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

16 Citations (Scopus)

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
StatePublished - 1996

Fingerprint

Thyroid Hormones
Heart Failure
Treatment Failure
Blood Pressure
Ventricular Dysfunction
Thyroid Hormone Receptors
Captopril
Ventricular Pressure
Thyroxine
Infarction
Cell Culture Techniques
Heart Rate
Hemodynamics
Myocardial Infarction
Rabbits
Acids

ASJC Scopus subject areas

  • Endocrinology

Cite this

Morkin, E., Pennock, G. D., Raya, T. E., Bahl, J. J., & Goldman, S. (1996). Development of a thyroid hormone analogue for the treatment of congestive heart failure. Thyroid, 6(5), 521-526.

Development of a thyroid hormone analogue for the treatment of congestive heart failure. / Morkin, Eugene; Pennock, Gregory D.; Raya, Thomas E.; Bahl, Joseph J.; Goldman, Steven.

In: Thyroid, Vol. 6, No. 5, 1996, p. 521-526.

Research output: Contribution to journalArticle

Morkin, E, Pennock, GD, Raya, TE, Bahl, JJ & Goldman, S 1996, 'Development of a thyroid hormone analogue for the treatment of congestive heart failure', Thyroid, vol. 6, no. 5, pp. 521-526.
Morkin, Eugene ; Pennock, Gregory D. ; Raya, Thomas E. ; Bahl, Joseph J. ; Goldman, Steven. / Development of a thyroid hormone analogue for the treatment of congestive heart failure. In: Thyroid. 1996 ; Vol. 6, No. 5. pp. 521-526.
@article{2c6f79bb11ff42a0880583353ae732bc,
title = "Development of a thyroid hormone analogue for the treatment of congestive heart failure",
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.",
author = "Eugene Morkin and Pennock, {Gregory D.} and Raya, {Thomas E.} and Bahl, {Joseph J.} and Steven Goldman",
year = "1996",
language = "English (US)",
volume = "6",
pages = "521--526",
journal = "Thyroid",
issn = "1050-7256",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - Development of a thyroid hormone analogue for the treatment of congestive heart failure

AU - Morkin, Eugene

AU - Pennock, Gregory D.

AU - Raya, Thomas E.

AU - Bahl, Joseph J.

AU - Goldman, Steven

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0029999556&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029999556&partnerID=8YFLogxK

M3 - Article

C2 - 8936682

AN - SCOPUS:0029999556

VL - 6

SP - 521

EP - 526

JO - Thyroid

JF - Thyroid

SN - 1050-7256

IS - 5

ER -