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Simultaneous PET and NMR—initial results from isolated, perfused rat hearts

Department of Radiological Sciences, Guy's, King's and St Thomas' School of Medicine, Guy's Campus, London SE1 9RT, UK

View larger version (19K): [in a new window]   Figure 1. 31P NMR spectrum of an isolated, perfused rat heart. Peaks are as labelled.

View larger version (31K): [in a new window]   Figure 2. Cross-sectional diagram showing the mini-PET scanner and its associated electronics and, within the large circle, an enlarged view of the heart, the NMR probe and the mini-PET scanner.

View larger version (27K): [in a new window]   Figure 3. 18FDG PET scans and 31P NMR spectra (obtained simultaneously) of an isolated, perfused rat heart after 85, 115, 145 and 175 min of perfusion. Workload was constant for the first three scans and spectra and was increased by 20% prior to the final acquisitions.

View larger version (13K): [in a new window]   Figure 4. Effect of lactate on the accumulation of FDG6P in rat hearts (determined by PET). Hearts were perfused with Krebs buffer plus 11 mM glucose (plus 125 MBq tracer 18FDG) for the first 100 min and subsequently perfused with Krebs buffer plus 11 mM glucose plus 10 mM lactate (plus 125MBq tracer 18FDG). Values are mean±SEM and are expressed in counts per second (cps), n=4 per group.

View larger version (15K): [in a new window]   Figure 5. Effect of lactate on the accumulation of DG6P in rat hearts (determined by 31P NMR). DG6P is measured in arbitrary units calculated with Bruker software after scaling all spectra to a reference spectrum. Filled circles, hearts perfused with Krebs buffer plus 11 mM glucose; open circles, hearts perfused with Krebs buffer plus 11 mM glucose plus 10 mM lactate. Values are mean±SEM, *p<0.05 compared with Krebs buffer plus glucose hearts, n=4 per group.

View larger version (24K): [in a new window]   Figure 6. Diagram showing the relative sub-cellular distribution of the GLUT1 and GLUT4 glucose transporters in the heart during perfusion with glucose as the sole substrate.

View larger version (11K): [in a new window]   Figure 7. Effect of lactate on the distribution of GLUT1 and GLUT4 in perfused hearts. Histograms show the percentage of the transporters in the plasma membrane. Values are given as mean±SEM, *p<0.05 compared with glucose-only hearts, n=5 per group.

View larger version (40K): [in a new window]   Figure 8. Diagram of the top section of the two surface-coil NMR probe for the dual-perfusion system showing the positioning of the coils, the PET scanner crystal array and the perfused heart. The cannula is sealed at the end and the buffer flows out of the two oval holes (which subtend an angle of 170°) directly into the two coronary ostia.

View larger version (13K): [in a new window]   Figure 9. Perfusion protocol for the regional ischaemia–reperfusion experiments. The orange arrows indicate times at which NMR spectra were acquired from the control side of the heart and the grey arrows indicate times at which NMR spectra were acquired from the ischaemic side. The black arrows indicate the times at which PET scans were acquired.

View larger version (58K): [in a new window]   Figure 10. (a) Representative FDG PET scans obtained during pre-ischaemia (45 min), regional ischaemia (40 min) and reperfusion (60 min). (b) Regions of interest superimposed on a midventricular PET scan. (c) Photograph of mid-ventricular slice through the heart after perfusion with blue dye.

View larger version (24K): [in a new window]   Figure 11. FDG uptake data, plotted as % of initial counts, against time. Filled squares: the ischaemic-reperfused side of the heart. Open squares: the control side of the heart. The data are plotted as the mean±SEM, *p<0.05, **p<0.01, n=5 per group.

View larger version (19K): [in a new window]   Figure 12. (a) and (b) 31P NMR spectra obtained pre-ischaemia; (c) spectrum obtained from control left ventricle during ischaemia of right ventricle; (d) spectrum obtained from ischaemic right ventricle and septum; (e) and (f) spectra obtained during reperfusion. Spectra from the control side of the heart are shown on the left. Exact times at which spectra were acquired are as marked. The peaks are as labelled.

View larger version (15K): [in a new window]   Figure 13. Accumulation of DG6P, plotted as normalized arbitrary units against time, during reperfusion. Sold squares: ischaemic-reperfused side. Open circles: the control side of the heart. The data are plotted as mean+SEM.

View larger version (14K): [in a new window]   Figure 14. Effect of ischaemia–reperfusion on the distribution of GLUT1 and GLUT4 in perfused hearts. Histograms show the percentage of the transporters in the plasma membrane. Values are given as mean±SEM, *p<0.05 compared with control hearts, n=5 per group.