Induction of myocardial hypertrophy after coronary ligation in rats decreases ventricular dilatation and improves systolic function.

Abstract

BACKGROUND:

Previous studies have shown that hypertrophy of surviving myocytes after myocardial infarction (MI) is limited. Progressive ventricular dilatation after MI may occur when compensatory hypertrophy cannot restore left ventricular (LV) wall stress to normal.

METHODS AND RESULTS:

To test whether induction of additional myocyte hypertrophy might prevent pathological LV remodeling after large MI, we administered 2-tetradecylglycidic acid (TDGA) 20 mg/kg/day to sham-operated (n = 12) and MI (n = 10) rats for 10 days, beginning the third day after infarction. We have previously shown that chronic inhibition of long-chain fatty acid oxidation with TDGA in rats results in myocardial hypertrophy without any apparent impairment of LV systolic function. When compared with untreated MI rats (n = 9), we found that TDGA-treated MI rats had increases in LV weight/body wt, myocyte cross-sectional area, and peak developed LV pressure during abrupt aortic occlusion. MI rats treated with TDGA had lower LV end-diastolic pressures and smaller end-diastolic volumes, whereas stroke volume was maintained. The ex vivo passive LV pressure-volume relation was shifted toward the pressure axis compared with untreated infarct rats. In sham-operated rats, TDGA caused increases in LV weight/body wt, myocyte size, peak developed LV pressure, cardiac index, and stroke volume index, and a shift of the passive LV pressure-volume relation toward the pressure axis.

CONCLUSIONS:

Induction of myocardial hypertrophy with an inhibitor of long-chain fatty acid oxidation retarded the process of LV dilatation and produced beneficial effects on systolic function after large myocardial infarction. These data support the hypothesis that inadequate hypertrophy of residual myocardium after infarction may contribute to LV dilatation and the development of congestive heart failure.

• Authors: S E Litwin, T E Raya, P G Anderson, C M Litwin, R Bressler, S Goldman
• Journal: Circulation (Circulation) Vol. 84 Issue 4 Pg. 1819-27 (Oct 1991) ISSN: 0009-7322 [Print] United States
• PMID: 1833090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epoxy Compounds
• Fatty Acids
• 2-tetradecylglycidic acid

Topics

• Animals
• Cardiomegaly (chemically induced, physiopathology)
• Coronary Vessels (surgery)
• Epoxy Compounds (therapeutic use)
• Fatty Acids (therapeutic use)
• Hemodynamics (drug effects)
• Male
• Microscopy, Electron
• Myocardial Infarction (drug therapy, pathology, physiopathology)
• Myocardium (ultrastructure)
• Rats
• Rats, Inbred Strains
• Ventricular Function, Left (physiology)