Linked Life Data

21131480

Source:http://linkedlifedata.com/resource/pubmed/id/21131480

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-2-1
pubmed:abstractText
There is emerging evidence that treatment with thyroid hormone (TH) can improve postischemic cardiac function. 3,5-Diiodothyropropionic acid (DITPA), a TH analog, has been proposed to be a safer therapeutic agent than TH because of its negligible effects on cardiac metabolism and heart rate. However, conflicting results have been reported for the cardiac effects of DITPA. Importantly, recent clinical trials demonstrated no symptomatic benefit in patients with DITPA despite some improved hemodynamic and metabolic parameters. To address these issues, dose-dependent effects of DITPA were investigated in mice for baseline cardiovascular effects and postischemic myocardial function and/or salvage. Mice were treated with subcutaneous DITPA at 0.937, 1.875, 3.75, or 7.5 mg·kg(-1)·day(-1) for 7 days, and the results were compared with untreated mice for ex vivo and/or in vivo myocardial ischemia-reperfusion (I/R). DITPA had no effects on baseline body temperature, body weight, or heart rate; however, it mildly increased blood pressure. In isolated hearts, baseline contractile function was significantly impaired in DITPA-pretreated mice; however, postischemic recovery was comparable between untreated and DITPA-treated groups. In vivo baseline cardiac parameters were significantly affected by DITPA, with increased ventricular dimensions and decreased contractile function. Importantly, DITPA-treated mice demonstrated high prevalence of fatal cardiac rhythm abnormalities during in vivo ischemia and/or reperfusion. There were no improvements in myocardial infarction and postischemic fractional shortening with DITPA. Myocardial sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), phospholamban (PLB), and heat shock protein (HSP) levels remained unchanged with DITPA treatment. Thus DITPA administration impairs baseline cardiac parameters in mice and can be fatal during in vivo acute myocardial I/R.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H702-11
pubmed:dateRevised
2011-8-8
pubmed:meshHeading
pubmed-meshheading:21131480-Animals, pubmed-meshheading:21131480-Arrhythmias, Cardiac, pubmed-meshheading:21131480-Blood Pressure, pubmed-meshheading:21131480-Blotting, Western, pubmed-meshheading:21131480-Cardiotonic Agents, pubmed-meshheading:21131480-Data Interpretation, Statistical, pubmed-meshheading:21131480-Diiodothyronines, pubmed-meshheading:21131480-Dose-Response Relationship, Drug, pubmed-meshheading:21131480-Echocardiography, pubmed-meshheading:21131480-Electrocardiography, pubmed-meshheading:21131480-Heart, pubmed-meshheading:21131480-Male, pubmed-meshheading:21131480-Mice, pubmed-meshheading:21131480-Mice, Inbred C57BL, pubmed-meshheading:21131480-Myocardial Infarction, pubmed-meshheading:21131480-Myocardial Reperfusion Injury, pubmed-meshheading:21131480-Propionic Acids, pubmed-meshheading:21131480-Sympathomimetics, pubmed-meshheading:21131480-Thyroxine, pubmed-meshheading:21131480-Triiodothyronine, pubmed-meshheading:21131480-Ventricular Function, Left
pubmed:year
2011
pubmed:articleTitle
Detrimental effects of thyroid hormone analog DITPA in the mouse heart: increased mortality with in vivo acute myocardial ischemia-reperfusion.
pubmed:affiliation
Davis Heart and Lung Research Institute, Department of Internal Medicine, Ohio State University College of Medicine, 473 West 12th Ave., Columbus, OH 43210, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, N.I.H., Extramural