Modification of left ventricular hypertrophy by chronic etomixir treatment

Area of Science:

• Cardiology
• Pharmacology
• Molecular Biology

Background:

• Pressure overload leads to cardiac hypertrophy and functional deterioration.
• Carnitine palmitoyl-transferase 1 (CPT1) inhibition by etomoxir may counteract maladaptive changes in the heart.
• Previous studies suggest etomoxir reduces fetal gene expression and functional decline during pressure overload adaptation.

Purpose of the Study:

• To investigate the effects of etomoxir on depressed myocardial function in hypertrophied ventricles after prolonged pressure overload.
• To test the hypothesis that etomoxir can improve cardiac function in a rat model of sustained pressure overload.

Main Methods:

• Rats underwent ascending aortic constriction to induce pressure overload.
• Racemic etomoxir (15 mg/kg/day) was administered for 6 weeks, starting 6 weeks after aortic constriction.
• Cardiac function, ventricular mass, chamber volume, myocyte isomyosin composition, and pressure-derived parameters were assessed.

Main Results:

• Etomoxir treatment increased the right ventricular/body weight ratio and left ventricular weight.
• Etomoxir blunted left ventricular chamber dilation and shifted isomyosin profiles towards a more efficient phenotype (increased V1, decreased V3).
• Etomoxir significantly enhanced maximal developed pressure, and rates of pressure development and decline, indicating improved myocardial contractility and relaxation.

Conclusions:

• Etomoxir administration improved cardiac function in pressure-overloaded hypertrophied ventricles.
• The drug's coordinated effects on ventricular mass, geometry, and myocyte phenotype enhanced pressure-generating capacity.
• Etomoxir treatment delayed deleterious dilative remodeling in the hypertrophied left ventricle.