV non-infarcted area. A tendency for increased 
metalloproteinase-2 (MMP-2) expression and tissue inhibitor of 
metalloproteinases (TIMPs) -1 to -4 expression was also observed in T4 treated 
MI rats.
CONCLUSIONS: These results suggest that long-term T4 treatment after MI has 
beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the 
non-infarcted area. Most importantly, results suggest improved survival of 
myocytes in the peri-infarct area.