Heart failure of diverse causes is associated with abnormalities of sarcoplasmic 
reticulum (SR) Ca(2+)transport. The purpose of this study was to determine 
whether the thyroid hormone analogue, 3,5-diiodothyropropionic acid (DITPA), 
prevents abnormal Ca(2+)transport and expression of SR proteins associated with 
post-infarction heart failure. New Zealand White rabbits were randomly assigned 
to circumflex artery ligation or sham operation, and to DITPA administration 
(3.75 mg/kg/day) or no treatment in a two-by-two factorial design. After 3 
weeks, echo-Doppler and LV hemodynamic measurements were performed. From 
ventricular tissue, single myocyte shortening and relaxation were determined, 
and Ca(2+)transport was measured in homogenates and SR-enriched microsomes. 
Levels of mRNA and protein content were determined for the SR Ca(2+)-ATPase 
(SERCA2a), phospholamban (PLB), cardiac ryanodine receptor (RyR-2) and 
calsequestrin. The administration of DITPA improved LV contraction and 
relaxation and improved myocyte shortening in infarcted animals. The 
improvements in LV and myocyte function were associated with increases in 
V(max)for SR Ca(2+)transport in both homogenates and microsomes. Also, DITPA 
prevented the decrease in LV protein density for SERCA2a, PLB and RyR-2 
post-infarction, without measurable changes in mRNA levels. The thyroid hormone 
analogue, DITPA, improves LV, myocyte and SR function in infarcted hearts and 
prevents the downregulation of SR proteins associated with post-infarction heart 
failure. The specific effects of DITPA on post-infarction SR Ca(2+)transport and 
the expression of SR proteins make this compound a potentially useful 
therapeutic agent for LV systolic and/or diastolic dysfunction.