116 Cardiac remodeling and failure late after myocardial infarction is exacerbated by tissue hypothyroidism

Abstract

Previous studies have shown that thyroid hormone (TH) signaling is altered after acute myocardial infarction or myocardial hypertrophy with potential physiological consequences. We investigated whether such changes are related to the severity of cardiac dysfunction. Myocardial infarction was induced in rats by coronary artery ligation (AMI), while SHAM operated animals served as controls (SHAM, n=8). Both AMI and SHAM hearts were studied after 34 weeks. AMI were divided to heart failure (AMI-HF, n=6) and non-heart failure group (AMI-NHF, n=7) as assessed by the ratio of lung weight to body weight (LGW/BW) and right ventricle weight to body weight (RV/BW). Contractile function and left ventricular (LV) remodeling was assessed by echocardiography. TRα1 was increased in both border and remote regions of viable LV of AMI-NHF (2.0 fold and 1.8 fold), while it decreased in AMI-HF (2.0 fold and 1.5 fold) vs SHAM, p<0.05. TRβ1 was reduced in border and remote regions in AMI-HF (2.8 fold and 2.0 fold) and AMI-NHF (3.6 fold and 2.0 fold) vs SHAM, p<0.05. T3 and T4 were not different between groups. Accordingly, this response corresponded to changes in cardiac function (table) and in MHC isoform expression. A marked increase in β-MHC was observed in both border and remote regions of LV of AMI-HF (76% and 75%), p<0.05 vs both SHAM and AMI-NHF while a small but significant increase in β-MHC was found in both border and remote regions of LV in AMI-NHF (62% and 60%) as compared to SHAM (48% and 50%). LGW/BW RV/BW LVEDD (mm) LVEDS (mm) EF% SHAM 3.77 (0.15) 0.35 (0.02) 6.9 (0.15) 4.0 (0.2) 75.6 (2.3) AMI-HF 3.95 (0.4) 0.43 (0.02) 8.8 (0.22) * 7.1 (0.3) * 41.2 (2.6) AMI-NHF 6.90 (0.8) ** 0.82 (0.1) ** 10.4 (0.50) ** 9.2 (0.5) ** 27 (2.0) Post-infarct remodelling results in tissue hypothyroidism. The occurrence of heart failure is accompanied by distinct changes in TR and MHC isoform expression corresponding to a marked regression to the fetal pattern. * p<0.05 vs SHAM, ** p<0.05 vs SHAM and AMI-HF