Ephedrine activates brown adipose tissue in lean but not obese humans.

AIMS/HYPOTHESIS: Brown adipose tissue (BAT) activation increases energy consumption and may help in the treatment of obesity. Cold exposure is the main physiological stimulus for BAT thermogenesis and the sympathetic nervous system, which innervates BAT, is essential in this process. However, cold-induced BAT activation is impaired in obese humans. To explore the therapeutic potential of BAT, it is essential to determine whether pharmacological agents can activate BAT. METHODS: We aimed to determine whether BAT can be activated in lean and obese humans after acute administration of an orally bioavailable sympathomimetic. In a randomised, double-blinded, crossover trial, we administered 2.5 mg/kg of oral ephedrine to nine lean (BMI 22 ± 1 kg/m²) and nine obese (BMI 36 ± 1 kg/m²) young men. On a separate day, a placebo was administered to the same participants. BAT activity was assessed by measuring glucose uptake with [¹8F]fluorodeoxyglucose and positron emission tomography-computed tomography imaging. RESULTS: BAT activity was increased by ephedrine compared with placebo in the lean, but unchanged in the obese, participants. The change in BAT activity after ephedrine compared with placebo was negatively correlated with various indices of body fatness. CONCLUSIONS/INTERPRETATION: BAT can be activated via acute, oral administration of the sympathomimetic ephedrine in lean, but not in obese humans.

Metabolic response of rectal cancer assessed by 18-FDG PET following chemoradiotherapy is prognostic for patient outcome.

BACKGROUND: Complete pathological response has proven prognostic benefits in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Sequential 18-FDG PET may be an early surrogate for pathological response to chemoradiotherapy. OBJECTIVES: The aim of this study was to identify whether metabolic response measured by FDG PET following chemoradiotherapy is prognostic for tumor recurrence and survival following neoadjuvant therapy and surgical treatment for primary rectal cancer. METHODS: Patients with primary rectal cancer treated by long-course neoadjuvant chemoradiotherapy followed by surgery had FDG PET performed before and 4 weeks after treatment, before surgical resection was performed. Retrospective chart review was undertaken for patient demographics, tumor staging, recurrence rates, and survival. RESULTS: : Between 2000 and 2007, 78 patients were identified (53 male, 25 female; median age, 64 y). After chemoradiotherapy, 37 patients (47%) had a complete metabolic response, 26 (33%) had a partial metabolic response, and 14 (18%) had no metabolic response as assessed by FDG PET (1 patient had missing data). However, only 4 patients (5%) had a complete pathological response. The median postoperative follow-up period was 3.1 years during which 14 patients (19%) had a recurrence: 2 local, 9 distant, and 3 with both local and distant. The estimated percentage without recurrence was 77% at 5 years (95% CI 66%-89%). There was an inverse relationship between FDG PET metabolic response and the incidence of recurrence within 3 years (P = .04). Kaplan-Meier analysis of FDG PET metabolic response and overall survival demonstrated a significant difference in survival among patients in the 3 arms: complete, partial, and no metabolic response (P = .04); the patients with complete metabolic response had the best prognosis. CONCLUSION: Complete or partial metabolic response on PET following neoadjuvant chemoradiotherapy and surgery predicts a lower local recurrence rate and improved survival compared with patients with no metabolic response. Metabolic response may be used to stratify prognosis in patients with rectal cancer.

18 F-FDG PET/CT influences management in patients with known or suspected pancreatic cancer.

BACKGROUND: The aims of this study were (i) to assess and validate the incremental information of positron emission tomography/computed tomography (PET/CT) over conventional staging investigations (CSI) and (ii) to assess the management impact of PET/CT in patients with known or suspected pancreatic cancer. METHODS: Between October 2007 and September 2008, 22 PET/CT scans were performed using a dedicated PET/CT scanner in 21 patients with known or suspected pancreatic cancer. Follow up was used to reconcile discordance between PET/CT and CSI. The pre-PET/CT management plan and/or intent were prospectively recorded in all scans. The post-PET/CT management plan was determined from the medical record and/or discussions with treating clinicians. The management impact of PET/CT was classified as high, medium, low or none defined using Australian and New Zealand Association of Physicians in Nuclear Medicine PET data collection project criteria. RESULTS: PET/CT and CSI were discordant in 14/22 (64%: 95% CI; 43-84%) scans. Of the 14 discordant scans, PET/CT assessment was correct in eight, conventional imaging in four and there was insufficient information in two. Overall, PET/CT management impact was classified as high (n= 6), medium (n= 3), low (n= 9) or none (n= 4). Significant changes in management (high or medium impact) were induced by PET/CT in 9/22 scans (41%: 95% CI; 20-62%) predominantly by correctly modifying the disease extent. CONCLUSION: PET/CT has an incremental benefit over CSI and has a significant impact on management in patients with known or suspected pancreatic cancer. PET/CT merits consideration as part of the non-invasive evaluation of patients with known or suspected pancreatic cancer.

Recombinant human thyroid-stimulating hormone (Thyrogen) in thyroid cancer follow up: experience at a single institution.

BACKGROUND: Recombinant human thyroid-stimulating hormone (Thyrogen; Genzyme Corporation, Cambridge, MA, USA) (rhTSH)-stimulated serum thyroglobulin (Tg) (stim-Tg) and (131)I whole-body scanning (WBS) have been reported to allow follow up of patients with thyroid cancer without the symptoms of thyroxine withdrawal and with equivalent diagnostic information to that obtained after thyroxine withdrawal. The aim of the study was to report results of rhTSH use at the Alfred Hospital, Melbourne, from 1999 to 2006 and in particular to examine the significance of detectable serum Tg after rhTSH in relation to thyroid cancer staging and to compare the sensitivity of rhTSH-stimulated serum Tg to whole-body (131)I scanning (WBS) in the detection of residual and recurrent thyroid cancer. METHODS: The study was a retrospective chart review. RESULTS: In 90 patients, rhTSH was used for 96 diagnostic episodes and 18 doses of rhTSH were used to facilitate treatment with (131)I. In stages I and II cancer (n = 42), of three patients with stim-Tg 1-2 microg/L, none had identifiable disease, and the three patients who had stim-Tg >2 microg/L did not experience recurrent disease during follow up. In contrast, in stages III and IV cancer (n = 43) 2 of 5 with stim-Tg 1-2 microg/L had identifiable disease and 7 of 10 with stim-Tg >2 microg/L had identifiable disease. In Tg-positive, WBS-negative disease, further imaging identified persistent/recurrent disease. CONCLUSION: rhTSH was effective and safe in the management of thyroid cancer follow up for diagnosis of persistent/recurrent cancer and to enable (131)I treatment. In no case did rhTSH-stimulated WBS identify the presence of disease not also identified by raised basal Tg or stim-Tg. Therefore, in low risk cancer WBS may be omitted.

Evidence for regional catecholamine uptake and storage sites in the transplanted human heart by positron emission tomography.

Positron emission tomography in combination with the newly introduced catecholamine analogue [11C]hydroxyephedrine ([11C]HED) enables the noninvasive delineation of sympathetic nerve terminals of the heart. To address the ongoing controversy over possible reinnervation of the human transplant, 5 healthy control subjects and 11 patients were studied after cardiac transplant by this imaging approach. Regional [11C]HED retention was compared to regional blood flow as assessed by rubidium-82. Transplant patients were divided into two groups. Group I had recent (less than 1 yr, 4.4 +/- 2.3 mo) surgery, while group II patients underwent cardiac transplantation more than 2 yr before imaging (3.5 +/- 1.3 yr). [11C]HED retention paralleled blood flow in normals, but was homogeneously reduced in group I. In contrast, group II patients revealed heterogeneous [11C]HED retention, with increased uptake in the proximal anterior and septal wall. Quantitative evaluation of [11C]HED retention revealed a 70% reduction in group I and 59% reduction in group II patients (P less than 0.001). In group II patients, [11C]HED retention reached 60% of normal in the proximal anterior wall. These data suggest the presence of neuronal tissue in the transplanted human heart, which may reflect regional sympathetic reinnervation.

S-100B and FDG-PET/CT in therapy response assessment of melanoma patients.

OBJECTIVE: To compare the value of the tumor marker S-100B protein and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients treated for melanoma metastases. METHODS: In 41 patients with proven melanoma metastases, S-100B measurements and FDG-PET/CT were performed before and after therapy. The change of S-100B levels (DeltaS-100B) was assessed. In all patients, therapy response was assessed with PET/CT using visual criteria and change of maximal standard uptake value (DeltaSUV(max.)) or total lesion glycolysis (DeltaTLG). RESULTS: In 15 of 41 patients (37%), S-100B values were not suitable because they were normal before and after therapy. In 26 patients, S-100B was suitable for therapy response assessment. PET/CT was suitable for response assessment in all patients. Correlations between DeltaS-100B and DeltaTLG (r = 0.850, p < 0.001) and between DeltaS-100B and DeltaSUV(max.) (r = 0.818, p < 0.001) were both excellent. A complete agreement between S-100B and PET/CT response assessment was achieved in 22 of 26 patients. In 4 patients, therapy response differed between the S-100B and PET/CT findings, but subsequent S-100B measurements realigned the S-100B results with the later PET/CT findings. CONCLUSION: In a third of our patients with metastases, the S-100B tumor marker was not suitable for therapy assessment. In these patients, imaging techniques remain necessary, and FDG-PET/CT can be used for response assessment.

Clinical impact of (18)F fluorodeoxyglucose positron emission tomography in patients with non-small-cell lung cancer: a prospective study.

PURPOSE: To prospectively study the impact of (18)F fluorodeoxyglucose (FDG) positron emission tomography (PET) on clinical management of patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred five consecutive patients with NSCLC undergoing (18)F FDG PET were analyzed. Before PET, referring physicians recorded scan indication, conventional clinical stage, and proposed treatment plan. PET scan results were reported in conjunction with available clinical and imaging data, including results of computed tomography (CT). Subsequent management and appropriateness of PET-induced changes were assessed by follow-up for at least 6 months or until the patient's death. RESULTS: Indications for PET were primary staging (n = 59), restaging (n = 34), and suspected malignancy subsequently proven to be NSCLC (n = 12). In 27 (26%) of 105 of cases, PET results led to a change from curative to palliative therapy by upstaging disease extent. Validity of the PET result was established in all but one case. PET appropriately downstaged 10 of 16 patients initially planned for palliative therapy, allowing either potentially curative treatment (four patients) or no treatment (six patients). PET influenced the radiation delivery in 22 (65%) of 34 patients who subsequently received radical radiotherapy. Twelve patients considered probably inoperable on conventional imaging studies were downstaged by PET and underwent potentially curative surgery. PET missed only one primary tumor (5-mm scar carcinoma). CT and PET understaged three of 20 surgical patients (two with N1 lesions < 5 mm and one with unrecognized atrial involvement), and PET missed one small intrapulmonary metastasis apparent on CT. No pathological N2 disease was missed on PET. CONCLUSION: FDG PET scanning changed or influenced management decisions in 70 patients (67%) with NSCLC. Patients were frequently spared unnecessary treatment, and management was more appropriately targeted.

Quantitative evaluation of regional substrate metabolism in the human heart by positron emission tomography.

Meaning interpretation of metabolic images obtained by positron emission tomography for evaluation of cardiac disease requires a knowledge of the normal variation in regional myocardial substrate metabolism. Recent studies with fluorine-18 (F-18) fluorodeoxyglucose suggest inhomogeneity of myocardial glucose metabolism in the normal human heart, which may relate to substrate availability. Therefore, quantitative evaluation of myocardial oxidative metabolism and glucose metabolism, as derived by dynamic positron emission tomography with carbon-11 (C-11) acetate and F-18 fluorodeoxyglucose, was performed in nine healthy male volunteers. All were studied under tightly controlled metabolic conditions of hyperinsulinemic-euglycemic clamping with and without a concurrent lipid emulsion infusion. Significant inhomogeneity of regional glucose metabolism was noted although it was less than that described under fasting conditions. Glucose utilization was 13% lower in the septum compared with the lateral wall both without and with lipid infusion (0.34 vs. 0.39 mumol/g per min, respectively, p less than 0.05; and 0.33 vs. 0.38 mumol/g per min, respectively, (p less than 0.05). Relatively decreased septal glucose utilization could not be explained by decreased metabolic demand because C-11 clearance constants were marginally higher in the septum than in the lateral wall in both studies (0.055 vs. 0.054 per min, respectively, p = NS; and 0.061 vs. 0.056 per min, respectively, p less than 0.05). Relatively decreased septal glucose utilization could reflect regional variation in substrate use and possible preferential free fatty acid utilization by the septum. These data provide a useful framework for assessing altered cardiac metabolism in disease and support standardization of metabolic conditions during metabolic imaging with positron emission tomography.

Impact of radionuclide techniques on evaluation of patients with ischemic heart disease.

Radiotracer studies of the heart have become clinically important in the last decade, especially for evaluation of patients with known or suspected ischemic heart disease. Radionuclide ventriculography provides quantitative measures of biventricular function and regional wall motion. Recent technical advances include the development of computer programs for analyzing diastolic function, parametric imaging methods such as "phase" analysis and methods for calculating absolute ventricular volumes. Thallium-201 scans provide maps of regional myocardial perfusion. Recent advances include development of computer programs to quantitate regional thallium-201 uptake and to calculate thallium-201 turnover rates and the development of tomographic imaging systems. Technetium-99m pyrophosphate localizes in irreversibly damaged myocardium and provides a method for diagnosing, localizing and sizing acute myocardial infarcts. Recent applications include tomographic imaging to improve image contrast and development of criteria to identify high risk patients after infarction. Two important trends affecting the application of all the radionuclide studies in clinical cardiologic practice are the increasing use of decision analysis for incorporating results of multiple tests into single diagnostic probability statements, and the use of diagnostic algorithms that include the radionuclide studies to optimize the cost effectiveness of evaluation of patients with ischemic heart disease.

The spectrum of pheochromocytoma in hypertensive patients with neurofibromatosis.

We have found an appreciable number of pheochromocytomas in patients with neurofibromatosis and concurrent hypertension (ten of 18 cases). At diagnosis, the patient age range was 15 to 62 years, the clinical appearance of the neurofibromatosis did not predict who would and who would not have pheochromocytomas, but the age at diagnosis was helpful in that our younger patients tended to have causes of hypertension other than pheochromocytoma. However, several causes of hypertension may coexist. The biochemical findings were highly diagnostic. The pheochromocytomas secreted epinephrine as well as norepinephrine and resided in or next to the adrenal gland. Where pheochromocytoma is the cause of hypertension, its resection generally results in a better control of hypertension than that obtained in patients whose BPs were elevated from other unknown causes.

Evidence for increased noradrenaline release from subcortical brain regions in essential hypertension.

OBJECTIVE: To test whether the activation of the sympathetic nervous system that is common in essential hypertension derives from subcortical noradrenergic neuronal excitation. DESIGN AND METHODS: We performed a radionuclide cerebral venous sinus scan, using technetium-99m, to establish which internal jugular vein predominantly drained the cortical (the major jugular vein) and which the subcortical (minor jugular vein) brain regions. Blood samples were then collected simultaneously from catheters placed percutaneously in the brachial artery or radial artery and high in the internal jugular vein in 11 untreated hypertensive patients and 18 normotensive subjects, for determination of the plasma concentrations of noradrenaline, its precursor dihydroxyphenylalanine (DOPA) and its metabolite dihydroxyphenylglycol (DHPG) to calculate their rates of overflow into the cerebrovascular circulation. RESULTS: In normotensive subjects blood flow determined by thermodilution was significantly higher in the major than in the minor jugular vein. The noradrenaline spillovers into the major and minor jugular veins calculated during infusions of L-[3H]-7-noradrenaline were similar in healthy subjects. The noradrenaline spillover from subcortical regions into the minor jugular vein was significantly higher in the hypertensives than in the normal subjects, as was the overflow of DHPG. In contrast, cortical noradrenaline and DHPG overflows into the major jugular vein were similar in hypertensive and normotensive subjects. Overflow of DOPA into the minor jugular vein, which derives largely from precursor turnover in dopaminergic neurons, was similar in hypertensive and normotensive subjects. Subcortical noradrenaline spillover correlated with neurochemical indices of sympathetic nervous system activity, with total body noradrenaline spillover (r = 0.56, P < 0.05) in normal and hypertensive subjects combined, and with renal noradrenaline spillover in the six hypertensive patients tested (r = 0.91, P < 0.05). CONCLUSION: These results suggest that increased subcortical noradrenaline release is a possible cause of peripheral sympathetic activation in essential hypertension.

An assessment of factors which influence the effectiveness of the modified in vivo technetium-99m-erythrocyte labeling technique in clinical use.

This study assessed factors which may contribute to suboptimal image quality when the modified in vivo erythrocyte labeling technique is used with standard clinical 99mTc activities. For each assessment duplicate or triplicate blood specimens were withdrawn from > or = 10 patients, into syringes containing 700-900 MBq 99mTc as pertechnetate. After incubation the percent of 99mTc which was not bound to erythrocytes at blood re-injection time (%Unbound 99mTc), was measured and compared when one of four factors was varied. The most significant results, in descending order of measured effect were: [table: see text] Our data suggest that the requirements for optimal erythrocyte labeling with standard clinical 99mTc activities are: (A) Erythrocyte tinning time between 10 and 30 min; (B) blood volume > or = 3 ml; (C) blood incubation time > or = 20 min; and (D) Generator ingrowth time < or = 24 hr.

The relationship between myocardial blood flow and glucose uptake in ischemic canine myocardium determined with fluorine-18-deoxyglucose.

The relationship between myocardial blood flow as a marker of severity of ischemia and exogenous glucose utilization was examined following occlusion of the left anterior descending coronary artery in 10 fasted, anesthetized, open-chest dogs. Fluorine-18-fluorodeoxyglucose (FDG) was injected 10 min after the onset of ischemia and serial blood samples were obtained to measure FDG in plasma. Tracer-labeled microspheres, used to measure myocardial blood flow (MBF), were injected 10 and 40 min postocclusion. After the last microsphere injection, the heart was arrested and removed rapidly. Tissue samples of the left ventricle were obtained, weighed and FDG counts were determined. Two days later, the same samples were assayed for radioactivity from the tracer-labeled microspheres and blood flow was calculated. Thus, FDG uptake and MBF measurements were made in the same tissue samples. When normalized for variations in blood flow, there were no significant differences in FDG uptake between the subendocardial and subepicardial halves of the tissue samples. FDG uptake was relatively high and uniform in normal myocardium, paralleling the pattern of MBF. In ischemic myocardium, however, FDG uptake and MBF did not vary in parallel. In tissue samples with MBF reduced by up to 80% from control levels, relative FDG uptake increased such that absolute FDG uptake remained at normal or near normal levels. In samples with more severe ischemia, FDG uptake decreased precipitously with additional decrements in MBF. We propose that sufficient glycolytic flux may be sustained to maintain cellular viability when perfusion is above the threshold value. Below the threshold, however, irreversible changes may be initiated.

The normal and abnormal distribution of the adrenomedullary imaging agent m-[I-131]iodobenzylguanidine (I-131 MIBG) in man: evaluation by scintigraphy.

The scintigraphic distribution of m-[131I]iodobenzylguanidine (I-131 MIBG), an adrenal medullary imaging agent, was studied to determine the patterns of uptake of this agent in man. The normal distribution of I-131 MIBG includes clear portrayal of the salivary glands, liver, spleen, and urinary bladder. The heart, middle and lower lung zones, and colon were less frequently or less clearly seen. The upper lung zones and kidneys were seldom visualized. The thyroid appeared only in cases of inadequate thyroidal blockade. The "normal" adrenal glands were seldom seen and faintly imaged in 2% at 24 hr after injection and in 16% at 48 hr, in patients shown not to have pheochromocytomas, whereas intra-adrenal, extraadrenal, and malignant pheochromocytomas usually appeared as intense focal areas of I-131 MIBG uptake at 24 through 72 hr.

Scintigraphic demonstration of ventriculo atrial conduction in the ventricular pacemaker syndrome.

A patient with the sick-sinus syndrome was evaluated because of symptomatic deterioration after insertion of a ventricular demand pacemaker. Clinical features of the ventricular pacemaker syndrome were recognized and confirmed by electrophysiological and hemodynamic studies. Phase analysis--a new technique for detecting patterns of cardiac emptying from gated cardiac blood-pool scintigrams--demonstrated a pattern consistent with 1:1 ventriculo-atrial conduction. Phase analysis of the gated cardiac blood-pool scintigram may be useful in the assessment of patients with ventricular demand pacemakers who complain of fatigue and effort intolerance.

The utility of (18)F-FDG PET for suspected recurrent non-small cell lung cancer after potentially curative therapy: impact on management and prognostic stratification.

UNLABELLED: After potentially curative therapy of non-small cell lung cancer (NSCLC), masses or symptoms suggestive of relapse are common but may be difficult to characterize. Early detection is important because salvage therapies are available for localized recurrence. This study evaluated whether (18)F-FDG PET is useful and predictive of outcome in this setting. METHODS: For 63 consecutive patients with suspected relapse >6 mo after definitive treatment of NSCLC, the apparent extent of disease on conventional restaging was compared with that on FDG PET. Patients with already confirmed systemic metastases were excluded unless locally aggressive treatment of these was being considered. Serial imaging and pathologic results were obtained during a median follow-up of 19 mo to validate diagnostic findings. Prognostic significance was tested using the Cox proportional hazards regression model. RESULTS: PET had positive findings in 41 of 42 patients with confirmed relapse (sensitivity, 98%). No disease was evident during a minimum follow-up of 12 mo in 14 of 15 patients with clinically suspected relapse but negative PET findings (negative predictive value, 93%). PET induced a major management change in 40 patients (63%), including 6 whose treatment was changed from curative to palliative, 3 whose treatment was changed from palliative to curative, and 9 for whom negative PET findings prevented active management. Both the presence (P = 0.012) and the extent (P < 0.0001) of relapse on PET were highly significant prognostic factors. There was also significant prognostic stratification based on the treatment delivered after the PET study (P = 0.011), but after adjustment for this treatment, PET status remained highly predictive of survival. CONCLUSION: PET better assesses the status of disease and stratifies prognosis than does conventional staging, affects patient management, and should be incorporated into paradigms for suspected recurrence of NSCLC.

(18)F-FDG PET provides high-impact and powerful prognostic stratification in staging newly diagnosed non-small cell lung cancer.

UNLABELLED: Survival of lung cancer patients remains poor despite increasingly aggressive treatment. Conventional staging has well-described limitations. (18)F-FDG PET has been shown to stage lung cancer more accurately than does CT scanning, but the impact on patient treatment and outcome is poorly defined. This study evaluated this impact in routine clinical practice within a tertiary oncology facility. METHODS: For 153 consecutive patients with newly diagnosed non-small cell lung cancer, the treatment plan based on conventional staging methods was compared with the treatment plan based on incorporation of PET findings. Survival was analyzed using the Cox proportional hazards regression model. RESULTS: For broad groupings of stage, 10% of cases were downstaged and 33% upstaged by PET. When assessable, the PET stage was confirmed in 89% of patients. PET had a high impact on 54 patients (35%), including 34 whose therapy was changed from curative to palliative, 6 whose therapy was changed from palliative to curative, and 14 whose treatment modality was changed but not the treatment intent. For 39 patients (25%), a previously selected therapy was altered because of the PET findings. The Cox model indicated that the pre-PET stage was significantly associated with survival (P = 0.013) but that the post-PET stage provided much stronger prognostic stratification (P < 0.0001) and remained significant after adjustment for treatment delivered. CONCLUSION: Staging that incorporated PET provided a more accurate prognostic stratification than did staging based on conventional investigations. Further, the additional information provided by PET significantly and appropriately changed management in the majority of patients.

Radionuclide assessment of ventricular contraction at rest and during exercise following the Fontan procedure for either tricuspid atresia or single ventricle.

Ventricular contraction was evaluated in 18 patients studied at a mean of 2.6 years after Fontan repair. The diagnosis was tricuspid atresia in 9 patients and single ventricle in 9. Gated first-pass and gated equilibrium radionuclide ventriculography were performed at rest and during exercise. Abnormally low ventricular ejection fraction (EF) at rest was present in 8 of 18 patients by the gated equilibrium technique and 6 of 13 technically adequate gated first-pass studies. An abnormal response to exercise (failure of EF to increase less than or equal to 5% from rest to maximal exercise) was found in 10 of 16 patients by the gated equilibrium technique and in 8 of 12 by the gated first-pass technique. Only 2 patients by each radionuclide technique had both normal EF at rest and normal exercise response. Thus, this study confirms the frequent presence of abnormalities in ventricular contraction after the Fontan procedure at rest or during exercise or both despite absence of symptoms. Both EF response and the hemodynamic response during exercise were more abnormal in the presence of an atriopulmonary than an atrioventricular connection.

Use of carbon-11 acetate and dynamic positron emission tomography to assess regional myocardial oxygen consumption in patients with acute myocardial infarction receiving thrombolysis or coronary angioplasty.

Carbon-11 (C-11) acetate has been introduced for the noninvasive measurements of myocardial oxygen consumption. This study was designed to assess regional C-11 acetate clearance in patients with acute myocardial infarction. Thirty-one patients were studied within 8 days of acute myocardial infarction. C-11 acetate washout-rate constants were significantly lower in the infarct territory than in the remote myocardium (p < 0.008). The scintigraphic measurements correlated with heart rate-blood pressure product in the remote as well as infarct areas (0.52 and 0.48, respectively). There was no significant correlation to left ventricular ejection fraction. C-11 washout rates were significantly affected by beta-receptor therapy as assessed by multiple regression analysis. Thus, C-11 acetate kinetics allow noninvasive characterization of regional myocardial oxygen demand, which may be useful in assessing the extent of myocardial injury and myocardial oxygen demand of remote myocardium.

Assessment of right ventricular oxidative metabolism by positron emission tomography with C-11 acetate in aortic valve disease.

Evaluation of right ventricular (RV) oxidative metabolism is limited by the inability to easily determine oxygen extraction by the RV myocardium and the complex morphology of this ventricle. Because left ventricular C-11 clearance rate constants closely correlate with myocardial oxygen consumption, it was postulated that C-11 clearance rate constants for the RV free wall should also reflect its oxygen consumption. Therefore, RV C-11 clearance rate constants were compared with RV loading in 21 patients with aortic valve disease to assess the possible use of this technique for noninvasive evaluation of RV oxidative metabolism. RV free wall C-11 clearance rate constants correlated with the product of systolic pulmonary artery pressure and heart rate for all patients (r = 0.65, p = 0.002), but the relation was stronger if 2 patients with overt RV dysfunction were excluded (r = 0.83, p = 0.001). On the basis of mean pulmonary artery pressures, patients were stratified into subgroups with normal (group I, n = 8) and elevated (group II, n = 13) pulmonary pressures and were compared with 10 normal control subjects. RV C-11 clearance rate constants were significantly higher in group II than in group I and in normal control subjects (p less than 0.05). These data suggest that RV C-11 acetate clearance rate constants can provide noninvasive evaluation of RV oxidative metabolism. This technique may allow serial assessment of RV performance in various cardiac and pulmonary diseases, and particularly of changes associated with therapeutic interventions.