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Serial Course of Left Ventricular Function, Perfusion and Fatty Acid Uptake in the Cardiomyopathic Hamster

Division of Nuclear Medicine, Massachusetts General Hospital, and Department of Radiology, Harvard Medical School, Boston, Massachusetts

Correspondence: For correspondence or reprints contact: H. William Strauss, MD, Bristol-Myers Squibb Co., P.O. Box 4000, Princeton, NJ 08543-4000.

ABSTRACT

To determine the relationship of metabolic and perfusion changes to alterations in ventricular function in the course of cardiomyopathy, we performed serial measurements of ejection fraction, myocardial perfusion, fatty acid uptake of 3-methyl-p[¹²³I]-phenyl-pentadecanoic acid ([¹²³I]3MPDA) and myocardial histology in Syrian hamsters genetically predisposed to the development of congestive cardiomyopathy (Bio T0-2) (n = 30) and normal age-matched control animals (Bio F1B) (n = 13). To obtain high-resolution information about the myocardium at the time of onset of the first noticeable decrease in ventricular function, a multitracer autoradiographic study using ^99mTc-pyrophosphate, ²⁰¹Tl and [¹⁴C]3MPDA was obtained at 90 days of age. Baseline ejection fraction recorded at 60 days averaged 60.3%; by 90 days, it decreased to 54.3% (p < 0.05), falling to 41.3% at 180 days (p < 0.01) and declining to 30% at the end of the study. A progressive increase in the extent of myocytolysis, fibrosis and calcification was seen in the histologic studies as the animals aged. The ratio of fatty acid-to-thallium uptake dropped from 0.51 ± 0.09 to 0.45 ± 0.11 (p < 0.01), which is in parallel with the reduction in ejection fraction. The thallium lung-to-heart ratio increased from 0.51 at 90 days to 0.59 at 270 days (p < 0.05), which corresponds to the worsening of cardiac function. The macroautoradiographic studies demonstrated slight uptake of pyrophosphate in the myopathic hamster hearts and minimal changes in the regional distribution of fatty acid compared to that of perfusion. We conclude that the decrease in ventricular function parallels the severity of myocytolysis and fibrosis. Although decreased fatty acid uptake was apparent at an early stage, the extent of the change is modest and is difficult to detect from external images.

FOOTNOTES

^* Present address: Clinical Pathology & Second Internal Medicine, Iwate Medical University, Morioka, Japan 020.

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