C. G. Rhodes

Preoperative prediction of the outcome of coronary revascularization using positron emission tomography.

BackgroundPrevious assessments of myocardial viability using positron emission tomography (PET) relied on demonstration of glucose metabolism in hypoperfused asynergic segments using the glucose analogue [18F]2-fluoro-2-deoxyglucose (FDG). Recently, it was shown that myocardial viability could be assessed by calculating the water-perfusable tissue index (PTI) for the asynergic region. PTI represents the proportion of the myocardium that is capable of rapid transsarcolemmal exchange of water and thus perfusable by water. The aim of the present study was to assess myocardial viability by PET using PTI in patients undergoing coronary revascularization. Methods and ResultsTwelve patients with chronic coronary artery disease and previous myocardial infarction were studied. Analysis of transmission (tissue density) and 15O-labeled carbon monoxide (blood pool), and 150-labeled water (myocardial blood flow [MBF]) emission PET data enabled the simultaneous quantification of MBF (ml · min−1 · g perfusable tissue−1) and PTI (gram of perfusable tissue per gram of total anatomic tissue). In addition, PET imaging with FDG after 75-g oral glucose load was performed in eight patients. Preoperative echocardiography identified 33 hypocontractile and 26 control segments. Follow-up echocardiography performed 3 to 5 months later demonstrated 26 of 33 segments with improved wall motion (recovery) and seven of 33 segments without improvement (nonrecovery). MBF in the control segments (0.97 ± 0.22 ml · min−1 · g perfusable tissue−1) was significantly higher (p < 0.001) than in both the recovery (0.73 ± 0.18 ml min−1 g perfusable tissue−1) and the nonrecovery (0.45 ± 0.11 ml min−1 · g perfusable tissue−1) segments. PTI in the recovery regions (0.99 ± 0.15) was≥0.7 in all cases and slightly less than in control regions (1.10 ± 0.15, p < 0.02). FDG uptake in these regions was 92 ± 17% (n=13) of the uptake in control segments with normal wall motion. In the nonrecovery group, PTI was 0.62 ± 0.06 (p < 0.02 versus control and recovery) and always < 0.7. In the one patient in whom a comparison with metabolic imaging was made, FDG uptake was 46% of the uptake in a reference region with normal wall motion. ConclusionsThese data showed that contractile recovery occurred only in segments where PTI was ≥0.7, suggesting that ≥70% of myocardial tissue in a given asynergic segment should be perfusable by water to enable contractile recovery. There was good agreement between the PTI and FDG methods for predicting improvements in regional wall motion after revascularization. Although further studies should be performed in a larger patient group, the preliminary results are promising and suggest that PTI may be a good predictor of contractile recovery after coronary revascularization.

Enhanced myocardial 18F-2-fluoro-2-deoxyglucose uptake after orthotopic heart transplantation assessed by positron emission tomography.

OBJECTIVESnWe sought to assess the relation between glucose metabolism, myocardial perfusion and cardiac work after orthotopic heart transplantation.nnnBACKGROUNDnThe metabolic profile of the transplanted cardiac muscle is affected by the lack of sympathetic innervation, impaired inotropic function, chronic vasculopathy, allograft rejection and immunosuppressive therapy. In relation to myocardial perfusion and cardiac work, glucose metabolism has not previously been studied in heart transplant recipients.nnnMETHODSnRegional myocardial blood flow (ml.min-1.g-1) and 18F-2-fluoro-2-deoxyglucose (18FDG) uptake rate (ml.s-1.g-1) were measured after an overnight fast in 9 healthy male volunteers (mean age +/- SD 32 +/- 7 years) and in 10 male patients (mean age 50 +/- 10 years) who had a nonrejecting heart transplant, normal left ventricular function and no angiographic evidence of epicardial coronary sclerosis. Measurements were made by using dynamic positron emission tomography (PET) with 15O-labeled water and 18FDG, respectively. Heart rate and blood pressure were also measured for calculation of rate-pressure product.nnnRESULTSn18FDG uptake was similar in all heart regions in the patients and volunteers (intrasubject regional variably 12 +/- 8% and 16 +/- 12%, respectively, p = 0.51). Regional myocardial blood flow was similarly evenly distributed (intrasubject regional variability 14 +/- 10% and 12 +/- 8%, respectively, p = 0.67). Mean 18FDG uptake and myocardial blood flow values for the whole heart are given because no regional differences were identified. 18FDG uptake was on average 196% higher in the patients than in the volunteers (2.90 +/- 1.79 x 10(-4) vs. 0.98 +/- 0.38 x 10(-4) ml.s-1.g-1, p = 0.006). Regional myocardial blood flow and rate-pressure product were similarly increased in the patient group, but by only 41% (1.14 +/- 0.3 vs. 0.81 +/- 0.13 ml.min-1.g-1, p = 0.008) and 53% (11,740 +/- 2,830 vs. 7,689 +/- 1,488, p = 0.001), respectively.nnnCONCLUSIONSn18FDG uptake is homogeneously increased in normally functioning nonrejecting heart transplants. This finding suggests that glucose may be a preferred substrate in the transplanted heart. The magnitude of this observed increase is significantly greater than that observed for myocardial blood flow or cardiac work. In the patient group, the latter two variables were increased to a similar degree over values in control hearts, indicating a coupling between cardiac work load and myocardial blood flow. The disproportionate rise in 18FDG uptake may be accounted for by inefficient metabolic utilization of glucose by the transplanted myocardium or by the influence of circulating catecholamines, which may stimulate glucose uptake independently of changes in cardiac work load.

Effect of long-term β2-agonist dosing on human cardiac β-adrenoceptor expression in vivo: Comparison with changes in lung and mononuclear leukocyte β-receptors

BackgroundTachyphylaxis to the cardiac effects of β-adrenoceptor stimulation after long-term β2-agonist administration is well recognized, but the influence on global cardiac β-adrenoceptor density has not been previously investigated in vivo. Positron emission tomography (PET) has made possible the noninvasive quantification of regional receptor density. This study assesses the effect of long-term β2-agonist dosing on cardiac β-adrenoceptors.Methods and Resultsβ-Adrenoceptors in the hearts of 29 healthy male subjects aged 35±8 years were imaged and quantified in vivo by means of PET and compared with the receptor density in the same subjects’ lung tissue. Mononuclear leukocyte (MNL) β-receptor density was determined in vitro by means of a radioligand binding assay. β-Receptor density was 8.41±2.03 pmol/gm tissue in heart, 10.81±1.91 pmol/gm tissue in lung, and 38.0±17.5 fmol/mg protein on MNLs. There was a weak relationship between cardiac and pulmonary β-receptor densities (r=0.45, p<0.02) but not between cardiac and MNL receptor density. In seven subjects, the measurements were repeated after 2 weeks of albuterol treatment (4 mg orally twice daily and 200 μg inhaled four times daily in the first week, with doubling of the dose during the second week). After the albuterol treatment, β-receptor density fell on average by 19% (p<0.05) in the heart compared with 22% (p<0.05) in the lung and 42% (p<0.05) in MNLs. Correlations were found between the percentage changes in receptor density in heart and lung (r=0.98, p<0.001) and in heart and MNLs (r=0.99, p<0.002).ConclusionsTwo weeks of high-dose albuterol results in equivalent downregulation of β-receptors in vivo, both in the lung and in the heart.

Reduced beta adrenoceptor density in vivo in human lung tumours: a preliminary study with positron emission tomography.

BACKGROUND: Reduced beta adrenergic receptor density in tumours has been reported in previous in vitro studies. The aim of the present study was to assess whether this occurs in vivo. METHODS: Pulmonary beta adrenoceptors were imaged and quantified in vivo using positron emission tomography (PET) and the beta antagonist radioligand (S)-[11C]CGP-12177 in five men with lung tumours of mean age 58 years (range 42-68). The histology of the tumours was squamous cell carcinoma in two cases, adenocarcinoma in one, carcinoid tumour in one, and large cell carcinoma in one. The regional blood volume and extravascular tissue density were also measured using PET. Regions of interest were drawn for both non-tumour and tumour lung tissue. RESULTS: The mean (SD) blood volume was 0.142 (0.025) ml/ml in tumour regions and 0.108 (0.010) ml/ml in normal lung regions--a difference of 31%. Mean (SD) extravascular tissue density was 0.653 (0.133) g/ml in tumour regions, substantially higher than in normal lung regions (0.157 (0.021) g/ml). On the contrary, beta receptor density was 5.1 (1.8) pmol/g in tumour regions, lower than the value of 9.9 (1.6) pmol/g found in adjacent normal lung--a difference of 48%. CONCLUSIONS: In vivo beta adrenoceptor density is reduced in human lung tumours.