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PURPOSE: Methyl-(11)C-choline ([(11)C]choline) is a radiopharmaceutical used for oncological PET studies. We investigated the biodistribution and biokinetics of [(11)C]choline and provide estimates of radiation doses in humans. METHODS: The distribution of [(11)C]choline was evaluated ex vivo in healthy rats (n=9) by measuring the radioactivity of excised organs, and in vivo in tumour-bearing rats (n=4) by PET. In addition to estimates of human radiation doses extrapolated from rat data, more accurate human radiation doses were calculated on the basis of PET imaging of patients with rheumatoid arthritis (n=6) primarily participating in a synovitis imaging project with [(11)C]choline. Dynamic data were acquired from the thorax and abdomen after injection of 423+/-11 MBq (mean+/-SD) of tracer. Following PET imaging, the radioactivity in voided urine was measured. The experimental human data were used for residence time estimations. Radiation doses were calculated with OLINDA/EXM. RESULTS: In rats, the radioactivity distributed mainly to the kidneys, lungs, liver and adrenal gland. The effective dose in a human adult of about 70 kg was 0.0044 mSv/MBq, which is equivalent to 2.0 mSv from 460 MBq of [(11)C]choline PET. The highest absorbed doses in humans were 0.021 mGy/MBq in the kidneys, 0.020 mGy/MBq in the liver and 0.029 mGy/MBq in the pancreas. Only 2.0% of injected radioactivity was excreted in the urine during the 1.5 h after injection. CONCLUSION: The absorbed radiation doses after administration of 460 MBq of [(11)C]choline were low. Except for the pancreas, biodistribution in the rat was in accordance with that in humans, but rat data may underestimate the effective dose, suggesting that clinical measurements are needed for a more detailed estimation. The observed effective doses suggest the feasibility of [(11)C]choline PET for human studies.
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Colina/análogos & derivados , Radiometría/métodos , Adulto , Animales , Colina/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Dosis de Radiación , Radiofármacos/farmacocinética , RatasRESUMEN
OBJECTIVE: Breast cancer is one of the principal oncological challenges in the Western world. Currently, there are only a few reliable predictive methods for monitoring treatment. We investigated the ability of carbon-11 methionine ("11C-MET) positron emission tomography (PET) to evaluate early response to therapy in advanced breast cancer. METHODS: Thirteen patients with metastases in the lungs/pleura, lymph nodes, soft tissue, or bones entered a MET PET study both before and after the first cycle of polychemotherapy (n=4), or after the first month of therapy with hormones (n=5), or low dose weekly cytostatics (n=3). One patient underwent three PET studies: before hormonal therapy, after 1 month of hormonal therapy, and after the first cycle of polychemotherapy (total, 27 studies). MET accumulation in the metastatic sites was measured as standardized uptake values (SUVs), and the pretreatment and post-treatment SUVs were compared with each other and the clinical follow-up data. RESULTS: A total of 26 different metastatic sites were investigated in 13 patients. All metastases were visible by MET PET except one superficially spreading local skin recurrence, probably because of respiratory movements. Five new metastatic sites were detected. After therapy the SUVs decreased significantly (30-54%; P < 0.05) in all six responding metastatic sites, whereas the SUVs of nonresponding metastases decreased somewhat (11-130/%; n=4), remained stable (+/- 8%; n=10), or increased (13-23%; n=4) (P=NS). The SUVs of two nonresponding metastatic sites decreased clearly. Physiological MET uptake in the salivary glands, the myocardium, and the bone marrow did not disturb the image interpretation. CONCLUSION: MET PET may be useful in assessing the early response to therapy in advanced breast cancer.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia , Metionina , Adulto , Anciano , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , Masculino , Metionina/metabolismo , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/secundario , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of this study was to determine the effect of exercise training on myocardial oxidative metabolism and efficiency in patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (HF). BACKGROUND: Exercise training is known to improve exercise tolerance and quality of life in patients with chronic HF. However, little is known about how exercise training may influence myocardial energetics. METHODS: Twenty clinically stable patients with DCM (New York Heart Association classes I through III) were prospectively separated into a training group (five-month training program; n = 9) and a non-trained control group (n = 11). Oxidative metabolism in both the right and left ventricles (RV and LV) was measured using [(11)C]acetate and positron emission tomography. Myocardial work power was measured using echocardiography. Myocardial efficiency for forward work was calculated as myocardial work power per mass/LV oxidative metabolism. RESULTS: Significant improvements were noted in exercise capacity (VO(2)) and ejection fraction in the training group, whereas no changes were observed in the non-trained group. Exercise training reduced both RV and LV oxidative metabolism and elicited a significant increase in LV forward work efficiency, although no significant changes were observed in the non-trained group. CONCLUSIONS: Exercise training improves exercise tolerance and LV function. This is accompanied by a decrease in biventricular oxidative metabolism and enhanced forward work efficiency. Therefore, exercise training elicits an energetically favorable improvement in myocardial function and exercise tolerance in patients with DCM.
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Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/terapia , Metabolismo Energético/fisiología , Terapia por Ejercicio , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/terapia , Ventrículos Cardíacos/metabolismo , Disfunción Ventricular Izquierda/metabolismo , Disfunción Ventricular Izquierda/terapia , Adulto , Cardiomiopatía Dilatada/diagnóstico , Ecocardiografía , Femenino , Insuficiencia Cardíaca/diagnóstico , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Tomografía Computarizada de Emisión , Disfunción Ventricular Izquierda/diagnósticoRESUMEN
PURPOSE: This study was conducted to develop a new positron emission tomography (PET) method to visualize neurokinin-1 (NK(1)) receptor systems in the human brain in vivo in order to examine their neuroanatomical distribution and facilitate investigations of the role of substance P, NK(1) receptors, and NK(1) receptor antagonists in central nervous system (CNS) function and dysfunction. METHODS: PET studies were conducted in 10 healthy male volunteers using a novel selective, high-affinity NK(1) receptor antagonist labeled with fluorine-18 to very high specific radioactivity (up to 2000 GBq/micromol) [F-18]SPA-RQ. Data were collected in 3D mode for greatest sensitivity. Different modeling methods were compared and regional receptor distributions determined for comparison with in vitro autoradiographic studies using postmortem human brain slices with [F-18]SPA-RQ. RESULTS: The studies showed that the highest uptake of [F-18]SPA-RQ was observed in the caudate and putamen. Lower binding was found in globus pallidus and substantia nigra. [F-18]SPA-RQ uptake was also widespread throughout the neocortex and limbic cortex including amygdala and hippocampus. There was very low specific uptake of the tracer in the cerebellar cortex. The distribution pattern was confirmed using in vitro receptor autoradiography with [F-18]SPA-RQ on postmortem human brain slices. Kinetic modeling of the [F-18]SPA-RQ uptake data indicated a binding potential between 4 and 5 in the basal ganglia and between 1.5 and 2.5 in the cortical regions. CONCLUSIONS: [F-18]SPA-RQ is a novel tool for exploration of the functions of NK(1) receptors in man. [F-18]SPA-RQ can be used to define receptor pharmacodynamics and focus dose selection of novel NK(1) receptor antagonists in clinical trials thereby ensuring adequate proof of concept testing particularly in therapeutic applications related to CNS dysfunction.
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Encéfalo/metabolismo , Receptores de Neuroquinina-1/análisis , Receptores de Neuroquinina-1/metabolismo , Adulto , Arterias/metabolismo , Autorradiografía , Ganglios Basales/metabolismo , Encéfalo/anatomía & histología , Radioisótopos de Flúor/farmacocinética , Humanos , Cinética , Masculino , Mesencéfalo/anatomía & histología , Mesencéfalo/metabolismo , Modelos Biológicos , Antagonistas del Receptor de Neuroquinina-1 , Estándares de Referencia , Cráneo/metabolismo , Factores de Tiempo , Distribución TisularRESUMEN
UNLABELLED: Abnormalities of autonomic nervous function are associated with a poor prognosis of patients with chronic heart failure (CHF). We studied the effects of a 6-mo exercise training program on Q-T interval dispersion, heart rate and blood pressure variability, baroreflex sensitivity, myocardial blood flow (MBF), and presynaptic sympathetic innervation in 13 patients with New York Heart Association class II-III heart failure. METHODS: MBF was measured with the H(2)(15)O and C(15)O technique. Cardiac presynaptic innervation was studied by (11)C-hydroxyephedrine (HED) retention assessed with PET. Heart rate and blood pressure variability and baroreflex sensitivity were tested with the phenylephrine method. All studies were performed before and after a 6-mo exercise training program. The exercise capacity was determined by spiroergometry, and Q-T dispersion was measured from a standard 12-lead electrocardiogram. RESULTS: Q-T dispersion was reduced after the training period (mean +/- SEM, from 52 +/- 5 to 36 +/- 5 ms [P = 0.01]). Global (11)C-HED retention improved from 0.228 +/- 0.099 to 0.263 +/- 0.066 s(-1) (P < 0.05). Global MBF was not affected by training, but MBF increased in areas of low initial perfusion in patients with coronary artery disease (from 0.382 +/- 0.062 to 0.562 +/- 0.083 mL/g/min [P < 0.005]). The high-frequency spectrum and total R-R interval variability increased (from 4.53 +/- 0.30 to 5.02 +/- 0.36 ms(2) [P < 0.05] and from 3.60 +/- 0.34 to 4.31 +/- 0.37 ms(2) [P < 0.005], respectively). Both changes correlated significantly with the observed change in (11)C-HED retention. There was a significant reduction of total and a near-significant reduction of low-frequency (LF) systolic blood-pressure (SBP) variability (from 4.89 +/- 1.03 to 3.18 +/- 0.48 [P < 0.05] and from 2.79 +/- 0.38 to 1.76 +/- 0.24 [P = 0.059], respectively). The decrease in LF SBP variability correlated inversely with the enhancement of (11)C-HED retention (r = -0.66; P < 0.05). Baroreflex sensitivity increased from 5.83 +/- 0.82 to 10.15 +/- 1.66 ms/mm Hg (P < 0.05). CONCLUSION: Exercise training induces beneficial changes in functional and imaging measures of cardiovascular autonomic nervous control. These observations point to a training-induced shift toward normalization of the compensatory autonomic nervous imbalance in CHF.
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Sistema Nervioso Autónomo/fisiología , Terapia por Ejercicio , Insuficiencia Cardíaca/rehabilitación , Corazón/diagnóstico por imagen , Tomografía Computarizada de Emisión , Radioisótopos de Carbono , Electrocardiografía , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To develop and characterize a radiolabelled Substance-P antagonist useful for quantitation of neurokinin-1 receptors in the brain via PET imaging. PROCEDURE: [18F]SPA-RQ (Substance-P antagonist - receptor quantifier) was synthesized in good yield and high specific activity by alkylation of a BOC protected phenolate anion using [18F]bromofluoromethane. Removal of the BOC protecting group with trifluoroacetic acid gave [18F]SPA-RQ. RESULTS: SPA-RQ has high affinity for human, rhesus monkey and guinea pig NK1 receptors (h-IC50=67 pM) and has a log P value of 1.8. Biodistribution studies in guinea pig showed that this tracer penetrates the blood-brain barrier and selectively labels NK1 receptors in the striatum and cortex. CONCLUSION: [18F]SPA-RQ is a potent, high affinity Substance-P antagonist that can be conveniently labeled with high specific activity using [18F]fluoromethylbromide. This tracer is a useful tool for noninvasive imaging of central NK1 receptors.
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Encéfalo/diagnóstico por imagen , Receptores de Neuroquinina-1/análisis , Sustancia P/antagonistas & inhibidores , Animales , Encéfalo/metabolismo , Radioisótopos de Flúor , Cobayas , Humanos , Hidrocarburos Bromados/síntesis química , Hidrocarburos Bromados/química , Hidrocarburos Bromados/metabolismo , Hidrocarburos Fluorados/síntesis química , Hidrocarburos Fluorados/química , Hidrocarburos Fluorados/metabolismo , Macaca mulatta , Masculino , Estructura Molecular , Tomografía de Emisión de Positrones , Receptores de Neuroquinina-1/metabolismo , Sensibilidad y Especificidad , Análisis Espectral , Distribución TisularRESUMEN
(1R,2S)-4-[18F]fluorometaraminol (4-[18F]FMR), a tracer for cardiac sympathetic innervation, was synthesized by electrophilic aromatic substitution. A trimethylstannyl precursor, protected with tert-butoxycarbonyl protecting groups, was radiofluorinated with high specific radioactivity [18F]F2. Specific radioactivity of 4-[18F]FMR, in average 11.8 +/-3.3 GBq/micromol, was improved 40-800-fold in comparison to the previous electrophilic fluorinations. The biodistribution of 4-[18F]FMR in rat was in accordance with the known distribution of sympathetic innervation. 4-[18F]FMR showed no metabolic degradation in left ventricle of rat heart, where the uptake was high, rapid and specific.
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Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/metabolismo , Metaraminol/análogos & derivados , Metaraminol/farmacocinética , Norepinefrina/metabolismo , Sistema Nervioso Simpático/diagnóstico por imagen , Sistema Nervioso Simpático/metabolismo , Animales , Biotransformación , Carga Corporal (Radioterapia) , Electroquímica/métodos , Ventrículos Cardíacos/inervación , Marcaje Isotópico/métodos , Masculino , Metaraminol/síntesis química , Especificidad de Órganos , Dosis de Radiación , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Tomografía Computarizada de Emisión/métodosRESUMEN
PURPOSE: The aim of the study was to compare (68)Ga-chloride with 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) for the imaging of pancreatic xenografts. PROCEDURES: Rats with subcutaneous human pancreatic adenocarcinoma xenografts were evaluated in vivo by dynamic positron emission tomography (PET) and ex vivo by measuring radioactivity of excised tissues and by digital autoradiography of tumor cryosections. RESULTS: Both tracers were capable of delineating all subcutaneous tumors from surrounding tissues by PET. The standardized uptake values of tumors by PET were 0.9 +/- 0.3 (mean +/- SD) for (68)Ga-chloride (n = 13) and 1.8 +/- 1.2 for FDG (n = 11). Ex vivo studies showed tumor-to-muscle ratio of 4.0 +/- 0.3 for (68)Ga-chloride (n = 4) and 7.9 +/- 3.2 for FDG (n = 4). CONCLUSIONS: (68)Ga-chloride delineated subcutaneously implanted pancreatic adenocarcinoma xenografts by PET, but the uptake was lower than FDG. Further studies to clarify the value of (68)Ga-chloride for PET imaging of tumors are warranted.
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Fluorodesoxiglucosa F18 , Galio , Trasplante de Neoplasias/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía de Emisión de Positrones , Animales , Autorradiografía , Línea Celular Tumoral , Galio/farmacocinética , Radioisótopos de Galio/farmacocinética , Humanos , Inmunohistoquímica , Neoplasias Pancreáticas/patología , Ratas , Distribución TisularRESUMEN
Carbon-11 choline has recently been introduced as a potential tracer for tumour imaging with positron emission tomography (PET). We evaluated the kinetics of the uptake of [(11)C]choline in prostate cancer and benign prostatic hyperplasia. We also evaluated the association between the uptake of [(11)C]choline and the histological grade of malignancy, Gleason score, volume of the prostate and prostate-specific antigen (PSA). Fourteen patients with histologically confirmed prostate cancer and five patients with benign prostatic hyperplasia were studied with [(11)C]choline PET. A mean dose of 430+/-31 MBq of [(11)C]choline was injected intravenously and a dynamic emission acquisition of prostate was performed for 30 min. The uptake of [(11)C]choline was measured as a standardised uptake value (SUV) and as a kinetic influx constant ( K(i)) obtained from graphical analysis. Both cancerous and hyperplastic prostate were well visualised with [(11)C]choline against low or moderate tracer accumulation in the bladder and rectal wall. The measured radioactivity in urine was invariably low. In the graphical analysis, linear plots were achieved. The mean K(i) of the untreated tumour was 0.205+/-0.089 min(-1) (range 0.128-0.351; n=7) and the mean SUV was 5.6+/-3.2 (range 1.9-15.5; n=15). K(i) values and SUVs correlated closely ( r=0.964, P=0.0005), whereas no correlation could be demonstrated between the tumour uptake of [(11)C]choline and the histological grade, Gleason score, volume of the prostate or PSA. The mean SUV and the mean K(i) of benign hyperplastic prostate were 3.5+/-1.0 (range 2.0-4.5; n=4) and 0.119+/-0.076 min(-1) (range 0.065-0.173; n=2). In conclusion, a high uptake of [(11)C]choline characterises not only carcinomatous but also hyperplastic prostatic tissue. Dynamic imaging of the uptake of [(11)C]choline in the prostate shows a good applicability of the graphical analysis model with an irreversible compartment. A close correlation between the K(i) values and semiquantitative SUVs of tumours supports the use of the simpler SUV in the clinical setting.
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Colina/farmacocinética , Interpretación de Imagen Asistida por Computador/métodos , Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Anciano , Anciano de 80 o más Años , Radioisótopos de Carbono/farmacocinética , Humanos , Cinética , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Próstata/diagnóstico por imagen , Próstata/metabolismo , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/sangre , Hiperplasia Prostática/clasificación , Hiperplasia Prostática/diagnóstico por imagen , Hiperplasia Prostática/metabolismo , Neoplasias de la Próstata/irrigación sanguínea , Neoplasias de la Próstata/clasificación , Radiofármacos/farmacocinética , Estadística como AsuntoRESUMEN
OBJECTIVE: To compare positron emission tomography (PET) and magnetic resonance imaging (MRI) in the evaluation of inflammatory proliferation of synovium. METHODS: Ten patients (mean +/- SD age 36 +/- 13 years) with inflammatory joint disease and with clinical signs of inflammation of the joint were studied. A new tracer for cellular proliferation, methyl-(11)C-choline ((11)C-choline), and a widely used tracer for the detection of inflammation and cancer, 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), were applied for PET imaging, and the results were compared with the findings from gadolinium diethylenetriaminepentaacetic acid-enhanced MR images. The uptake of (11)C-choline and (18)F-FDG in the inflamed synovium was measured and expressed as the standardized uptake value (SUV) and the kinetic influx constant (K(i)) obtained from graphic analysis, and these values were compared with quantitative values on MRI. Synovial volumes were measured on the coronal contrast-enhanced T1-weighted MR images using the standard software of the MR imager. RESULTS: All patients showed high accumulation of both (11)C-choline and (18)F-FDG at the site of arthritic changes, where quantification of the tracer uptake was performed. The SUV of (11)C-choline was 1.5 +/- 0.9 gm/ml (mean +/- SD; n = 10) and the SUV of (18)F-FDG was 1.9 +/- 0.9 gm/ml (n = 10) (P = 0.017). The K(i) of (11)C-choline (mean +/- SD 0.048 +/- 0.042 minute(-1)) was 8-fold higher than the K(i) of (18)F-FDG (0.006 +/- 0.003 minute(-1)) (P = 0.009). Both the uptake of (11)C-choline and the uptake of (18)F-FDG correlated highly with the volume of synovium; the highest correlation was observed with the K(i) of (11)C-choline (r = 0.954, P < 0.0001). CONCLUSION: In the use of PET scans,(11)C-choline can be regarded as a promising tracer for quantitative imaging of proliferative arthritis changes. Nevertheless, subsequent prospective studies with larger numbers of patients are necessary to further characterize the relationship between the findings on PET imaging and the clinical and functional measures of inflammation.
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Artritis/diagnóstico , Imagen por Resonancia Magnética/métodos , Sinovitis/diagnóstico , Tomografía Computarizada de Emisión/métodos , Adulto , Articulación del Tobillo/metabolismo , Articulación del Tobillo/patología , Artritis/metabolismo , Colina/farmacocinética , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Gadolinio DTPA , Humanos , Articulación de la Rodilla/metabolismo , Articulación de la Rodilla/patología , Masculino , Persona de Mediana Edad , Radiofármacos/farmacocinética , Sinovitis/metabolismoRESUMEN
The [(18)F]fluoromethyl analog of (+)-McN5652 ([(18)F]FMe-McN) for imaging serotonin transporter (SERT) with positron emission tomography (PET) has recently been synthesized. We describe here the biological evaluation of [(18)F]FMe-McN in rats. Biodistribution studies of [(18)F]FMe-McN in rat brain ex vivo after an intravenous injection showed a high accumulation of radioactivity in the regions rich in SERT, such as raphe nuclei, hypothalamus, thalamus, substantia nigra, locus coeruleus, and amygdala. Region-to-cerebellum ratios reached a maximum value of 9 in raphe nuclei within 3.5 h after administration. The specificity and selectivity of [(18)F]FMe-McN binding to SERT was studied by preinjecting blocking doses of serotonin, norepinephrine, and dopamine transporter inhibitors. Fluoxetine, a specific inhibitor for SERT, decreased the specific binding of [(18)F]FMe-McN in raphe nuclei by 91 +/- 4%; in other regions rich in SERT, similar results were obtained. GBR12909 and nisoxetine, selective inhibitors for dopamine transporter (DAT) and norepinephrine transporter (NET), respectively, showed no significant effects on the uptake of [(18)F]FMe-McN. Our studies show that [(18)F]FMe-McN has a clear potential as a tracer for studies with PET of SERT function in humans.
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Encéfalo/metabolismo , Proteínas Portadoras/metabolismo , Fluoxetina/análogos & derivados , Isoquinolinas , Glicoproteínas de Membrana/metabolismo , Proteínas del Tejido Nervioso , Trazadores Radiactivos , Antagonistas de la Serotonina , Tomografía Computarizada de Emisión/métodos , Animales , Autorradiografía , Proteínas Portadoras/antagonistas & inhibidores , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Inhibidores de Captación de Dopamina/farmacología , Femenino , Radioisótopos de Flúor , Fluoxetina/farmacología , Masculino , Glicoproteínas de Membrana/antagonistas & inhibidores , Moduladores del Transporte de Membrana , Proteínas de Transporte de Membrana/antagonistas & inhibidores , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática , Piperazinas/farmacología , Ratas , Ratas Sprague-Dawley , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Simportadores/antagonistas & inhibidoresRESUMEN
BACKGROUND: Exercise intolerance is a hallmark symptom in patients with heart failure; however, myocardial factors contributing to the limited exercise capacity are not fully characterized. METHODS: Twenty patients with stable heart failure resulting from idiopathic dilated cardiomyopathy (DCM) and 13 controls were studied. Myocardial perfusion, biventricular oxidative metabolism, and insulin-stimulated glucose uptake were measured using positron emission tomography and [(15)O]H(2)O, [(11)C]acetate, and [(18)F]FDG. RESULTS: Hyperemic perfusion and perfusion reserve were significantly lower in the DCM patients compared with the healthy subjects. There was no difference in left ventricular oxidative metabolism between the 2 groups; however, the patients had a 19% higher right ventricular oxidative metabolism (P=.005). Consequently, the ratio of right to left ventricular oxidative metabolism was also higher (31%) in the patients. There was a strong inverse association between decreased exercise capacity and the ratio of right to left ventricular oxidative metabolism (r=-.68, P<.01) and a positive association with myocardial perfusion reserve (r=.62, P<.01) in the patient group. These 2 parameters along with resting left ventricular work explained 57% of the variability in peak exercise capacity. CONCLUSIONS: Impaired perfusion reserve and an exaggerated imbalance in right to left ventricular oxidative metabolism appear to significantly contribute to the impaired exercise capacity in these DCM patients.