Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction.

It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium. Here, we further explored whether this effect can be preserved in the presence of co-morbidities such as diabetes which accelerates cardiac remodeling and increases mortality after myocardial infarction. Acute myocardial infarction (AMI) was induced by left coronary ligation in rats with type I diabetes (DM) induced by streptozotocin administration (STZ; 35 mg/kg; i.p.) while sham-operated animals served as controls (SHAM). AMI resulted in distinct changes in cardiac function and geometry; EF% was significantly decreased in DM-AMI [37.9 ± 2.0 vs. 74.5 ± 2.1 in DM-SHAM]. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, wall tension index [WTI, the ratio of (Left Ventricular Internal Diameter at diastole)/2*(Posterior Wall thickness)], an index of wall stress, was found to be significantly increased in DM-AMI; 2.27 ± 0.08 versus 1.70 ± 0.05. 2D-Strain echocardiographic analysis showed reduced systolic radial strain in all segments, indicating increased loss of cardiac myocytes in the infarct related area and less compensatory hypertrophy in the viable segments. This response was accompanied by a marked decrease in the expression of TRα1 and TRß1 receptors in the diabetic myocardium without changes in circulating T3 and T4. Accordingly, the expression of TH target genes related to cardiac contractility was altered; ß-MHC and PKCα were significantly increased. TH (L-T4 and L-T3) administration prevented these changes and resulted in increased EF%, normal wall stress and increased systolic radial strain in all myocardial segments. Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics.

Thyroid hormone improves postischaemic recovery of function while limiting apoptosis: a new therapeutic approach to support hemodynamics in the setting of ischaemia-reperfusion?

Although it has long been recognized that thyroid hormone is an effective positive inotrope, its efficacy in supporting hemodynamics in the acute setting of ischaemia and reperfusion (R) without worsening reperfusion injury remains largely unknown. Thus, we investigated the effects of triiodothyronine (T3) on reperfusion injury in a Langendorff-perfused rat heart model of 30 min zero-flow ischaemia and 60 min of (R) with or without T3 (40 microg/l) at R, T3-R60, n = 11 and CNT-R60, n = 10, respectively. Furthermore, phosphorylated levels of intracellular kinases were measured at 5, 15 and 60 min of R. T3 markedly improved postischaemic recovery of left ventricular developed pressure (LVDP%); 56.0% (SEM, 4.4) in T3-R60 versus 38.8% (3.1) in CNT-R60, P < 0.05. Furthermore, LDH release was significantly lower in T3-R60. Apoptosis detection by fluorescent probe optical imaging showed increased fluorescent signal in CNT-R60 hearts, while the signal was hardly detectable in T3-R60 hearts. Similarly, caspase-3 activity was found to be 78.2 (8.2) in CNT-R60 vs 40.5 (7.1) in T3-R60 hearts, P < 0.05. This response was associated with significantly lower levels of phospho-p38 MAPK at any time point of R. No significant changes in phospho- ERK1/2 and JNK levels were observed between groups. Phospho-Akt levels were significantly lower in T3 treated group at 5 min and no change in phospho-Akt levels were observed at 15 and 60 min between groups. In conclusion, T3 administration at reperfusion can improve postischaemic recovery of function while limiting apoptosis. This may constitute a paradigm of a positive inotropic agent with anti-apoptotic action suitable for supporting hemodynamics in the clinical setting of ischaemia-reperfusion.

Thyroid hormones alterations during acute liver failure: possible underlying mechanisms and consequences.

Thyroid hormones are now recognized to change in different disease states with important consequences on severity and prognosis of disease. However, little is known about thyroid hormones' alterations in acute liver failure (ALF). To study the changes in thyroid hormones and cardiac thyroid receptors during ALF, we subjected seven female pigs to surgical liver devascularization. Liver function biochemical markers, thyroid hormones, endogenous opioids, malondialdehyde (MDA), and interleukins 1 and 6 were measured in serum for 24 h postoperatively. Heart biopsies were harvested at the end of the experiment. Baseline heart biopsies were taken from five additional animals. Serum thyroxin (T(4)) and triiodothyronine (T(3)) levels markedly decreased, whereas free-triiodothyronine and thyroxin-stimulating hormone levels did not change. T(4) and T(3) levels correlated with the degree of liver failure and with MDA and interleukin-6 levels. Beta-endorphin levels initially increased, whereas levels of leucine-enkephalin did not change. Thyroid hormone receptor-alpha1 protein expression in the heart decreased 1.6-fold after ALF, whereas myocardial myosin isoform expression remained unchanged. The downregulation of T(4) and T(3) levels during ALF seems to correlate well with the severity of disease. This downregulation related to inflammation and oxidative stress and resulted in changes in myocardial thyroid receptors.