Assessment of Myocardial Metabolism in Diabetic Rats Using Small-Animal PET: A Feasibility Study

摘要

id="p-1">This feasibility study was undertaken to determine whether kinetic modeling in conjunction with small-animal PET could noninvasively quantify alterations in myocardial perfusion and substrate metabolism in rats. >Methods: All small-animal PET was performed on either of 2 tomographs. Myocardial blood flow and substrate metabolism were measured in 10 male Zucker diabetic fatty rats (ZDF, fa/fa) and 10 lean littermates (Lean, Fa/+) using 15O-water, 1-11C-glucose, 1-11C-acetate, and 1-11C-palmitate. Animals were 12.0 ?± 1.4-wk old. >Results: Consistent with a type 2 diabetic phenotype, the ZDF animals showed higher plasma hemoglobin A_1c, insulin, glucose, and free fatty acid (FFA) levels than their lean controls. Myocardial glucose uptake (mL/g/min) was not significantly different between the 2 groups. However, higher glucose plasma levels in the ZDF rats resulted in higher myocardial glucose utilization (nmol/g/min) (Lean, 629 ?± 785, vs. ZDF, 1,737 ?± 1,406; P = 0.06). Similarly, myocardial FFA uptake (mL/g/min) was not significantly different between the 2 groups, (Lean, 0.51 ?± 28, vs. ZDF, 0.72 ?± 0.19; P = not significant) However, due to higher FFA plasma levels, utilization and oxidation (nmol/g/min) were significantly higher in the ZDF group (Lean, 519 ?± 462, vs. ZDF, 1,623 ?± 712, P .001; and Lean, 453 ?± 478, vs. ZDF, 1,636 ?± 730, P .01). >Conclusion: Noninvasive measurements of myocardial substrate metabolism in ZDF rats using small-animal PET are consistent with the expected early metabolic abnormalities that occur in this well-characterized model of type 2 diabetes mellitus. Thus, small-animal PET demonstrates significant promise in providing a means to link the myocardial metabolic abnormalities that occur in rat of disease with the human condition.