Severely hypertensive Dahl strain rats, in the early stages of congestive heart failure, demonstrated focal zones of reduced fatty acid uptake in their left ventricular endocardium and free wall. The decrease in fatty acid uptake was accompanied by a complimentary increase in glucose uptake, although perfusion remained uniform. These observations suggest that in the chronically pressure overloaded, hypertrophied, ventricle, metabolic and functional changes occur in temporal proximity. The observation that 'dysfunctional' myocardium has decreased fatty acid uptake while perfusion is uniform suggests that measurement of regional fatty acid uptake will be useful as an indicator of the contractile integrity of the myocardium. To test this hypothesis we propose to perform serial measurements of fatty acid uptake, perfusion, ventricular function and myocardial ultrastructure in Dahl strain rats with evolving myocardial hypertrophy due to severe hypertension. When the relationship of changes in fatty acid uptake, function and morphometry are defined, two drug intervention studies will be performed in additional groups of rats. The first study will test the ability of early therapy with calcium channel blockers and beta blockade to prevent the decrease of fatty acid uptake and function. The second study will determine if therapy with digoxin, calcium channel blockade, or beta blockade started after rest left ventricular ejection fraction has decreased can prevent further deterioration of fatty acid uptake and function. In parallel with the animal studies, patients with left ventricular hypertrophy will be evaluated by planar and SPECT imaging of the distribution of fatty acid, left ventricular function and perfusion.
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| Fischman, A J; Rubin, R H; Khaw, B A et al. (1989) Radionuclide imaging of experimental atherosclerosis with nonspecific polyclonal immunoglobulin G. J Nucl Med 30:1095-100 |
