Chronic inhibition of fatty acid oxidation: New model of diastolic dysfunction

S. E. Litwin, T. E. Raya, R. G. Gay, J. B. Bedotto, J. J. Bahl, P. G. Anderson, Steven Goldman, R. Bressler

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

This study was designed to determine the changes in the heart that result from inhibition of long-chain fatty acid oxidation with 2-tetradecylglycidic acid (TDGA). Male Sprague-Dawley rats (n = 64) were treated with TDGA (20 mig · kg-1 · day-1) or a comparable volume of vehicle by gavage feeding for 7 or 21 days. In conscious rats TDGA produced no changes in heart rate, left ventricular systolic or end-diastolic pressures, left ventricular pressure development (dP/dt), or the time constant of left ventricular relaxation. Left ventricular developed pressure was not changed at 21 days. TDGA increased left ventricular weight, left ventricular weight-to-body weight ratio, and total heart weight-to-body weight ratio. Left ventricular endocardial and epicardial myocyte volumes were increased by 53 and 65%, respectively. Myocardial triglyceride content was increased threefold. Left ventricular chamber stiffness constants between end-diastolic pressures of 0 and 30 mmHg were increassed, and left ventricular end-diastolic volumes at operating end-diastolic pressures were decreased at both 7 and 21 days. The myocardial stiffness constant was also increased at 7 and 21 days. Thus inhibition of long-chain fatty acid oxidation with TDGA increased left ventricular mass and altered left ventricular chamber and muscle stiffness without changing left ventricular relaxation or systolic function. We conclude that inhibition of long-chain fatty acid oxidation produced an unusual model of left ventricular hypertrophy and diastolic dysfunction characterized by abnormalities of passive-elastic properties but preserved relaxation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume258
Issue number1 27-1
StatePublished - 1990
Externally publishedYes

Fingerprint

Fatty Acids
Ventricular Pressure
Blood Pressure
Weights and Measures
Body Weight
Left Ventricular Hypertrophy
Stroke Volume
Muscle Cells
Sprague Dawley Rats
Triglycerides
Heart Rate
2-tetradecylglycidic acid
Muscles

Keywords

  • 2-tetradecylglycidic acid
  • Cardiac hypertrophy
  • Diastole
  • Fatty acids
  • Metabolism
  • Passive-elastic properties
  • Relaxation
  • Stiffness

ASJC Scopus subject areas

  • Physiology

Cite this

Litwin, S. E., Raya, T. E., Gay, R. G., Bedotto, J. B., Bahl, J. J., Anderson, P. G., ... Bressler, R. (1990). Chronic inhibition of fatty acid oxidation: New model of diastolic dysfunction. American Journal of Physiology - Heart and Circulatory Physiology, 258(1 27-1).

Chronic inhibition of fatty acid oxidation : New model of diastolic dysfunction. / Litwin, S. E.; Raya, T. E.; Gay, R. G.; Bedotto, J. B.; Bahl, J. J.; Anderson, P. G.; Goldman, Steven; Bressler, R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 258, No. 1 27-1, 1990.

Research output: Contribution to journalArticle

Litwin, SE, Raya, TE, Gay, RG, Bedotto, JB, Bahl, JJ, Anderson, PG, Goldman, S & Bressler, R 1990, 'Chronic inhibition of fatty acid oxidation: New model of diastolic dysfunction', American Journal of Physiology - Heart and Circulatory Physiology, vol. 258, no. 1 27-1.
Litwin, S. E. ; Raya, T. E. ; Gay, R. G. ; Bedotto, J. B. ; Bahl, J. J. ; Anderson, P. G. ; Goldman, Steven ; Bressler, R. / Chronic inhibition of fatty acid oxidation : New model of diastolic dysfunction. In: American Journal of Physiology - Heart and Circulatory Physiology. 1990 ; Vol. 258, No. 1 27-1.
@article{5843987123c849d588cedc752def4888,
title = "Chronic inhibition of fatty acid oxidation: New model of diastolic dysfunction",
abstract = "This study was designed to determine the changes in the heart that result from inhibition of long-chain fatty acid oxidation with 2-tetradecylglycidic acid (TDGA). Male Sprague-Dawley rats (n = 64) were treated with TDGA (20 mig · kg-1 · day-1) or a comparable volume of vehicle by gavage feeding for 7 or 21 days. In conscious rats TDGA produced no changes in heart rate, left ventricular systolic or end-diastolic pressures, left ventricular pressure development (dP/dt), or the time constant of left ventricular relaxation. Left ventricular developed pressure was not changed at 21 days. TDGA increased left ventricular weight, left ventricular weight-to-body weight ratio, and total heart weight-to-body weight ratio. Left ventricular endocardial and epicardial myocyte volumes were increased by 53 and 65{\%}, respectively. Myocardial triglyceride content was increased threefold. Left ventricular chamber stiffness constants between end-diastolic pressures of 0 and 30 mmHg were increassed, and left ventricular end-diastolic volumes at operating end-diastolic pressures were decreased at both 7 and 21 days. The myocardial stiffness constant was also increased at 7 and 21 days. Thus inhibition of long-chain fatty acid oxidation with TDGA increased left ventricular mass and altered left ventricular chamber and muscle stiffness without changing left ventricular relaxation or systolic function. We conclude that inhibition of long-chain fatty acid oxidation produced an unusual model of left ventricular hypertrophy and diastolic dysfunction characterized by abnormalities of passive-elastic properties but preserved relaxation.",
keywords = "2-tetradecylglycidic acid, Cardiac hypertrophy, Diastole, Fatty acids, Metabolism, Passive-elastic properties, Relaxation, Stiffness",
author = "Litwin, {S. E.} and Raya, {T. E.} and Gay, {R. G.} and Bedotto, {J. B.} and Bahl, {J. J.} and Anderson, {P. G.} and Steven Goldman and R. Bressler",
year = "1990",
language = "English (US)",
volume = "258",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "1 27-1",

}

TY - JOUR

T1 - Chronic inhibition of fatty acid oxidation

T2 - New model of diastolic dysfunction

AU - Litwin, S. E.

AU - Raya, T. E.

AU - Gay, R. G.

AU - Bedotto, J. B.

AU - Bahl, J. J.

AU - Anderson, P. G.

AU - Goldman, Steven

AU - Bressler, R.

PY - 1990

Y1 - 1990

N2 - This study was designed to determine the changes in the heart that result from inhibition of long-chain fatty acid oxidation with 2-tetradecylglycidic acid (TDGA). Male Sprague-Dawley rats (n = 64) were treated with TDGA (20 mig · kg-1 · day-1) or a comparable volume of vehicle by gavage feeding for 7 or 21 days. In conscious rats TDGA produced no changes in heart rate, left ventricular systolic or end-diastolic pressures, left ventricular pressure development (dP/dt), or the time constant of left ventricular relaxation. Left ventricular developed pressure was not changed at 21 days. TDGA increased left ventricular weight, left ventricular weight-to-body weight ratio, and total heart weight-to-body weight ratio. Left ventricular endocardial and epicardial myocyte volumes were increased by 53 and 65%, respectively. Myocardial triglyceride content was increased threefold. Left ventricular chamber stiffness constants between end-diastolic pressures of 0 and 30 mmHg were increassed, and left ventricular end-diastolic volumes at operating end-diastolic pressures were decreased at both 7 and 21 days. The myocardial stiffness constant was also increased at 7 and 21 days. Thus inhibition of long-chain fatty acid oxidation with TDGA increased left ventricular mass and altered left ventricular chamber and muscle stiffness without changing left ventricular relaxation or systolic function. We conclude that inhibition of long-chain fatty acid oxidation produced an unusual model of left ventricular hypertrophy and diastolic dysfunction characterized by abnormalities of passive-elastic properties but preserved relaxation.

AB - This study was designed to determine the changes in the heart that result from inhibition of long-chain fatty acid oxidation with 2-tetradecylglycidic acid (TDGA). Male Sprague-Dawley rats (n = 64) were treated with TDGA (20 mig · kg-1 · day-1) or a comparable volume of vehicle by gavage feeding for 7 or 21 days. In conscious rats TDGA produced no changes in heart rate, left ventricular systolic or end-diastolic pressures, left ventricular pressure development (dP/dt), or the time constant of left ventricular relaxation. Left ventricular developed pressure was not changed at 21 days. TDGA increased left ventricular weight, left ventricular weight-to-body weight ratio, and total heart weight-to-body weight ratio. Left ventricular endocardial and epicardial myocyte volumes were increased by 53 and 65%, respectively. Myocardial triglyceride content was increased threefold. Left ventricular chamber stiffness constants between end-diastolic pressures of 0 and 30 mmHg were increassed, and left ventricular end-diastolic volumes at operating end-diastolic pressures were decreased at both 7 and 21 days. The myocardial stiffness constant was also increased at 7 and 21 days. Thus inhibition of long-chain fatty acid oxidation with TDGA increased left ventricular mass and altered left ventricular chamber and muscle stiffness without changing left ventricular relaxation or systolic function. We conclude that inhibition of long-chain fatty acid oxidation produced an unusual model of left ventricular hypertrophy and diastolic dysfunction characterized by abnormalities of passive-elastic properties but preserved relaxation.

KW - 2-tetradecylglycidic acid

KW - Cardiac hypertrophy

KW - Diastole

KW - Fatty acids

KW - Metabolism

KW - Passive-elastic properties

KW - Relaxation

KW - Stiffness

UR - http://www.scopus.com/inward/record.url?scp=0025097971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025097971&partnerID=8YFLogxK

M3 - Article

C2 - 2137299

AN - SCOPUS:0025097971

VL - 258

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 1 27-1

ER -