3,5-diiodothyronine (3,5-T2) protects against cardiac ischemia-reperfusion injury in male rats.

NEW FINDINGS What is the central question of this study? It is recognized that 3,5-diiodothyronine (3,5-T2) administration increases resting metabolic rate, prevents or treats liver steatosis in rodent models and ameliorates insulin resistance, suggesting 3,5-T2 as a potential therapeutic tool. However, a comprehensive assessment of cardiac electrical and contractile properties, and autonomic regulation has not been assessed so far. What is the main finding and its importance? Chronic 3,5-T2 administration has no adverse effects on cardiac function. Remarkably, 3,5-T2 improves the autonomous control of the rat heart and protects against ischemia-reperfusion injury. ABSTRACT The use of T3 and T4 to treat metabolic diseases has been hindered by potential adverse effects on liver, lipid metabolism and cardiac electrical properties. It is recognized that 3,5-diiodothyronine (3,5-T2) administration increases resting metabolic rate, prevents or treats liver steatosis in rodent models and ameliorates insulin resistance, suggesting 3,5-T2 as a potential therapeutic tool. However, a comprehensive assessment of cardiac electrical and contractile properties has not been assessed so far. Three-month-old Wistar rats were daily administrated with vehicle, 3,5-T2 and 3,5-T2 + thyroxine (T4) and no signs of atrial or ventricular arrhythmia were detected in non-anesthetized rats for 90 days. Cardiac function was preserved as heart rate, left ventricle diameters and shortening fraction in 3,5-T2-treated rats compared to vehicle and 3,5-T2+T4 groups. Power spectral analysis of heart rate variability (HRV) indicated an amelioration of the heart rate variability only in 3,5-T2-treated rats. An increased baroreflex sensitivity at rest were observed in both 3,5-T2 treated groups. Finally, 3,5-T2 Langendorff-perfused hearts presented a significant recovery of left ventricular function and remarkably smaller infarction area after ischemia-reperfusion injury. In conclusion, chronic 3,5-T2 administration ameliorates tonic cardiac autonomic control and confers cardioprotection against ischemia/reperfusion injury in healthy male rats. This article is protected by copyright. All rights reserved.