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.
Methods and 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.
This suggests that abnormal substrate metabolism may play an important role in the pathogenesis of this condition.
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Freeman, G.L., Colston, J.T. & Miller, D.D. Alterations in myocardial free fatty acid clearance precede mechanical abnormalities in canine tachycardia-induced heart failure. J Nucl Cardiol 1, 171–179 (1994). https://doi.org/10.1007/BF02984089
- cardiac metabolism