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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1992-11-20
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pubmed:abstractText |
Thyroid hormone exerts a strong positive inotropic action on the heart and induces alpha-myosin heavy chain (MHC) gene expression. 3,5-Diiodothyropropionic acid (DITPA), a carboxylic acid analog with low metabolic activity, was observed to induce alpha-MHC mRNA in heart cell culture with EC50 approximately 5 x 10(-7) M. To determine if the compound has positive inotropic actions, the effects of DITPA and L-thyroxine on heart rate, left ventricular pressures, left ventricular dP/dt, myosin isoenzymes and hepatic alpha-glycerolphosphate dehydrogenase activity were compared in hypothyroid rats. Binding affinities of DITPA and triiodothyronine for bacterially expressed alpha-1 and beta-1 thyroid hormone receptors (TRs) also were determined. Over the dosage range of 150 to 1500 micrograms/100 g, DITPA produced increases in left ventricular dP/dt comparable to those obtained with L-thyroxine at dosages of 1.5 to 15 micrograms/100 g, but with significantly less tachycardia. The increase in alpha-MHC mRNA was about the same with both compounds whereas alpha-MHC protein content and GPDH activity increased less with DITPA. These differences could not be explained by preferential binding of DITPA to TR subtypes. Because heart rate is a major determinant of myocardial oxygen consumption, DITPA is able to achieve increased cardiac performance at lower myocardial oxygen costs.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
263
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
163-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:1403782-Animals,
pubmed-meshheading:1403782-Body Weight,
pubmed-meshheading:1403782-Cardiotonic Agents,
pubmed-meshheading:1403782-Cells, Cultured,
pubmed-meshheading:1403782-Diiodothyronines,
pubmed-meshheading:1403782-Heart,
pubmed-meshheading:1403782-Heart Rate,
pubmed-meshheading:1403782-Male,
pubmed-meshheading:1403782-Myocardial Contraction,
pubmed-meshheading:1403782-Myosins,
pubmed-meshheading:1403782-Organ Size,
pubmed-meshheading:1403782-Rats,
pubmed-meshheading:1403782-Rats, Sprague-Dawley,
pubmed-meshheading:1403782-Thyroxine
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pubmed:year |
1992
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pubmed:articleTitle |
Cardiac effects of 3,5-diiodothyropropionic acid, a thyroid hormone analog with inotropic selectivity.
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pubmed:affiliation |
Department of Cardiology, Tucson Veterans Administration Medical Center, Arizona.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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