RESUMEN
OBJECTIVES: The relation of myocardial blood flow and indium-111 (111In) antimyosin antibody uptake was studied by inducing myocardial infarction in 18 dogs, 8 with closed chest left anterior descending artery balloon occlusion for 3 h followed by reperfusion (group A) and 10 dogs with open chest left anterior descending artery ligation (without reperfusion, group B). BACKGROUND: The relation of antimyosin uptake to myocardial injury has been documented. However, its relation to tracer delivery by myocardial blood flow has not been studied and has been assumed to be independent. METHODS: Indium-111 antimyosin antibody, 2 mCi, was injected 20 min after reperfusion and 3 h after coronary artery ligation in groups A and B, respectively. Regional blood flows were determined by radiolabeled microspheres during occlusion and 24 h later in both groups. On day 2, dogs were killed after risk zone delineation with gentian violet. The heart was excised and stained with triphenyltetrazolium chloride solution and graded for increasing severity of tissue injury based on extent of staining. Microsphere activity and 111In antimyosin activity were measured in control tissue (grade 1), noninfarct tissue at risk (grade 2), mixed tissue (grade 3), infarct tissue (grade 4) and hemorrhagic infarct tissue (grade 5, present only in group A dogs). Count activity was normalized to that of the mean value in control tissue (grade 1) and expressed as a ratio of activity. RESULTS: Indium-111 antimyosin activity was high in triphenyltetrazolium chloride grade 4 tissue in both groups but was attenuated in grade 4 tissue in group B dogs (10.6 +/- 5.1 vs. 5.0 +/- 4.5; p < 0.05 group A vs. group B), which had lower blood flow on day 2 (0.51 +/- 0.36 vs. 0.23 vs. 0.22; p < 0.01). Normalizing 111In antimyosin activity for blood flow on day 2 resulted in equivalent 111In antimyosin uptake for infarct tissue (32.6 +/- 21.6 vs. 36.6 +/- 29.8 for group A vs. group B; p = NS). CONCLUSIONS: Thus, 111In antimyosin uptake is a specific marker of necrotic tissue with a high signal ratio in reperfused tissue. However, its uptake is dependent on residual blood flow in the infarct territory. Indium-111 antimyosin could potentially serve as a suitable tracer for infarct sizing if myocardial blood flow in the same region were factored simultaneously.
Asunto(s)
Anticuerpos Monoclonales , Circulación Coronaria , Radioisótopos de Indio , Infarto del Miocardio/diagnóstico por imagen , Miosinas/inmunología , Animales , Modelos Animales de Enfermedad , Perros , Evaluación Preclínica de Medicamentos , Corazón/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Reperfusión Miocárdica , Miocardio/patología , Cintigrafía , Coloración y Etiquetado , Sales de TetrazolioRESUMEN
We used positron emission tomography to investigate local cerebral metabolic rates for glucose (LCMRG1c) in patients with obsessive-compulsive disorder before and after treatment with either fluoxetine hydrochloride or behavior therapy. After treatment, LCMRG1c in the head of the right caudate nucleus, divided by that in the ipsilateral hemisphere (Cd/hem), was decreased significantly compared with pretreatment values in responders to both drug and behavior therapy. These decreases in responders were also significantly greater than right Cd/hem changes in nonresponders and normal controls, in both of whom values did not change from baseline. Percentage change in obsessive-compulsive disorder symptom ratings correlated significantly with the percent of right Cd/hem change with drug therapy and there was a trend to significance for this same correlation with behavior therapy. By lumping all responders to either treatment, right orbital cortex/hem was significantly correlated with ipsilateral Cd/hem and thalamus/hem before treatment but not after, and the differences before and after treatment were significant. A similar pattern was noted in the left hemisphere. A brain circuit involving these brain regions may mediate obsessive-compulsive disorder symptoms.
Asunto(s)
Terapia Conductista , Núcleo Caudado/metabolismo , Fluoxetina/uso terapéutico , Glucosa/metabolismo , Trastorno Obsesivo Compulsivo/metabolismo , Adulto , Corteza Cerebral/metabolismo , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Lateralidad Funcional , Giro del Cíngulo/metabolismo , Humanos , Masculino , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trastorno Obsesivo Compulsivo/terapia , Tálamo/metabolismo , Tomografía Computarizada de EmisiónRESUMEN
We examined chorea-free subjects at risk for Huntington's disease (n = 52) for lifetime psychiatric diagnoses, present mood, genetic marker status, and caudate glucose metabolic rates with positron emission tomography. Based on previous work, a caudate-ipsilateral hemisphere ratio less than 1.15 was defined as abnormal and predictive of Huntington's disease. None of three methods used to segregate subjects into groups more and less likely to develop Huntington's disease gave significant group rate differences for any formal psychiatric diagnoses. On present mood testing, however, subjective "anger/hostility" was significantly higher in those likely, compared with those less likely, to develop Huntington's disease, as determined by all three methods.
Asunto(s)
Enfermedad de Huntington/genética , Trastornos Mentales/epidemiología , Adulto , Anciano , Núcleo Caudado/metabolismo , Femenino , Marcadores Genéticos , Glucosa/metabolismo , Humanos , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/metabolismo , Funciones de Verosimilitud , Masculino , Trastornos Mentales/diagnóstico , Persona de Mediana Edad , Modelos Genéticos , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Tomografía Computarizada de EmisiónRESUMEN
Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and sex-matched, right-handed patients with unipolar depression (n = 10), bipolar depression (n = 10), obsessive-compulsive disorder (OCD) with secondary depression (n = 10), OCD without major depression (n = 14), and normal controls (n = 12). Depressed patients were matched for depression on the Hamilton Depression Rating Scale, and subjects with OCD without depression and OCD with depression had similar levels of OCD without depression and OCD with depression had similar levels of OCD pathology. We also studied six non-sex-matched patients with mania. Mean (+/- SD) glucose metabolic rates for the left dorsal anterolateral prefrontal cortex, divided by the rate for the ipsilateral hemisphere as a whole (ALPFC/hem), were similar in the primary depressions (unipolar depression = 1.05 +/- 0.05; bipolar depression = 1.04 +/- 0.05), and were significantly lower than those in normal controls (1.12 +/- 0.06) or OCD without depression (1.15 +/- 0.05). Results for the right hemisphere were similar. Values in subjects with OCD with depression (1.10 +/- 0.05) were also significantly lower than in subjects with OCD without depression, and values in subjects with bipolar depression were lower than those in manic subjects (1.12 +/- 0.03) on this measure in the left hemisphere, although results were not significant in the right hemisphere. There was a significant correlation between the HAM-D score and the left ALPFC/hem. With medication for depression (n = 12), the left ALPFC/hem increased significantly and the percentage change in the Hamilton scale score correlated with the percentage change in the left ALPFC/hem.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Trastorno Depresivo/metabolismo , Lóbulo Frontal/metabolismo , Glucosa/metabolismo , Adulto , Anciano , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/metabolismo , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Trastorno Depresivo/diagnóstico , Diagnóstico Diferencial , Femenino , Fluorodesoxiglucosa F18 , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/metabolismo , Escalas de Valoración Psiquiátrica , Tomografía Computarizada de EmisiónRESUMEN
Sex-related differences have been reported for some brain neuroanatomical structures and several measures of brain function. We studied the cerebral glucose metabolic rates of normal men (n = 7) and women (n = 7) with positron emission tomography and the fluorodeoxyglucose method. Women were studied between days 5 and 15 of the menstrual cycle. Women had whole brain glucose metabolic rates that were 19% higher than those of men. All neuroanatomical structures surveyed showed significant female greater than male rates, with no particular regions being outstanding. The higher cerebral glucose metabolic rates we observed in women may have been related to the effects of the high estrogen levels that can obtain in the phase of the menstrual cycle during which we tested our female subjects.
Asunto(s)
Glucemia/metabolismo , Encéfalo/metabolismo , Adulto , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Humanos , Cinética , Masculino , Valores de Referencia , Factores Sexuales , Tomografía Computarizada de EmisiónRESUMEN
The isolated arterially perfused rabbit interventricular septum was used to measure myocardial metabolic rate for glucose (MMRGlc) and rate constants and lumped constant (LC) for the glucose analogue [18F]fluorodeoxyglucose (FDG) using a tracer kinetic model. FDG was delivered by constant infusion during coincidence counting of tissue 18F radioactivity. The MMRGlc was measured by the Fick method. Control septa were paced at 72 beats/min and perfused at 1.5 ml/min with oxygenated perfusate containing 5.6 mM glucose and 5 mU/ml insulin. The following conditions were tested: 3.0 and 4.5 ml/min; insulin increased to 25 mU/ml; insulin omitted; 2.8 mM and 11.2 mM glucose; 144 beats/min and 96 paired stimuli/min; and anoxia. Under all conditions studied the phosphorylation (hexokinase) reaction was rate limiting relative to transport. Compared with control conditions, the phosphorylation rate constant was significantly increased with 2.8 mM glucose as well as in anoxia. With 4.5 ml/min and 11.2 mM glucose, conditions that should increase glucose flux into tissue without increasing demand, the phosphorylation rate constant decreased significantly. With 11.2 mM glucose, 96 paired stimuli/min, and anoxia without insulin, a significant increase in the hydrolysis rate of FDG 6-phosphate was observed and suggests that hydrolysis is also an important mechanism for regulating the MMRGlc. Increased transport rate constants were observed with increased flow rates, 96 paired stimuli/min, and anoxia at 96 beats/min. The LC was not significantly different from control in 11 of 14 conditions studied. Therefore, under most conditions, an average LC can be used to calculate MMRGlc estimates.
Asunto(s)
Desoxiazúcares/metabolismo , Desoxiglucosa/metabolismo , Glucosa/metabolismo , Miocardio/metabolismo , Animales , Velocidad del Flujo Sanguíneo , Desoxiglucosa/análogos & derivados , Fluorodesoxiglucosa F18 , Glucofosfatos/metabolismo , Hipoxia/metabolismo , Insulina/farmacología , Cinética , Modelos Teóricos , ConejosRESUMEN
We studied 14 patients with obsessive-compulsive disorder (OCD) by positron emission tomography and the fluorodeoxyglucose method, looking for abnormalities in local cerebral metabolic rates for glucose in brain structures that have been hypothesized to function abnormally in OCD. These patients were compared with 14 normal controls and 14 patients with unipolar depression. The patients with unipolar depression and OCD did not differ in levels of anxiety, tension, or depression. In OCD, metabolic rates were significantly increased in the left orbital gyrus and bilaterally in the caudate nuclei. This was apparent on all statistical comparisons with both controls and unipolar depression. The right orbital gyrus showed at least a trend to an increased metabolic rate in all comparisons. The metabolic rate in the left orbital gyrus, relative to that in the ipsilateral hemisphere (orbital gyrus/hemisphere ratio), was significantly elevated compared to controls and subjects with unipolar depression, and stayed high even with successful drug treatment. Though it was in the normal range in the morbid state, with improvement in OCD symptoms after drug treatment, the caudate/hemisphere metabolic ratio increased uniformly and significantly bilaterally. This ratio did not increase in patients who did not respond to treatment. Thus, OCD showed cerebral glucose metabolic patterns that differed from controls in both the symptomatic and recovered states.
Asunto(s)
Encéfalo/metabolismo , Trastorno Depresivo/metabolismo , Glucosa/metabolismo , Trastorno Obsesivo Compulsivo/metabolismo , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/efectos de los fármacos , Núcleo Caudado/metabolismo , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/tratamiento farmacológico , Diagnóstico Diferencial , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Tomografía Computarizada de Emisión , Trazodona/farmacología , Trazodona/uso terapéuticoRESUMEN
Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is difficult to treat. The effects of trazodone hydrochloride treatment were studied, both with and without the addition of a monoamine oxidase inhibitor, in OCD patients. Changes in symptoms correlated with changes in local cerebral metabolic rates for glucose (LCMRGlc), as measured by positron emission tomography and the 18F-fluorodeoxyglucose method. All patients whose OCD responded favorably to drug treatment showed a relative increase in glucose metabolism in the heads of the caudate nuclei compared with the metabolic rate in the ipsilateral hemisphere as a whole (ratio LCMRGlc caudate/LCMRGlc hemisphere). Patients who did not respond to treatment did not show an increase in this ratio, and the difference between responders and nonresponders was significant (p less than 0.03). Changes in the ratio LCMRGlc caudate/LCMRGlc hemisphere correlated with changes on OCD and depression rating scales.
Asunto(s)
Glucemia/metabolismo , Núcleo Caudado/efectos de los fármacos , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Trazodona/uso terapéutico , Adulto , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenelzina/uso terapéutico , Pruebas Psicológicas , Tomografía Computarizada de EmisiónRESUMEN
Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N = 11), bipolar depression (N = 5), mania (N = 5), bipolar mixed states (N = 3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression.
Asunto(s)
Encéfalo/metabolismo , Trastorno Depresivo/metabolismo , Glucosa/metabolismo , Adulto , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/metabolismo , Trastorno Bipolar/psicología , Encéfalo/diagnóstico por imagen , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/metabolismo , Desoxiglucosa/análogos & derivados , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Diagnóstico Diferencial , Femenino , Flúor , Fluorodesoxiglucosa F18 , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Radioisótopos , Tomografía Computarizada de EmisiónRESUMEN
The isolated arterially perfused rabbit interventricular septum was used to determine the feasibility of using the glucose analogue 18F-2-deoxy-2-fluoro-d-glucose (DG) with a tracer kinetic model to estimate the rate of exogenous glucose utilization. FDG was delivered to the septum by constant infusion, and tissue 18F radioactivity was measured as a function of time by external coincidence counting. The following four conditions were studied: flow rates of 0.5, 1.0, and 1.5 ml/min with a heart rate of 72 beats/min and flow at 1.5 ml/min with 96 beats/min. The rate constants for FDG forward and reverse transport between the vascular and extravascular compartments (k*1, k*2, respectively), phosphorylation of FDG (k*3), and dephosphorylation of FDG-6-phosphate (FDG-6-P) (k*4) were determined from the tissue curves using a tracer kinetic model. The lumped constant (LC) of the deoxyglucose model calculated using Fick-derived myocardial metabolic rates of glucose (MMRGlc), was 0.60 +/- 0.10 and was stable over the range of conditions studied. Average k*'s and LC were used to calculate MMRGlc's employing the model and were not significantly (P greater than 0.05) different from those determined by the Fick method. Tissue analyses using high-pressure liquid chromatography documented that tissue 18F radioactivity wa due to FDG and FDG-6-P, and their relative fractions agreed well with the values predicted from the tracer kinetic model. Only FDG was detected in the effluent. These studies also indicate the presence of a myocardial enzyme that can hydrolyze FDG-6-P to FDG. Thus our results support the use of the FDG method with positron-computed tomography for the in vivo determination of the myocardial rate of exogenous glucose utilization.
Asunto(s)
Desoxiazúcares/metabolismo , Desoxiglucosa/metabolismo , Glucosa/metabolismo , Miocardio/metabolismo , Animales , Desoxiglucosa/análogos & derivados , Fluorodesoxiglucosa F18 , Técnicas In Vitro , Cinética , Matemática , Modelos Biológicos , Perfusión , ConejosRESUMEN
The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to cardiac studies with positron computed tomography (PCT) and fluorodeoxyglucose (FDG). Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by arterial and venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. Error propagation, primarily from corrections applied to remove spillover of activity from the myocardial blood pool to tissue and from partial-volume effects in the PCT images, limited accuracy in the estimation of the individual rate constants for transport, phosphorylation, and dephosphorylation. However, a constant representing the combination of transport and phosphorylation was accurately determined and yielded measured values of the myocardial metabolic rate for glucose (MMRGlc) that were in good agreement with direct determinations using the Fick method over a wide range of glucose metabolic rates (from 1.7 to 21.1 mg/min-100 g). The lumped constant (0.67 +/- 0.10) was also found accurate and stable over this range of metabolism. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was five times the control value, or when metabolism was reduced to 10% of normal and MBF increased to five times normal. Improvements of PCT resolution are required to improve the accuracy of the estimates of the rate constant and the MMRGlc.
Asunto(s)
Desoxiazúcares/análisis , Desoxiazúcares/metabolismo , Desoxiglucosa/análisis , Desoxiglucosa/metabolismo , Miocardio/análisis , Tomografía Computarizada de Emisión , Animales , Unión Competitiva , Transporte Biológico , Circulación Coronaria , Desoxiglucosa/análogos & derivados , Perros , Fluorodesoxiglucosa F18 , Cinética , Matemática , Modelos Biológicos , Miocardio/metabolismo , Distribución TisularRESUMEN
To determine the variables that might affect interpretability of myocardial perfusion images in patients with acute myocardial infarctions, images obtained following intravenous administration of potassium-43 or cesium-129 were evaluated in 68 patients with nonacute coronary or noncoronary heart diseases, who were undergoing cardiac catheterization. Severe coronary arterial disease usually produces no distinctive perfusion defects in the resting state. Remote infarcts likewise tend to remain undetectable unless accompanied by wall-motion disturbances that can be detected by ventriculography. Left ventricular hypertrophy or cardiac dilatation can produce perfusion patterns indistinguishable from the ischemic defects of infarction. Right ventricular hypertrophy can cause image alterations that mimic infarcts in the left ventricle. In patients with acute myocardial infarction, sequential imaging studies with perfusion indicators should be of value in determining the effects of various therapeutic maneuvers on regional myocardial perfusion, but variations caused by conditions other than acute vascular occlusion limit the usefulness of perfusion imaging for diagnosing acute infarction. In suspected acute infarction, perfusion imaging will be used most effectively in conjunction with other imaging or nonimaging procedures that show the presence of damaged or necrotic myocardium. The information derived from this study should be generally applicable to the interpretation of imaging results obtained with the newer indicators of myocardial perfusion now in use or under development.