Central nervous system norepinephrine turnover in essential hypertension.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
V Kalff
Publications and source records attributed to V Kalff.
Is planar thallium-201/fluorine-18 fluorodeoxyglucose imaging a reasonable clinical alternative to positron emission tomographic myocardial viability scanning?
This comparative study was performed to determine whether a conventional planar gamma camera optimised for 511-keV imaging can reliably assess myocardial viability using the fluorine-18 fluorodeoxyglucose (FDG) metabolic tracer previously developed for positron emission tomography (PET). Twenty-seven patients with severe ischaemic cardiomyopathy (mean left ventricular ejection fraction: 20% +/- 9%) having clinically indicated nitrogen-13 ammonia/FDG PET myocardial viability studies consented to resting, four-view, planar myocardial thallium-201 perfusion and FDG metabolism imaging. The resultant PET and planar perfusion/metabolism images (PPI) were independently assessed for FDG defect size and perfusion/metabolism mismatch, using a four-point scale, in each of four vascular regions: apex, circumflex, left anterior and posterior descending coronary artery territories. Of 108 regions, 106 were evaluable (two not assessed by PET). There was complete agreement in 70% of coronary vascular territories, giving an unweighted kappa score of 0.56. Moreover, in 94% of segments agreement was within one grade. Interestingly, six of the seven differences of more than one grade occurred in the circumflex coronary territory, which was also the only region for which planar positron imaging underestimated FDG defect size. Three of four moderate areas of perfusion/metabolism mismatch seen with PET were also seen on PPI. PPI showed three small regions of mismatch not seen on PET, whilst the reverse occurred with one other small region of mismatch. Thus, for this PET protocol, PPI provides very similar information on the extent of regional FDG uptake and occurrence of mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Central nervous system noradrenergic and dopaminergic turnover in response to acute neuroleptic challenge.
The objective of this study was to obtain direct neurochemical measures of the central nervous system's response to a typical neuroleptic, haloperidol, in human subjects. Nine healthy volunteers participated in this study. Central nervous system neuronal activity was assessed by measuring the plasma concentration and overflow from the brain of dopamine, norepinephrine, and their lipophilic and acidic metabolites after acute intravenous administration of haloperidol. By combining bilateral internal jugular vein blood sampling with cerebral blood flow scans we were able to differentiate between cortical and subcortical responses to haloperidol. The central nervous system response to haloperidol administration displayed a degree of regional specificity. Dopamine release, estimated from the overflow of homovanillic and dihydroxyphenylacetic acids, was reduced in cortical but not subcortical brain regions. Norepinephrine turnover was increased in cortical and subcortical brain regions. The overflow of homovanillic acid from the brain into the internal jugular veins was not related quantitatively to the arterial plasma concentrations of the catecholamines examined, homovanillic and dihydroxyphenylacetic acids or prolactin. Measurements of catecholamines and their metabolites in arterial plasma gave little indication as to monoaminergic neuronal activity in the brain.
Adolescent↗
Monoaminergic neuronal activity in subcortical brain regions in essential hypertension.
In this study we aimed to elucidate the role of central noradrenergic, dopaminergic, adrenergic and serotonergic neuronal systems in the development of essential hypertension. Fifteen untreated essential hypertensive subjects (aged 44 +/- 3 years) and 32 healthy volunteers (aged 38 +/- 3 years) participated in this study. By combining direct blood sampling techniques with cerebral blood flow scans we were able to differentiate between cortical and subcortical venous drainage of the brain. Veno-arterial MHPG, HVA and 5-HIAA plasma concentration gradients combined with internal jugular vein plasma flows were used, according to the Fick Principle, to derive metabolite spillovers which in turn were used as indicators of central noradrenergic, dopaminergic and serotonergic neuronal activity, respectively. These amine systems, in both the brainstem and forebrain, have been implicated in the regulation of sympathetic outflow and blood pressure. Total body noradrenaline spillover to plasma was concurrently measured to assess the relationship between central monoamine turnover and sympathetic activity. Compared to their healthy counterparts the hypertensive subjects had an elevated release of MHPG from subcortical brain regions (1.4 +/- 0.3 v 0.5 +/- 0.2 nmol/min, p < 0.05). An inverse relationship between blood pressure and subcortical HVA overflow existed, with the HVA overflow being significantly lower in the hypertensives (0.5 +/- 0.2 v 2.1 +/- 0.5 nmol/min, p < 0.05). Subcortical 5-HUAA overflow did not differ between the two groups, and adrenaline spillover from the brain was not detected in either group. Subcortical MHPG overflow was significantly correlated with total body NA spillover to plasma (p < 0.05). These results indicate that reciprocal aberrations in subcortical noradrenaline and dopamine turnover exist in essential hypertension. Although the physiological significance of this remains to be unequivocally elucidated we postulate that elevated subcortical noradrenergic activity, presumably in the forebrain where noradrenergic neurons are pressor, may cause sympathoexcitation and play a role in the development of essential hypertension.
3,4-Dihydroxyphenylacetic Acid↗
Assessment of myocardial oxidative metabolism in aortic valve disease using positron emission tomography with C-11 acetate.
C-11 acetate has recently been introduced as a tracer of myocardial oxidative metabolism with the use of positron emission tomography. To evaluate this approach in the pressure- or volume-loaded heart, C-11 acetate clearance rate constants were determined in 22 patients with chronic aortic valve disease and in nine normal subjects. Global myocardial C-11 clearance was significantly higher in patients with predominant aortic stenosis (n = 11) or aortic regurgitation (n = 11) than in normal subjects (0.069 +/- 0.017 min-1 and 0.072 +/- 0.010 min-1 compared with 0.050 +/- 0.004 min-1, p less than 0.05) and correlated significantly with the rate-pressure product corrected for mean aortic valve gradient (r = 0.73, p = 0.0001) for all studies. However, analysis of patient subgroups demonstrated that this correlation held only for aortic stenosis (r = 0.79, p less than 0.005 for gradient-corrected rate-pressure product). Additionally, C-11 clearance was strongly correlated with the product of heart rate and mean wall stress in patients with aortic stenosis (r = 0.89, p less than 0.005) but not in patients with aortic regurgitation. Normalization of C-11 acetate clearance rate constants for gradient-corrected rate-pressure product were significantly lower in patients with loaded ventricles, particularly in the presence of a low ejection fraction, compared to normal subjects. Possible mechanisms include myocardial adaptation through hypertrophy or depressed contractility, which would both tend to reduce oxygen consumption under any given load. Serial comparison of C-11 acetate kinetics and noninvasive indexes of oxygen demand may provide assessment of disease progression in pathologic ventricular loading.
Acetates↗
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.
Adult↗
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.
Animals↗
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.
Acetates↗
Direct determination of homovanillic acid release from the human brain, an indicator of central dopaminergic activity.
The plasma concentration of the dopamine (DA) metabolite, homovanillic acid (HVA), is used as an indicator of central nervous system dopaminergic activity. Using percutaneously inserted catheters we were able to obtain blood samples simultaneously from the right and left internal jugular veins. Veno-arterial HVA plasma concentration differences combined with adjusted organ plasma flows were used, according to the Fick Principle, to determine the HVA overflow from the brain. The HVA overflow from the liver was also measured. HVA overflow from the brain represented 12% of the total body HVA production. A similar amount was released from the liver, illustrating the limited validity of peripheral plasma HVA measurements as an indicator of central dopaminergic activity. HVA release from the human brain displayed a degree of asymmetry, the overflow into the left internal jugular vein being 36% greater than that into the right. Cerebral venous blood flow scans indicated that cortical cerebral regions drained preferentially into the right internal jugular; by inference the higher HVA overflow on the left originated from dopamine-rich subcortical brain areas. Since HVA in plasma may arise from the metabolism of DA existing either as a neurotransmitter or a norepinephrine (NE) precursor we measured the internal jugular vein plasma concentrations of NE, and its metabolite dihydroxyphenylglycol (DHPG), to determine whether they displayed a similar pattern of release to HVA. The overflow of both NE and DHPG into the right internal jugular vein was approximately double that on the left. Since the overflow of HVA did not parallel that of NE and DHPG it may be inferred that the origin of much of the subcortically produced HVA is from dopaminergic neurons and not from the metabolism of precursor DA in noradrenergic neurones or cerebrovascular sympathetic nerves.
Adolescent↗
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.
Acetates↗
Normalization of left ventricular ejection fraction following resection of pheochromocytoma in a patient with dilated cardiomyopathy.
Catecholamine-induced cardiomyopathy associated with pheochromocytoma is a well-recognized but rare entity. Both hypertrophic and dilated variants have been described. We report a case of dilated cardiomyopathy associated with a benign pheochromocytoma that showed complete normalization of left ventricular systolic function following removal of the tumor. Serum noradrenaline and dopamine were significantly elevated without elevation in serum adrenaline levels. This may be the first report in which radionuclide ventriculography was used to document the time course of normalization in LVEF following removal of a pheochromocytoma.
Adolescent↗
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.
Blood Pressure↗
Hepatobiliary imaging.
Recent publications continue to refine the technique and interpretation of hepatobiliary scanning. Studies related to the evaluation of suspected acute cholecystitis have shown that morphine-augmented hepatobiliary imaging may not overcome the problem of false-positive study results in severely ill patients and the criterion for a normal study should be gallbladder visualization within 30 rather than 60 minutes. In patients with suspected acute cholecystitis, nonvisualized extrahepatic activity despite good hepatic uptake is highly predictive of acute cholecystitis, usually with biliary obstruction. The limitations of cholecystokinin-hepatobiliary imaging studies in patients with abdominal pain syndromes were defined and its use in evaluating common bile duct dynamics, and duodenogastric reflux was explored. Unusual findings and less-common uses of hepatobiliary scanning were reported, including assessment of conjoined twins, liver transplantation, primary biliary cirrhosis, gallbladder perforation, and persistent splenic visualization.
Biliary Tract↗
111In-oxine labelled leukocyte scintigraphy in the detection and localization of active inflammation and sepsis.
We report an analysis of the results obtained in our first 100 studies with indium-111-oxine labelled leukocyte scintigraphy, a diagnostic technique which has recently become available for clinical evaluation within Australia. We used this technique to assess patients with suspected sepsis or inflammation after other commonly used investigations had failed to confirm a diagnosis. Four patient subgroups were evaluated: fever of unknown origin; suspected abdominal or postoperative sepsis; suspected active inflammatory bowel disease; and suspected sepsis or inflammation of bones or joints. The course of all patients was followed for at least three months to establish the accuracy of the technique. The leukocyte labelling procedure took 90 min and imaging was carried out typically 3-6, 24 and occasionally 48 h after reinjection of the labelled autologous leukocytes. In one patient labelling of leukocytes was unsuccessful. In the remaining 99 studies the overall sensitivity of leukocyte scintigraphy was 88% (36 of 41 patients with a proved inflammatory or infective disease focus had positive scan findings); and the specificity was 95% (55 of 58 cases with no proved disease focus had normal scan findings). This series supports the use of this method as the imaging procedure of choice in nuclear medicine for the evaluation of suspected acute sepsis (symptoms less than four weeks' duration), of inflammatory bowel disease and of suspected infections involving appendicular bones which contain no active bone marrow. It is also a useful secondary scintigraphic procedure, after gallium-67-citrate scintigraphy, in patients with suspected infective disorders of more than four weeks' duration.
Abdomen↗
Association between false negative hepatobiliary scans and initial gallbladder visualization after 30 min.
We have reviewed the experience of our institution and the literature concerning the use of hepatobiliary scintigraphy for the diagnosis of acute cholecystitis. The aim of this study was to assess whether the hepatobiliary scintigraphic finding of initial gallbladder visualization within 30 min is a more reliable criterion for excluding acute cholecystitis than gallbladder visualization within 1 h after tracer injection. In our institution's consecutive series, 113 of 211 hepatobiliary studies had gallbladder visualization within 1 h. Gallbladder visualization time in this group had a log normal distribution, with gallbladder visualization occurring within 30 min in 107 of 113 (95%). Gallbladder visualization occurred between 31 and 60 min in only 6 (5%); nevertheless, our one false negative study came from this small subgroup of patient studies (P = 0.05). Review of the literature (1645 patients with iminodiacetic acid [99mTc-IDA] derivative studies) revealed 6 further timed false negative results with gallbladder visualization within 1 h. Of these studies, in 4 (67%) the gallbladder was visualized between 31 and 60 min and in only 2 before 30 min. One of these latter 2 patients had a rare anatomy. Analysis of the pooled institutional and literature data gave an estimated false negative rate of 21% if the gallbladder was visualized between 31 and 60 min. This was significantly higher (P less than 0.001) than the 0.5% false negative rate when the gallbladder was seen prior to 30 min, but similar to the false negative rate of 16% reported by Weissmann et al. for studies with initial visualization after 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography.
The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial [11C]hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, [11C]hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart.
Adult↗
The radionuclide assessment of a system for slow intrathecal infusion of drugs.
The authors describe a new radionuclide method for assessing the functional integrity of slow intrathecal infusion devices. Approximately 11 mCi (400 MBq) of Tc-99m DTPA is injected into the pump chamber. Early and delayed imaging of the pump, tubing, and spinal cerebrospinal fluid space is performed on a digital large-field-of-view gamma camera. The digitally displayed images are then reviewed by adjustment of the grey scale window. Four patients have had eight studies and in each case the result has been confirmed by surgical exploration or by clinical response to change in therapy.
Aged↗
Longitudinal study of ventricular function after the Mustard operation for transposition of the great arteries: a long term follow up.
An earlier study of 25 patients who were investigated by radionuclide angiography after a Mustard procedure showed that they had had evidence of right and left ventricular dysfunction at rest and with exercise. Twenty one (mean age 17.0 years (range 13.7-20.6) 11 female patients) of the original 25 patients were followed up a mean of 4.3 years later (mean 14.6 years (range 12.5-16.0) after the procedure). The group means for resting right and left ventricular ejection fraction and exercise response were not significantly different from those reported five years before. Individual changes in values were within the normal variation seen in serial studies. This long term longitudinal follow up of patients after the Mustard operation showed that although some patients still had right and left ventricular dysfunction, resting ventricular function and exercise response remained stable over a five year period. This preservation of cardiac function may contribute to the long term survival of patients after the Mustard procedure.
Adolescent↗