258 Post-ischemic cardiac remodeling is accelerated in diabetic rats: similarities to clinical and tissue hypothyroidism

Abstract

We investigated whether postischemic cardiac remodeling (REM) is accelerated in diabetic rats with possible involvement of thyroid hormone (TH) signaling in this response. Changes in TH signaling occur during REM after acute myocardial infarction (MI) and contribute to cardiac dysfunction. Diabetes was induced in Wistar rats by streptozotocin injection (35mg/Kg i.p.). After 30 days diabetic rats (DM-AMI, n=9) were subjected to MI, while control rats were either sham-operated (SHAM, n=10) or subjected to MI (AMI(1), n=10). After 2 weeks, TRα1 and TRα1 expression and TH levels were measured. Hypothyroid rats by propyl-thiouracil administration (0.05%) in water for 3 weeks were subjected to MI (HYPO-AMI, n=6) while untreated MI rats served as controls (AMI(2), n=6). LV dimensions (LVEDD and LVEDS) and ejection fraction (EF%) were used to assess contractility and REM 2 weeks after MI using echocardiography. Cardiac function was markedly decreased in DM –AMI. Scar (mm 2 ) LVEDD (mm) LVEDS (mm) EF% SHAM ----- 6.5 (0.1) 3.8 (0.2) 76 (2.6) AMI(1) 79 (4.0) 7.7 (0.2) * 5.7 (0.2) * 52 (1.5) * DM-AMI 83 (4.9) 8.5 (0.2) ** 7.0 (0.3) ** 39 (2.1) ** * p<0.05 vs SHAM, ** p<0.05 vs SHAM and AMI(1) In AMI(1), TRα1 and TRβ1 protein expression were not changed significantly as compared to SHAM while in DM-AMI, both TRα1 and TRβ1 were decreased 1.7 and 1.9 fold respectively as compared to SHAM, p<0.05. T3 and T4 levels were not different between groups. HYPO-AMI hearts, with scar areas comparable to AMI(2) hearts [97(4.7) vs 105 (10.3), p>0.05], showed a similar unfavorable functional response : EF% was found to be markedly reduced [24 (0.9) in HYPO-AMI vs 36.2 (1.0) in AMI(2), p<0.05], while LVEDS was 8.3 (0.2) for HYPO-AMI and 7.5(0.1) for AMI(2), p<0.05. LVEDD equally increased in the 2 groups. Postischemic cardiac remodeling is accelerated both in hypothyroid and diabetic hearts. Tissue hypothyroidism which occurs in DM after myocardial infarction, may at least in part, account for this response.