To determine the biochemical and related functional effects of the thyroid 
analog diiodothyroproprionic acid (DITPA) on primate myocardium, we examined, 
both before and after 23 days of DITPA (3.75 mg/kg): myosin heavy-chain (MHC) 
isoforms and sarcoplasmic reticulum (SR) calcium cycling proteins; left 
ventricular (LV) function; and the LV force-frequency relation in four baboons 
chronically instrumented with sonomicrometers and micromanometers. The 
force-frequency relation was measured as the response of isovolumic contraction 
(dP/dtmax) to incremental pacing and the critical heart rate (HRcrit) as the 
rate at which dP/dtmax reached its maximum. DITPA increased basal LV dPt/dtmax 
(3,300 +/- 378 versus 2,943 +/- 413 mm Hg/sec; p = .09), and velocity of 
circumferential shortening (1.13 +/- 0.30 versus 0.76 +/- 0.30 circ/sec; p < 
.01), decreased the basal time constant of isovolumic relaxation (24.2 +/- 1.6 
versus 29.9 +/- 2.5 msec; p < .05), and increased the HRcrit (203 +/- 19 versus 
168 +/- 20 bpm; p < .05), without effecting significant changes in either basal 
heart rate (119 +/- 14 versus 111 +/- 17 bpm) or systolic blood pressure (137 
+/- 14 versus 126 +/- 8 mm Hg). Quantitative immunoblotting revealed significant 
decreases in both phospholamban and the ratio of phospholamban to SR Ca2+ 
adenosine triphosphatase in DITPA-treated animals when compared to four 
untreated controls. By contrast, alpha-MHC isoform was undetectable in both 
DITPA treated and control baboons. Thus, DITPA favorably alters the 
stoichiometry between the SR calcium pump and its inhibitor, phospholamban, and 
has positive inotropic and lusitropic effects in the normal primate left 
ventricle, which may be useful in the treatment of heart failure. Unlike thyroid 
hormone, these changes occur in the absence of detectable alpha-MHC isoform 
protein expression and without an increase in heart rate.