Abstract P247: Triiodothyronine Ameliorates Endothelial Dysfunction in Rats Following Acute Myocardial Infarction

Abstract

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.