DITPA prevents the blunted contraction-frequency relationship in myocytes from infarcted hearts

Loss of the positive force-frequency relationship is a characteristic findi ng in failing hearts. The mechanisms of this change are not well understood . Myocardial infarction (MI) was induced in rabbits to produce left ventric ular (LV) dysfunction. Beginning 1 day after MI, a subgroup of rabbits rece ived diiodothyropropionic acid (DITPA) (3.75 mg.kg(-1).day(-1) sc) for 3 wk . We measured contractions, Ca2+ transients, action potentials, and sarcopl asmic reticulum (SR) Ca2+ content at different stimulation rates in single LV myocytes. The shortening-frequency relationship was markedly flattened i n MI myocytes compared with control myocytes. In addition, Ca2+ transients, action potentials, and contractions were prolonged. Myocytes from DITPA-tr eated MI rabbits had preserved inotropic responses to increased stimulation rate and normal duration of action potentials and Ca2+ transients. SR Ca2 content increased significantly when stimulation rate was increased from 0 .5 to 2.0 Hz in control myocytes but did not change significantly in MI myo cytes. Myocytes from DITPA-treated MI rabbits had a greater frequency-depen dent increase in SR Ca2+ content compared with the untreated MI rabbits. Th us single myocytes from infarcted rabbit hearts have frequency-dependent ab normalities of contractility, Ca2+ cycling, and action potential repolariza tion. The flattened contraction-frequency relationship can be partially exp lained by an attenuation of the normal enhancement of SR Ca2+ content that occurs when stimulation rate is increased. Chronic DITPA administration aft er MI largely prevents the development of these abnormalities.