3,5-Diiodothyronine protects against cardiac ischaemia–reperfusion injury in male rats

Ruy Andrade Louzada, Alvaro Souto Padron, Silvio Rodrigues Marques-Neto, Leonardo Maciel, João Pedro Werneck-de-Castro, Andrea Claudia Freitas Ferreira, Jose Hamilton Matheus Nascimento, Denise Pires Carvalho

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


New Findings: What is the central question of this study? 3,5-Diiodothyronine (3,5-T2) administration increases resting metabolic rate, prevents or treats liver steatosis in rodent models, and ameliorates insulin resistance: what are its effects on cardiac electrical and contractile properties and autonomic regulation? 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 ischaemia–reperfusion injury. Abstract: The use of 3,5,3′-triiodothyronine (T3) and thyroxine (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 made so far. Three-month-old Wistar rats were daily administered vehicle, 3,5-T2 or 3,5-T2+T4 and no signs of atrial or ventricular arrhythmia were detected in non-anaesthetized rats during 90 days. Cardiac function was preserved as heart rate, left ventricle diameter and shortening fraction in 3,5-T2-treated rats compared to vehicle and 3,5-T2+T4 groups. Power spectral analysis indicated an amelioration of the heart rate variability only in 3,5-T2-treated rats. An increased baroreflex sensitivity at rest was 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 ischaemia–reperfusion injury. In conclusion, chronic 3,5-T2 administration ameliorates tonic cardiac autonomic control and confers cardioprotection against ischaemia–reperfusion injury in healthy male rats.

Original languageEnglish (US)
Pages (from-to)2185-2197
Number of pages13
JournalExperimental Physiology
Issue number11
StatePublished - Nov 1 2021


  • 3,5-T2
  • autonomous control
  • echocardiography
  • electrocardiography
  • infarct size
  • ischaemia–reperfusion injury

ASJC Scopus subject areas

  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)


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