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.