Cardioprotective Effect of 3-Iodothyronamine in Perfused Rat Heart Subjected to Ischemia and Reperfusion

3-iodothyronamine (T₁AM) 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. T₁AM 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 T₁AM 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 T₁AM 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. T₁AM-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, T₁AM reduced the time needed for cardiac attest during ischemia, but it did not affect sarcoplasmatic reticulum Ca²⁺ handling, as demonstrated by unaltered ryanodine receptor binding properties. In conclusion, in isolated rat heart T₁AM 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.