title: Alterations in myocardial free fatty acid clearance precede mechanical abnormalities in canine tachycardia-induced heart failure.
abstract: BACKGROUND
  The purpose of this study was to evaluate whether abnormalities of free fatty acid metabolism are present before the onset of overt mechanical dysfunction in dogs with tachycardia-induced heart failure. We studied six dogs chronically instrumented to allow assessment of left ventricular function in the pressure-volume plane.
  
  
  RESULTS
  Free fatty acid clearance was assessed according to the washout rate of a free fatty acid analog, iodophenylpentadecanoic acid ([123I]PPA or IPPA). IPPA clearance was measured within 1 hour of the hemodynamic assessment. The animals were studied under baseline conditions and 11.7 +/- 3.6 days after ventricular pacing at a rate of 240 beats/min. Hemodynamic studies after pacing showed a nonsignificant increase in left ventricular end-diastolic pressure (11.7 +/- 4.7 to 17.4 +/- 6.5 mm Hg) and a nonsignificant decrease in the maximum derivative of pressure with respect to time (1836 +/- 164 vs 1688 +/- 422 mm Hg/sec). There was also no change in the time constant of left ventricular relaxation, which was 34.8 +/- 7.67 msec before and 35.3 +/- 7.3 msec after pacing. However, a significant prolongation in the clearance half-time of [123I]PPA, from 86.1 +/- 23.9 to 146.5 +/- 22.6 minutes (p < 0.01) was found. Thus abnormal lipid clearance appears before the onset of significant mechanical dysfunction in tachycardia-induced heart failure.
  
  
  CONCLUSIONS
  This suggests that abnormal substrate metabolism may play an important role in the pathogenesis of this condition.
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Freeman
authors.forename: J T
authors.initials: JT
authors.lastname: Colston
authors.forename: D D
authors.initials: DD
authors.lastname: Miller
mesh_terms: D000818:Animals; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D013610:Tachycardia / Q000503:physiopathology; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*
chemical_list: D005230:Fatty Acids, Nonesterified; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; C025391:omega-(4-iodophenyl)pentadecanoic acid