Cardioprotective effect of 3-iodothyronamine in perfused rat heart subjected to ischemia and reperfusion

Sabina Frascarelli, Sandra Ghelardoni, Grazia Chiellini, Elena Galli, Francesca Ronca, Thomas (Tom) Scanlan, Riccardo Zucchi

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Abstract

3-iodothyronamine (T 1AM) is an endogenous compound which shares structural and functional features with biogenic amines and is able to interact with a specific class of receptors, designed as trace amine associated receptors. T 1AM has significant physiological effects in mammals and produces a reversible, dose-dependent negative inotropic and chronotropic effect in heart. The aim of the present study was to investigate if T 1AM is able to reduce irreversible tissue injury in isolated rat hearts subjected to ischemia and reperfusion, as evaluated by triphenyltetrazolium chloride staining. We observed that T 1AM reduced infarct size at concentrations (125 nM to 12.5 μM) which did not produce any significant hemodynamic action. The dose-response curve was bell-shaped and peaked at 1.25 μM. T 1AM-induced cardioprotection was completely reversed by the administration of chelerythrine and glibenclamide, suggesting a protein kinase C and K ATP + -dependent pathway, while it was not additive to the protection induced by cyclosporine A, suggesting modulation of mitochondrial permeability transition. At cardioprotective concentration, T 1AM reduced the time needed for cardiac attest during ischemia, but it did not affect sarcoplasmatic reticulum Ca 2+ handling, as demonstrated by unaltered ryanodine receptor binding properties. In conclusion, in isolated rat heart T 1AM produces a cardioprotective effect which is mediated by a protein kinase C and K ATP + -dependent pathway and is probably linked to modulation of mitochondrial permeability transition and/or ischemic arrest time.

Original languageEnglish (US)
Pages (from-to)307-313
Number of pages7
JournalCardiovascular Drugs and Therapy
Volume25
Issue number4
DOIs
Publication statusPublished - Aug 2011

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Keywords

  • 3-iodothyronamine
  • Heart
  • Ischemia
  • Reperfusion
  • Thyroid hormone

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Cardioprotective effect of 3-iodothyronamine in perfused rat heart subjected to ischemia and reperfusion. / Frascarelli, Sabina; Ghelardoni, Sandra; Chiellini, Grazia; Galli, Elena; Ronca, Francesca; Scanlan, Thomas (Tom); Zucchi, Riccardo.

In: Cardiovascular Drugs and Therapy, Vol. 25, No. 4, 08.2011, p. 307-313.

Research output: Contribution to journalArticle