title: Etomoxir improves left ventricular performance of pressure-overloaded rat heart.
abstract: BACKGROUND
  Numerous studies have demonstrated diverse abnormalities in subcellular structures of pressure-overloaded hypertrophied and failing heart. Long-term administration of etomoxir, a carnitine palmitoyltransferase-1 inhibitor, partially normalized the proportion of myosin isozyme V1 and number of active Ca2+ pumps in hypertrophied rat myocardium.
  
  
  RESULTS
  To test the hypothesis that long-term etomoxir treatment improves the performance of hypertrophied ventricle, sham-operated rats and rats with ascending aorta constriction were treated with racemic etomoxir (15 mg/kg per day) for 12 weeks. Left ventricular geometry, dynamics of isovolumic contractions, as well as myosin isozymes as marker of etomoxir-induced phenotype changes were assessed. Etomoxir stimulated (P<.05) slight hypertrophic growth in right and left ventricles of sham-operated rats as well as in right ventricles but not in overloaded left ventricles of rats with aortic constriction. In all treated rats, etomoxir increased (P<.05) maximal developed pressure, left ventricular pressure-volume area, and +/- dP/dt(max). Enhanced values (P<.05) of derived indexes of myocardial performance (normalized stress-length area, maximal rate of wall stress rise, and decline) indicated that myocardial changes were responsible for the improved performance. The etomoxir treatment increased selectively (P<.05) the proportion of myosin V1 in pressure-overloaded left ventricles.
  
  
  CONCLUSIONS
  The long-term treatment with etomoxir improved functional capacity of pressure-overloaded left ventricle, which can be attributed to an enhanced myocardial performance. Chronic carnitine palmitoyltransferase-1 inhibition may thus represent a candidate approach for developing novel agents that are useful in the prevention of undesirable consequences of pressure overload-induced cardiac hypertrophy.
authors.affiliation: Institute of Pathophysiology, Medical School, Comenius University, Bratislava, Slovak Republic. turcani@medik.fmed.uniba.sk
authors.forename: M
authors.initials: M
authors.lastname: Turcani
authors.forename: H
authors.initials: H
authors.lastname: Rupp
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001810:Blood Volume / Q000502:physiology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000201:enzymology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D007527:Isoenzymes; D002334:Carnitine O-Palmitoyltransferase; D018995:Myosin Heavy Chains; D009218:Myosins; C054207:etomoxir