 |
Metabolic conditions stimulating FDG uptake in the heartProfessor Paolo G. Camici Background  Figure 1. PET images of the chest of a patient with stable angina. In each image the left ventricle free wall is in the 6 to 10 o’clock position, the anterior wall and septum are in the 10 to 3 o’clock position, and the remaining open area is the plane of the mitral valve. Myocardial uptake of rubidium-82 (RB) at rest (top left) is homogeneous, while during exercise (top right), cation uptake is severely reduced in the anterior wall. When FDG was injected at rest (bottom left) after overnight fasting, myocardial tracer uptake was very low, the heart profile being barely detectable. In this patient FDG was also injected during recovery from the stress test when all signs of ischaemia had disappeared. Under these conditions (bottom right) the region of previous ischaemia was clearly identifiable, tracer uptake in the anterior wall being 1.75 times higher than that in non-ischaemic myocardium. Under these circumstances, patients are not distinguishable from normal volunteers studied under the same conditions.[4] To study the effects of exercise on myocardial metabolism, patients with effort angina were subjected to maximal bicycle ergometric exercise in the supine position within a PET camera. In all patients the stress test induced typical chest pain and ECG signs of ischaemia that were accompanied by regional abnormalities of perfusion. An increase in myocardial glucose utilization was observed during the stress test. This increase, however, was not regionally homogeneous: glucose utilization in the non-ischaemic areas (i.e. those showing an increase in perfusion during exercise comparable with that in normal subjects) increased more than in the ischaemic regions (i.e. those developing flow defects during exercise), even though FDG uptake in the ischaemic zone was in excess of perfusion (Figure 2).[5]  Figure 2. PET images of rubidium-82 (RB) and FDG uptake in the left ventricle of a patient with stable angina. Myocardial uptake of RB at rest (top left) is homogeneous, while during exercise (top right), cation uptake is severely reduced in the anteroseptal myocardium. When FDG was injected during the exercise (bottom left), tracer concentration in the ischaemic region was 0.75 times lower than in the non-ischaemic tissue (free wall) even though FDG in the ischaemic zone was in excess of perfusion. The scan recorded following an injection of FDG in the recovery phase, when RB had normalized (bottom right), shows a higher (1.90 times) tracer concentration in the previously ischaemic region in comparison with the non-ischaemic tissue (free wall). For figure orientation see legend to Figure 1. Post-ischaemic FDG uptake When glucose utilization is measured in the recovery period after exercise when all the indices of ischaemia, including myocardial perfusion, have normalized, a persistently increased FDG uptake can be demonstrated in the post-ischaemic myocardium (Figure 2). Taking enhanced FDG uptake as a sign of metabolic ischaemia, this post-exercise change could be termed a persistent metabolic abnormality that apparently occurs in the absence of symptoms or signs of frank ischaemia. The increased glucose uptake is not sustained by ischaemia, since coronary flow was comparable to that of control values, and could reflect either an increased glycolytic flux and/or an increased rate of glycogen synthesis due to depletion of the polysaccharide induced by ischaemia. The latter hypothesis is supported by experiments performed in the isolated perfused working rat heart where glycogen breakdown and synthesis were measured before and after a period of total global ischaemia.6 In addition, preliminary results obtained with 11C-glucose and PET in patients with stable angina who showed increased uptake of FDG in the post-ischaemic myocardium, seem further to support the above hypothesis.[5] FDG uptake in patients with unstable angina pectoris Patients with unstable angina, characterized by frequent repeated episodes of spontaneous ST-segment depression, without evidence of acute infarction, were studied using FDG and PET after an overnight fast, at rest, and in the absence of symptoms and signs of myocardial ischaemia at the time of PET.[7] Myocardial FDG uptake in these patients was different from that observed in normals and patients with stable angina. In fact, FDG uptake was regionally or globally increased (Figure 3).
This change occurred most often in the absence of perfusion abnormalities. It might be hypothesized that this pattern of FDG uptake represents a chronic adaptation of myocardial metabolism to repetitive ischaemia. The validity of the latter hypothesis was, at least in part, confirmed by further studies in these patients which proved that reduction of the number of ischaemic episodes, achieved by intensive medical treatment, was associated with normalization of the pattern of myocardial FDG uptake.[8–10] REFERENCES |
Figure
3. Myocardial (septal, anterior and free wall of the left
ventricle) and skeletal muscle glucose uptake were measured using
FDG and PET in normal volunteers and patients with stable or unstable
angina, at rest and after overnight fasting. Glucose uptake was
similarly low in normal subjects and patients with stable angina,
but was significantly increased in patients with unstable angina
despite the absence of symptoms and signs of myocardial ischaemia
at the time of PET. It should be noted that the increase in FDG
uptake was confined to the heart, as shown by the similar uptake
in skeletal muscle in the three groups. This suggests that local,
rather than systemic mechanisms, are likely to be responsible
for the increased glucose utilization in patients with unstable
angina (LC = 1).the publisher or the sponsor is not responsible for the continued currency of the information,
for any errors or omissions, or for any consequence arising therefrom.
© 2010 Les Laboratoires Servier