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H Valette

Publications and source records attributed to H Valette.

At least 37 records · Page 2Linked to original sources
PubMed1995

In vivo metabolites of N omega-nitro-L-arginine methyl ester: methanol and N omega-nitro-L-arginine.

N omega-nitro-L-arginine methyl ester (L-NAME) is commonly used as a selective inhibitor for in vivo studies of brain nitric oxide (NO) synthase. We aimed to study the fate of N omega-nitro-L-arginine [11C]methyl ester ([11C]L-NAME) using positron emission tomography in monkey and high performance liquid chromatography methods in dogs and rats. We found that [11C]L-NAME was rapidly (t1/2 = 2 min) metabolized into N omega-nitro-L-arginine (L-NA) and [11C]methanol which both had a slow rate of elimination. Although, in vivo, L-NAME administration leads to long-lasting NO synthase inhibition by L-NA, methanol which is a potent neurotoxin in primate may produce detrimental effects unrelated to NO synthase inhibition.

Animals↗
PubMed1995

[Congenital pseudarthrosis of the clavicle and thoracic outlet syndrome. Report of a case and review of the literature].

The association pseudarthrosis of the clavicle and the thoracic outlet syndrome is rare. The author describe a case in a 64 years old man, found before embolic complications. Shoulder X-ray and artériography démonstrate the lesion. The etiopathogenic hypothesis are called up. In case of complication, the surgical treatment is made of osteo synthesis or partial or total resection of the clavicle, associated to a vascular repair in case of need. At long term the result is excellent.

Clavicle↗
PubMed1995

Canine myocardial beta-adrenergic, muscarinic receptor densities after denervation: a PET study.

UNLABELLED: In an effort to better understand cardiac neurotransmission, PET was serially used in dogs to assess changes in ventricular muscarinic (MR) and beta-adrenergic receptor (beta-AR) densities following chemical or surgical denervation. METHODS: Beta-adrenergic and MR receptor concentrations were studied in beagle dogs nine days after chemical sympathectomy (using the neurotoxin 6-hydroxydopamine) or 3-7 wk and 23-28 wk after surgical intrapericardial denervation. RESULTS: In control dogs (n = 13), global beta-AR and MR concentrations were 32 +/- 4 and 62.2 +/- 10.4 pmole/ml tissue, respectively. Nine days after 6-hydroxytk; 1opamine (n = 8), hemodynamic tests and MIBG scintigraphy demonstrated the destruction of cardiac sympathetic innervation. Beta-adrenergic density increased by 190% (p < 0.001) while MR density remained unchanged. Three to 7 wk after surgery (n = 5), hemodynamic tests and MIBG scintigraphy demonstrated both parasympathetic and sympathetic denervations. Beta-adrenergic density was increased by 219% while MR concentration remained unchanged. Twenty-three to 28 wk after surgery, atrial innervation was restored (hemodynamic tests) while ventricular sympathetic innervation was not (MIBG scintigraphy). Beta-adrenergic density remained high. CONCLUSION: The present study demonstrates the ability of PET to serially assess myocardial receptor concentrations. The absence of change in MR density and the prolonged up-regulation of beta-AR following heart denervation are the main findings of the present study.

3-Iodobenzylguanidine↗
PubMed1994

Canine myocardial dihydropyridine binding sites: a positron emission tomographic study with the calcium channel inhibitor 11C-S11568.

The in vivo determination of the density of dihydropyridine (DHP) binding sites will allow the assessment of pathophysiological changes associated with heart disease. The calcium channel antagonist S 11568: (+/-)(amino-7 dioxa-2,5 heptyl)-2(dichloro -2,3 phenyl) -4 methyl-6dihydro -1,4 pyridine has an in vitro profile of high potency and of high selectivity for the L-type Ca2+ channel. S 11568 was labelled by a reaction between 11C-diazomethane and the precursor 6-(7-amino-2,5-dioxa heptyl)-4-(2,3-dichloro phenyl)-5-(ethoxycarbonyl)-2 methyl-1,4 dihydro nicotinic acid. (+)-PN 200 110, a DHP with in vitro high affinity for the L-type Ca2+ channel, was also radiolabeled. Positron emission tomographic (PET) studies of both 11C-DHP myocardial uptake were performed in Beagle dogs. 11C-(+)-PN 200 110 had a rapid wash-out from myocardium. In contrary, after a bolus injection, 11C-S 11568 myocardial concentration increased to reach a maximum in 1-2 minutes and then remained in a plateau with a slight downslope while the blood concentration fell rapidly. Myocardial uptake was 2 to 4 fold higher than lung uptake, leading to a good contrast on PET images. Pre-treatment with unlabeled S 11568 (2 mumol/kg or 6 mumol/kg over 15 minutes) reduced myocardial uptake by 60% and 80%, respectively. Specific binding was estimated during a displacement experiment: bolus of unlabeled S 11568: 1 mumol/kg followed by a continuous infusion of 3 mumol/kg over 2 hours. It was found to represent 80% of the total binding. To assess influence of S 11568 on coronary blood flow and therefore on the myocardial tracer delivery, coronary blood flow was measured using 15O-H2O and PET at baseline and following bolus injections of 0.4, 0.8, 2 mumol/kg of S 11568. Only the higher dose increased coronary blood flow. This is the in vivo demonstration of the binding characteristics to myocardial tissue of a DHP ligand. Such properties make S 11568 suitable for PET experiments. The studies of DHP binding sites will provided new insights concerning physiological situations as well as heart disease.

Animals↗
PubMed1994

Preparation and pharmacological characterization of [76Br]-meta-bromobenzylguanidine ([76Br]MBBG).

[76Br]-meta-Bromobenzylguanidine ([76Br]MBBG) was prepared from the iodinated analog (MIBG) and [76Br]NH4 using a Cu(+)-assisted halogen exchange reaction. [76Br]MBBG was produced in a 60-65% radiochemical yield with a specific activity of 20 MBq/nmol. In rats, biodistribution kinetic studies showed a high uptake of [76Br]MBBG in heart tissues with its maximum of 5% ID/S at 2 h p.i.; whereas 4 h p.i., the maximum of the heart-to-lung concentration ratio of 8 was observed. Metabolic studies in rats indicated that [76Br]MBBG was rapidly metabolized in plasma. However in heart tissue, 25 h p.i., 85% of the radioactivity still represented unchanged radiotracer. Pharmacological studies in rats showed that the myocardial uptake of [76Br]MBBG was similar to that of norepinephrine. After pretreatment of the rats, the uptake of [76Br]MBBG was reduced 4 h p.i. to the following values: after desipramine (DMI) to 37%, after dexamethasone (DXM) to 88% and after 6-hydroxydopamine (6-OHDA) to 16%. These preliminary results suggest that [76Br]MBBG can be useful for the assessment of heart catecholamine reuptake disorders with PET.

Animals↗
PubMed1994

In vivo quantification of myocardial muscarinic receptors in heart transplant patients.

BACKGROUND: Decreased myocardial adenylate cyclase activity in response to guanine nucleotide stimulation has been recently demonstrated in denervated myocardium of transplant patients, suggesting that changes in left ventricular muscarinic receptors may occur. METHODS AND RESULTS: The concentration and affinity constants of myocardial muscarinic receptors were determined by positron emission tomography with 11C-labeled methylquinuclidinyl benzilate (MQNB), a specific hydrophilic antagonist, in six transplant patients 4.7 +/- 2.3 months after surgery and in six normal subjects. Patients had no sign of cardiac rejection at endomyocardial biopsy. After intravenous injections of MQNB, time-activity curves were obtained over different regions of interest and were fitted to a nonlinear mathematical model. No difference in the concentration of muscarinic receptors was found in transplant patients compared with control subjects: 24 +/- 4 versus 26 +/- 7 pmol/mL tissue, respectively (P = NS). The association rate constant k+1, the dissociation rate constant k-1, and thus the equilibrium-dissociation constant Kd were the same in transplant patients compared with control subjects. CONCLUSIONS: Despite known decreased GTP-stimulated adenylate cyclase activity in transplant patients, the density and affinity constants of myocardial muscarinic receptors are not altered. This suggests abnormalities of the signal-transduction function, such as a change in the guanine nucleotide binding proteins.

Adult↗
PubMed1993

Follow-up thallium-201 scintigraphy after mantle field radiotherapy for Hodgkin's disease.

PURPOSE: Assessment of the long-term cardiac effects of mediastinal radiotherapy for Hodgkin's disease, by Thallium scintigraphy. METHODS AND MATERIALS: 32 patients (14 males and 18 females) who underwent mantle field radiotherapy for Hodgkin's disease were included in this study. Twenty patients received 4 fractions of 2.5 Gy per week and 12, five fraction of 2 Gy per week, delivered on alternate days. All the patients, except three, performed exercise testing electrocardiogram and Thallium-201 tomoscintigraphy. The average time interval from completion of treatment to the study was 7 years (range 3-13 years). No patients had clinical symptoms of cardiac disease. Mean age at the time of the study was 35 years (range 23-48 years). RESULTS: Two electrocardiograms revealed left bundle branch block and the patients were excluded from the study. Only one out of 27 exercise electrocardiograms was abnormal in a patient with mitral valve prolapse, who was also excluded from the study. Twenty-six scintigraphies were evaluable. Twenty-two (85%) were clearly abnormal with partial or complete redistribution on delayed images. The anterior region was affected in 19 of these cases (86%). Four explorations were undoubtedly normal. Coronary angiography was not performed for ethical reasons in these asymptomatic patients. CONCLUSION: Despite possible false positive tests, the high rate of abnormality (85%) in this small series is striking. These preliminary data justify larger studies and a close long-term follow-up of these patients.

Adult↗
PubMed1993

Positron emission tomography with 11C CGP-12177 to assess beta-adrenergic receptor concentration in idiopathic dilated cardiomyopathy.

BACKGROUND: Positron emission tomography (PET) with 11C-labeled CGP-12177 (CGP) has been shown to have the potential to noninvasively measure beta-adrenergic receptor concentration in dog heart. The present study was undertaken to evaluate the clinical value of this technique. METHODS AND RESULTS: Eight normal subjects and 10 patients with heart failure related to an idiopathic cardiomyopathy were studied. Estimation of beta-receptor concentration was based on a graphic method applied on myocardial PET time-concentration curves obtained after an intravenous injection of 11C-CGP followed 30 minutes later by a coinjection of labeled and unlabeled CGP. The clinical tolerance of these injections was good. Left ventricular concentration of beta-receptors was decreased in patients compared with controls (3.12 +/- 0.51 versus 6.60 +/- 1.18 pmol/mL, respectively; p < 0.001). This 53% decrease agrees with previous in vitro data. In eight of the 10 patients, the beta-receptor concentration obtained from PET was compared with the beta-receptor density determined on left ventricular endomyocardial biopsy samples by in vitro binding technique using 3H-CGP-12177. Results obtained with both techniques were correlated (r = 0.79, p = 0.019). Moreover, decreased beta-receptor concentration correlated with the beta-contractile responsiveness to intracoronary dobutamine infusion (r = 0.83, p = 0.003), indicating a direct link between changes in the receptor number and its biological function. CONCLUSIONS: PET appears to be a safe and reliable method of assessing in vivo changes in the number of left ventricular beta-adrenergic receptor sites of patients with idiopathic cardiomyopathy.

Adrenergic beta-Antagonists↗
PubMed1993

Assessment of coronary reserve in man: comparison between positron emission tomography with oxygen-15-labeled water and intracoronary Doppler technique.

This study compared positron emission tomography (PET) using oxygen-15-labeled water for measurement of coronary reserve with intracoronary Doppler in patients with left anterior descending artery stenosis and patients with no coronary lesion and a coronary reserve 3 as assessed by the invasive technique. To determine whether PET measurement of coronary reserve is altered by partial volume effect, patients with left ventricular dysfunction due to idiopathic cardiomyopathy were studied with both techniques. Direct ultrasonic measurement of coronary reserve was performed the day prior to the PET study: a Doppler catheter was placed in the proximal left anterior descending artery; mean velocity was recorded at baseline and after dipyridamole administration. Using a time-of-flight PET system, patients underwent: (1) an intravenous bolus of oxygen-15-labeled water at baseline and 4 to 6 min after intravenous infusion of dipyridamole using the same protocol as for Doppler study and (2) a 18F-fluorodeoxyglucose (FDG) myocardial imaging. Oxygen-15 time-activity curves were recorded in myocardial regions of interest (ROIs) drawn on a static FDG image. Using the left ventricular time-activity curve as an input function, a standard model with a single-tissue compartment was fitted to the PET data; myocardial blood flow was estimated as the blood-to-tissue transfer rate constant. Coronary reserve measured by PET was well correlated with the measured by intracoronary Doppler (r = 0.98, p < 0.001 for global population). This PET method is an accurate and reliable tool to noninvasively measure coronary reserve in patients, even in those with left ventricular dysfunction.

Blood Flow Velocity↗
PubMed1993

Correction of attenuation in SPECT with an attenuation coefficient map: a new method.

Attenuation coefficient (mu) maps, measured from transmission scan, are now becoming available. A simple method of attenuation correction is needed for routine implementation, however. Significant attenuation compensation can be mathematically obtained by dividing each actual pixel value of emission projections by the average of all the attenuation factors [exp (-sigma mu)] of all voxels along the same projection ray. This simple method, compatible with filtered back projection algorithms, was tested on simulations of cardiac and cerebral transaxial images on a Vax computer using the RECLBL library. In the models, the different structures received different activity and mu values. Three types of emission projections were generated: the ideal projections obtained by summation of the activity along each projection ray, the corresponding attenuated projections, and the projections corrected for attenuation. Comparison of projections on a pixel by pixel basis showed differences of less than 20% between the corrected and ideal projections. After reconstruction, both absolute and relative quantification were greatly improved by the correction of attenuation. Further validation of the method is in progress with actual patient data.

Algorithms↗
PubMed1993

Bromine-76-metabromobenzylguanidine: a PET radiotracer for mapping sympathetic nerves of the heart.

Iodine-123-metaiodobenzylguanidine (MIBG) is used to qualitatively assess heart innervation with single-photon emission computed tomography (SPECT). This approach is clinically useful in the prognostic evaluation of congestive heart failure. To improve quantification of uptake of the tracer using positron emission tomography (PET), we studied the characteristics of the bromoanalog of MIBG. Bromine-76-metabromobenzylguanidine (76Br-MBBG) was prepared from a heteroisotopic exchange between radioactive bromine atoms (noncarrier-added (76Br) BrNH4) and the cold iodine atoms of the precursor metaiodobenzylguanidine. Biodistribution was studied in rats and PET cardiac imaging performed in dogs. Myocardial uptake was high and prolonged in both species (mean half-life in dogs: 580 min). In rats, myocardial uptake was inhibited by desipramine by 64%, whereas after pretreatment with 6-hydroxydopamine uptake was reduced by 84%. In dogs pretreated with 6-hydroxydopamine or with desipramine, a steep washout of the tracer occurred (mean half-life: 136 min and 118 min, respectively). The non-specific uptake plus the passive neuronal diffusion of the tracer could be estimated at about 25%-30% of the total fixation. In dogs, analysis of unchanged 76Br-MBBG in plasma showed that radiotracer metabolism was slow: 60 min after injection, 80% of the radioactivity was related to unchanged 76Br-MBBG. These preliminary findings suggest that 76Br-MBBG could be used to quantitatively assess adrenergic innervation in heart disease using PET. When combined with use of 11C-CGP 12177, cardiac adrenergic neurotransmission can be assessed.

3-Iodobenzylguanidine↗
PubMed1992

Myocardial perfusion damage after mediastinal irradiation for Hodgkin's disease: a thallium-201 single photon emission tomography study.

Conflicting data have been reported on the incidence of myocardial abnormalities after mediastinal irradiation for Hodgkin's disease. We studied myocardial perfusion in 31 clinically asymptomatic patients (13 male, 18 female, mean age 35 years) 7 years (range 3-11 years) after mantle field radiotherapy. Thallium-201 tomoscintigraphic data were obtained after exercise, 4 h later and at rest (8-15 days later). Images were analysed visually and quantitatively (sectorial quantification of 201Tl uptake on the bull's eye images of the short-axis slices) compared with those of 35 subjects with a low likelihood of coronary artery disease. Twenty-five tomographic data sets were available. Images were visually abnormal in 21 patients (84%) showing an heterogeneous 201Tl uptake. In 68%, the sectorial 201Tl uptake was lower than the mean 201Tl uptake value minus 2 standard deviations measured in subjects with a low likelihood of coronary artery disease. Significant redistribution (quantitatively assessed > or = 10%) was present in 10 patients (40%). In most of the patients, the location and the shape of the defect(s) could not be anatomically related to an epicardial coronary vessel disease. These results indicate that after mediastinal irradiation the 201Tl myocardial uptake is frequently abnormal. The observed patterns suggest a disease of the small coronary vessels and/or the existence of a myocardial fibrosis rather than epicardial coronary artery disease.

Adult↗
PubMed1992

Myocardial beta-adrenergic desensitization and neuronal norepinephrine uptake function in idiopathic dilated cardiomyopathy.

Desensitization of myocardial beta-adrenergic receptors may result both from an impairment of the norepinephrine (NE) neuronal uptake function and from an increase in circulating NE concentrations. The respective role of these two mechanisms of desensitization was examined in 18 patients with congestive heart failure related to an idiopathic dilated cardiomyopathy. The neuronal NE uptake system was evaluated by [123I]metaiodobenzylguanidine (MIBG) scintigraphy. The desensitization level of beta-adrenoceptors was assessed as the net increase in peak positive left ventricular (LV) dP/dt during intracoronary dobutamine infusion. Arterial NE concentrations were determined at baseline. To obtain control values, we performed MIBG scintigraphy and determined baseline NE concentration in 12 normal subjects. Cardiac MIBG uptake was significantly decreased in patients as compared with controls. This decrease was related to the severity of the disease based on hemodynamic indexes. The inotropic response to intracoronary dobutamine infusion of heart failure patients correlated with both increased baseline NE concentration and diminished cardiac MIBG uptake (r = -0.63, p less than 0.01 and r = 0.73, p less than 0.001, respectively). These findings indicate that the desensitization process is related both to impaired neuronal NE uptake function and increased circulating NE concentrations. Moreover, a subset of 11 patients with moderate heart failure was identified who had diminished cardiac MIBG uptake but normal circulating NE concentrations. This suggests that impairment of the NE uptake function is an early mechanism of desensitization in idiopathic cardiomyopathy. Cardiac MIBG imaging may be a noninvasive means to assess severity of heart failure patients and may also be used to evaluate therapy effects on myocardial alterations of the adrenergic pathway.

3-Iodobenzylguanidine↗
PubMed1992

The value of pixel per pixel multiharmonic Fourier analysis to assess left ventricular function.

Left ventricular systolic and diastolic function can be assessed by peak ejection and filling rates and their time of occurrence. These parameters can be calculated using two different methods: from the global left ventricular time-activity curve analysed with a four harmonic Fourier fit and from each pixel time-activity curve analysed with two and three harmonics (the values being averaged over the left ventricular region of interest). In both cases, values were normalized for heart rate and end diastolic counts. A study was conducted in a series of 11 patients (six without and five with a previous myocardial infarction but a normal left ventricular function) examined at baseline and during an i.v. dobutamine infusion, at a dose known to increase both peak ejection and filling rates. During dobutamine infusion, analysis of global left ventricular time-activity curve demonstrated a statistically significant increase in both peak ejection and filling rates, but the local analysis showed a more significant increase of these parameters. To assess ventricular function, a local harmonic analysis can be used and appears to be a more sensitive approach than analysis of the global left ventricular time-activity curve. The local analysis provides spatial mapping and a histogram of the parameters which can be used as parametric images to describe systolic and diastolic function.

Dobutamine↗
PubMed1992

Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure.

The prognostic value of 123I-metaiodobenzylguanidine (MIBG) imaging was compared with that of other noninvasive cardiac imaging indices in ninety patients (mean age = 52 +/- 7 yr) suffering from either ischemic (n = 24) or idiopathic (n = 66) cardiomyopathy. Patients had different measurements taken: cardiac MIBG uptake, radionuclide left ventricular ejection fraction, x-ray cardiothoracic ratio and echographic M-Mode data. Cardiac MIBG uptake was assessed as the heart-to-mediastinum activity ratio measured on the chest anterior view image obtained 4 hr after intravenous injection. The patients then had follow-up for 1-27 mo, at which time 10 patients had transplants, 22 had died and 58 were still alive. Data from patients with transplants were not used in the analysis, in which multivariate stepwise regression discriminant analysis showed that cardiac MIBG uptake was more potent to predict survival than other indices: H/M (p less than 0.0001), x-ray cardiothoracic ratio (p = 0.0017), echographic end-diastolic diameter (p = 0.0264) and radionuclide left ventricular ejection fraction (p = 0.0301). Moreover, multivariate life table analysis showed that cardiac MIBG uptake was also the best predictor for life duration: H/M (p = 0.0001), radionuclide left ventricular ejection fraction (p = 0.0098) and x-ray cardiothoracic ratio (p = 0.0139); echographic data were not useful. Thus, cardiac MIBG imaging may be helpful for heart transplantation decision making in patients with heart failure.

3-Iodobenzylguanidine↗