A study of changes in glucose and fatty acid metabolism in the heart as a function of hypertrophy in SHR models using microPET and microSPECT technology

Abstract

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Objectives: Altered myocardial energy metabolism is believed to be one mechanism that contributes to the progression of heart failure. Imaging studies have shown that during heart failure, changes occur in the preferential substrate for myocardial metabolism. Therefore, shifts in myocardial fatty acid and glucose use may lead to impaired efficiency that results in heart failure. This study followed the changes in glucose and fatty acid metabolism that occur during the progression of hypertrophy in the spontaneously hypertensive rat (SHR).

Methods: PET Studies. Dynamic PET data were acquired using the microPET II. A normotensive Wistar Kyoto (WKY) rat and a SHR were imaged at 10-week intervals. For each imaging session, 1-2mCi of ¹⁸FDG was injected and gated list mode data of 600-900 million counts were acquired over 60-80min. List mode data were histogrammed into dynamic sequences (42frames over 80min) including only the diastolic phase of the cardiac cycle. Dynamic sequences of 128×128×83 matrices of 0.4×0.4×0.582mm³ voxels in x, y, and z were reconstructed from 1203 140×210 sinograms using an iterative MAP reconstruction. Time activity curves were generated for the blood and left ventricular tissue regions of interest, and estimates of kinetic parameters were obtained by fitting the time activity curves to a 2-compartment model. SPECT Studies. Pinhole collimators (1.5mm aperture) were mounted on a dual head GE Millennium VG3 Hawkeye SPECT system. The system geometry was calibrated using a three-point source phantom. The rats were anesthetized and positioned in a holder mounted on the patient bed. A dynamic acquisition was performed by injecting ¹²³I-BMIPP immediately after starting the data acquisition. The detectors rotated continuously collecting 1s frames traversing 360^o every 90s for a total of 36 rotations. A MAP algorithm with geometric response modeling was used to reconstruct a sum of the dynamically acquired projections.

Results: The metabolic rate of FDG decreased with age for both the SHR and WKY rats but remained considerably higher for the SHR than for the normotensive WKY rat. The uptake of ¹²³I-BMIPP was greater in the normotensive WKY rats than in the hypertensive SHRs.

Conclusions: In the case of hypertension, there is an increased reliance on carbohydrate oxidation and reduced reliance on fatty acid metabolism, whereas the reverse is true for normotensive WKY rats. This may be indicative of maladaptation of cardiac metabolism to maintain cardiac function in the hypertrophied heart.

Research Support (if any): NIH R01-EB00121, R01-HL50663, and U.S. Department of Energy DE-AC02-05CH11231. Brian Abeysekera at MDS Nordion helped supply the ¹²³I-BMIPP.