Tissue distribution and cardiac metabolism of 3-iodothyronamine.
ABSTRACT 3-iodothyronamine (T1AM) is a novel relative of thyroid hormone, able to interact with specific G protein-coupled receptors, known as trace amine-associated receptors. Significant functional effects are produced by exogenous T1AM, including a negative inotropic and chronotropic effect in cardiac preparations. This work was aimed at estimating endogenous T1AM concentration in different tissues and determining its cardiac metabolism. A novel HPLC tandem mass spectrometry assay was developed, allowing detection of T1AM, thyronamine, 3-iodothyroacetic acid, and thyroacetic acid. T1AM was detected in rat serum, at the concentration of 0.3±0.03 pmol/ml, and in all tested organs (heart, liver, kidney, skeletal muscle, stomach, lung, and brain), at concentrations significantly higher than the serum concentration, ranging from 5.6±1.5 pmol/g in lung to 92.9±28.5 pmol/g in liver. T1AM was also identified for the first time in human blood. In H9c2 cardiomyocytes and isolated perfused rat hearts, significant Na+-dependent uptake of exogenous T1AM was observed, and at the steady state total cellular or tissue T1AM concentration exceeded extracellular concentration by more than 20-fold. In both preparations T1AM underwent oxidative deamination to 3-iodothyroacetic acid. T1AM deamination was inhibited by iproniazid but not pargyline or semicarbazide, suggesting the involvement of both monoamine oxidase and semicarbazide-sensitive amine oxidase. Thyronamine and thyroacetic acid were not detected in heart. Finally, evidence of T1AM production was observed in cardiomyocytes exposed to exogenous thyroid hormone, although the activity of this pathway was very low.
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Article: Saphenous vein graft intervention.[show abstract] [hide abstract]
ABSTRACT: Saphenous vein grafts are commonly used conduits for surgical revascularization of coronary arteries but are associated with poor long-term patency rates. Percutaneous revascularization of saphenous vein grafts is associated with worse clinical outcomes including higher rates of in-stent restenosis, target vessel revascularization, myocardial infarction, and death compared with percutaneous coronary intervention of native coronary arteries. Use of embolic protection devices is a Class I indication according to the American College of Cardiology/American Heart Association guidelines to decrease the risk of distal embolization, no-reflow, and periprocedural myocardial infarction. Nonetheless, these devices are underused in clinical practice. Various pharmacological agents are available that may also reduce the risk of or mitigate the consequences of no-reflow. Covered stents do not decrease the rates of periprocedural myocardial infarction and restenosis. Most available evidence supports treatment with drug-eluting stents in this high-risk lesion subset to reduce angiographic and clinical restenosis, although large, randomized trials comparing drug-eluting stents and bare-metal stents are needed.08/2011; 4(8):831-43. · 1.07 Impact Factor
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ABSTRACT: 3-Iodothyronamine (T(1)AM) is a novel relative of thyroid hormone that plays a role in critical body regulatory processes such as glucose metabolism, thermal regulation, and heart beating. This paper was aimed at characterizing time dynamics of T(1)AM and its catabolite 3-iodothyroacetic acid (TA(1)) in different biological scales with linear time-invariant models. Culture medium samples coming from culture of H9c2 murine cells and perfusion liquid samples from perfused rat heart were collected after the injection of a T(1)AM bolus. T(1)AM and TA(1) concentrations in the samples were assayed with high-performance liquid chromatography coupled to tandem mass spectrometry. Kinetic constants relative to T(1)AM transport and conversion were estimated with weighted least-squares method. We found that these constants can be related with an allometric power law depending on mass, with a negative exponent of -0.27 ± 0.19, implying that the velocity of conversion and internalization of T(1)AM decreases with increasing of system mass.IEEE transactions on bio-medical engineering 08/2011; 58(12):3513-7. · 2.15 Impact Factor
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ABSTRACT: 3-iodothyronamine (T(1)AM) 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(1)AM 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(1)AM 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(1)AM 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(1)AM-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(1)AM 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(1)AM 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.Cardiovascular Drugs and Therapy 08/2011; 25(4):307-13. · 2.67 Impact Factor