CARDIOPROTECTIVE EFFECTS OF THERAPEUTIC T3 TREATMENT IN MYOCARDIAL INFARCTION AND ISCHEMIA REPERFUSION
A. Martin Gerdes, Ph.D, Department of Biomedical Sciences, New York Institute of Technology-College of Osteopathic Medicine, Old Westbury, USA
Background: Myocardial Infarction (MI) leads to cardiac tissue hypothyroidism, a condition that by itself can lead to heart failure (HF). Potential improvements in LV remodeling and function with a therapeutic T3 dose after MI and ischemia/reperfusion (IR) are not clear.
Objectives: We hypothesize that a safe, low-dose T3 treatment/monitoring regimen will lead to significant cardioprotection in rats following MI and 60 minute IR.
Methods: MI was produced in adult rats by LAD ligation. T3 (4-5 µg/kg/day) in drinking water was started after MI and continued for 2 months (Mo). Vehicle (V) was used in MI controls (n=16-20/group). The same 2 month treatment protocol was used for rats with IR.
Results: Infarct size was similar in MI and MI+T3 groups. D3 mRNA expression increased in MI+V (2.7-fold) and was reversed in MI+T3 (0.49-fold). MI+T3 improved ejection fraction by 51% at 1 Mo and by 47% at 2 Mo post-MI as assessed by magnetic resonance imaging (MRI). Mean MRI wall thickness was increased at both latter time-points. Histologically, non-infarct area and wall thickness increased significantly (30% and 18% respectively). Non-infarct length was also increased. Remarkably, following MI, the incidence of atrial tachyarrhythmias that persisted following discontinuation of experimental atrial tachypacing was significantly diminished by 63% with T3. T3 did not affect heart rate. The T3 dose led to feedback inhibition of Thyroid-Stimulating Hormone (TSH) but no significant change in serum T3. T3 treatment for 2 months after IR also led to an increase in viable myocardium and improvement in LF function.
Conclusion: Results demonstrate a safe and effective post-MI and IR T3 treatment strategy that dramatically improves LV function, atrial arrhythmogenesis, non-infarct tissue remodeling, and myocyte survival with no adverse effects. This study describes an effective, translatable, treatment/monitoring protocol for T3 treatment of MI and IR.