Background:
Low thyroid hormone (TH) function is recognized as a significant contributor in the pathogenesis after acute myocardial infarction (MI). Endothelial dysfunction contributes significantly to the poor prognosis of MI. We hypothesize that long-term treatment with low dose T3 improves endothelial function and cardiac contractile activity compared to beta blocker, the current recommended therapy for MI.
Methods:
Adult female Sprague-Dawley rats were subjected to left anterior descending coronary artery ligation (MI) or sham surgeries. Survivors were randomly assigned to vehicle (MI, n=11), T3 (MI+T3, n=11) and metoprolol (MI+Meto, n=11). Vehicle, T3 (5 ug/kg/day) and metoprolol (2 mg/kg/day) were supplied in drinking water ad libitum immediately following MI for 2 months. Heart function and LV hemodynamics were measured. Isolated thoracic aortic rings were used to test relaxation response to acetylcholine (ACh) in a wire myograph. The maximal effect elicited by ACh (E
max
) and the sensitivity to ACh (pEC
50
) were analyzed. One-way ANOVA with Bonferroni correction was used for multiple comparisons.
Results:
Serum concentration of free and total T3 were normal in all the experimental groups. T3 and metoprolol improved LV contractile function measured by fractional shortening (21.88±2.06 vs 17.88±1.23%, p<0.01, T3 vs MI; 21.12±3.88 vs 17.88±1.23%, p<0.05, Meto vs MI; 46.86±1.84% for sham) and LV +d
p
/d
t
(7307±1128 vs 5479±810 mmHg/s, p<0.01, T3 vs MI; 7022±695 vs 5479±810 mmHg/s, p<0.05; Meto vs MI; 9160±1881 mmHg/s for sham). Aortas from vehicle-treated group exhibited a marked impairment of endothelial-dependent relaxation measured by pEC
50
(6.65±0.22 vs 7.19±0.16, p<0.001, MI vs Sham), which was significantly improved in the T3 treated group (6.96±0.22 vs. 6.65±0.22, p<0.01, T3 vs MI) but not in metoprolol group (6.85±0.21 versus 6.65±0.22, p=0.22, Meto vs MI). T3 and metoprolol increased maximal relaxation measured by E
max
(90.56±3.55 vs 79.50±3.98%, p<0.001, T3 vs MI; 89.81±6.75% vs 79.50±3.98%, P<0.001, Meto vs MI; 96.93±1.91% for sham).
Conclusion:
Long-term treatment with a physiological dose of T3 following MI is equally effective as metoprolol on LV function while improving endothelial function as an additional benefit.
Ventricular arrhythmias during the first year after acute myocardial infarction: influence of long-term treatment with metoprolol.
