Development of a thyroid hormone analogue for the treatment of congestive heart failure

Eugene Morkin, Gregory D. Pennock, Thomas E. Raya, Joseph J. Bahl, Steven Goldman

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The possibility that thyroid hormone or a thyroid hormone analogue that improves cardiac performance might be useful in the treatment of heart failure has been examined. In the rat postinfarction model of heart failure, treatment with low doses (1.5 μg/100 g) of thyroxine (T4) for 3 days produced a positive inotropic response, including an increase in left ventricular (LV) dP/dt and a decrease in LV end-diastolic pressure (LVEDP). When treatment with T4 was continued at the same or higher doses (3 to 15 μg/100 g) for 10-12 days, heart rate was increased and improvement in LVEDP was not sustained. To identify an analogue with a more favorable hemodynamic profile, single- and double-ring compounds related to T4 were screened for thyromimetic activity in heart cell cultures and for their ability to bind thyroid hormone receptors. One of the analogues selected, 3,5- diiodothyropropionic acid (DITPA), was found to have inotropic selectivity in hypothyroid rats. When administered (375 μg/100 g) to rats with ventricular dysfunction after myocardial infarction in combination with captopril, there was improvement of the resting and stressed cardiac index and LV filling pressure. Similar improvement in cardiac performance was obtained when DITPA was administered to rabbits after infarction. Thus a thyroid hormone analogue with inotropic selectivity may be a useful adjunct to other measures in the treatment of heart failure.

Original languageEnglish (US)
Pages (from-to)521-526
Number of pages6
JournalThyroid
Volume6
Issue number5
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Development of a thyroid hormone analogue for the treatment of congestive heart failure'. Together they form a unique fingerprint.

Cite this