Abstract 133: Cardiovascular Protective Effect of Thyroxine and Nano- Thyroxine Against Ischemic Insults

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Introduction: Cardioprotection is a key purpose for therapeutic interventions in cardiology that aim to reduce infarct size, and thus prevent progression toward heart failure, after acute ischemic and cardiac arrest. Triiodothyronine/thyroxine (T3) therapy has been used to reverse myocardial stunning. Hyperthyroidism prevents the stunning with high dependence on the mitochondrial sodium-calcium exchanger and mitochondrial K+ channels. Hypothesis: This study aimed to investigate the positive protective role of T3 and PRO-AL 616 (Nano-T3) and PRO-AL 617 (Nano-T3 with Phosphocreatine, Pcr) in hypoxia-mediated cardiac cell insults, as well as its influences on vascularization and neuronal protection. Methods: The effects of T3 and Nano-T3 + Pcr on angiogenesis were studied in a CAM model. Their cardioprotective effect under hypoxia was studied using isolated neonatal cardiomyocytes treated with PBS (control), T3 (3 uM), Pcr (30 uM) and T3 + Pcr. Mitochondrial function and sarcomere integrity were studied using an ATP- bioluminescence assay, and cardiac Troponin T levels using flow cytometry, respectively. The effect of Nano-T3 on induced neuronal cells under hypoxia was also studied. Finally, Nano-T3-Cy7 were injected into mice tail veins to monitor their biodistribution in real time. Results: Nano-T3 activate the cell surface receptor αvβ3 and is distributed into the cytoplasm, but not the nucleus. Nano-T3 enhanced angiogenesis in the CAM model (~3 fold) versus T3. Under hypoxia, cardiac ATP improvement was achieved with T3+Pcr ( p <0.001) while maintaining normal Troponin T levels. ( Figure 1 ). Nano-T3 produced a significant upregulation of the neural protection markers, PAX6 and DLX2 by ~ 50%. In vivo, the Cy7 signal intensity was detected primarily in mice brains, and hearts, within minutes of administration. Conclusion: Nano-T3 + Pcr represents a potentially new therapeutic for the control of tissue damage in cardiac ischemia and resuscitation.

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