Search PubMed⌕ Search

Biomedical subjects

P Merlet

Publications and source records attributed to P Merlet.

At least 55 records · Page 3Linked to original sources

Coronary vasodilating action of dobutamine in patients with idiopathic dilated cardiomyopathy.

To assess the coronary hemodynamic effects of dobutamine in patients with idiopathic dilated cardiomyopathy, dobutamine was infused at the incremental infusion rates of 25, 50, 100, and 200 micrograms/min into the left main coronary artery of nine patients undergoing cardiac catheterization. In response to dobutamine infusion, systemic hemodynamic effects were dose related. At the highest infusion rate cardiac index and left ventricular peak positive rate of rise in ventricular pressure increased from 2.33 +/- 0.54 to 2.97 +/- 0.65 L/min/m (p = 0.001) and from 690 +/- 177 to 1157 +/- 275 mm Hg/sec (p = 0.001), respectively. Left ventricular end-diastolic pressure decreased from 17 +/- 8 to 8 +/- 7 mm Hg (p = 0.001) and a trend toward decrease in left ventricular wall stress was observed (from 166 +/- 75 to 148 +/- 66 gm/cm2, not significant). Heart rate and mean arterial pressure remained unchanged. The coronary hemodynamic response to dobutamine infusion was also dose related. At the highest infusion rate coronary sinus blood flow increased from 133 +/- 35 to 179 +/- 47 ml/min (p < 0.01) and was associated with an increase in coronary oxygen blood content from 4.5 +/- 0.6 to 7.8 +/- 1.7 ml per 100 ml (p < 0.01) whereas myocardial oxygen consumption remained unchanged. During dobutamine infusion norepinephrine decreased in the femoral artery and in the coronary sinus from 1.03 +/- 0.34 to 0.641 +/- 0.179 ng/ml (p < 0.05) and from 1.76 +/- 0.98 to 1.38 +/- 0.65 ng/ml (p < 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

[Doppler echocardiographic evaluation of mitral flow velocity and prognosis of cardiac insufficiency].

The aim of this study was to determine the role of Doppler echocardiography in establishing the prognosis of Stages to 4 cardiac failure. The echocardiographic indices of left ventricular filling were correlated with catheter data and the 2 year out come of patients. The study population included 54 patients examined prospectively in the context of an evaluation of their cardiac failure. Two years after the initial examination, 19 patients were dead or transplanted. Of the remaining 35 patients, 18 were reevaluated at 6 months. Of the echocardiographic parameters, "hyper normal" mitral flow with a high E/A ration indicated poor prognosis; when E/A > 2, the one year survival was 50% and the 2 year survival 42%. There was overlap between the groups of dead or transplanted and surviving patients only when the E/A ratio was between 2 and 3. The patients with E/A < 2 were all alive without any major events at 2 years. All patients with E/A > 3 had a poor prognosis. The E/A ratio was closely correlated with pulmonary capillary pressure levels (p < 0.001, r = 0.55) and lees closely with cardiac index (p < 0.05, r = 0.4) and radionuclide ejection fraction (p < 0.05, r = 0.28). After 6 months' vasodilator treatment with an angiotensin converting enzyme inhibitor (captopril) the E/A ratio decreased significantly from 1.85 +/- 0.78 to 1.0 0.55 (p < 0.02). A "hyper-normal" mitral flow is related to many factors, including high left ventricular filling pressures, mitral regurgitation and reduced left ventricular compliance. This appearance of mitral flow is a poor prognosis factor in severe cardiac failure.

Actuarial Analysis↗

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↗

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↗

Quantification of myocardial muscarinic receptors with PET in humans.

The potential for noninvasive quantification of myocardial muscarinic receptors using PET data, a mathematical model, multi-injection protocols and 11C-labeled methylquinuclidinyl benzilate (MQNB) as a radioligand was previously demonstrated in dogs. The present study examines the possibility of optimizing the experimental protocol to make this approach suitable for human studies. For six normal subjects, the protocol included three injections: a tracer injection, followed 30 min later by an injection of an excess of unlabeled MQNB (displacement) and then 30 min later by a simultaneous injection of unlabeled and labeled MQNB (coinjection). The model input function was estimated from the PET data corresponding to the left ventricular cavity. This protocol enables a separate evaluation of all parameters of a ligand-receptor model which includes three compartments and seven parameters. The complexity of this three-injection protocol, however, appears to be inconvenient for clinical use. A simplified two-injection protocol (tracer injection and coinjection) was evaluated in five other normal subjects and the results were compared to those obtained with the three-injection protocol. In regions of interest over the left ventricle, the mean value of the receptor concentration B'max and the equilibrium dissociation constant Kd were 26 +/- 7 pmole/ml tissue and 2.0 +/- 0.5 pmole/ml tissue, respectively. The possible existence of nonspecific binding was studied in two subjects using a double-displacement protocol. The corresponding rate constant was found to be very low (0.03 min-1).

Adult↗

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Beta-adrenergic contractile reserve as a predictor of clinical outcome in patients with idiopathic dilated cardiomyopathy.

To examine the ability of beta-adrenergic contractile reserve assessment to predict the outcome of patients with heart failure, a prospective study was undertaken in 35 patients with idiopathic dilated cardiomyopathy and radionuclide ejection fraction below 40%. During right- and left-sided catheterization, right atrial and left ventricular (LV) pressures, peak positive LV dp/dt, cardiac index, and plasma norepinephrine and epinephrine concentrations were measured at baseline. After a left main intracoronary infusion of dobutamine (25 to 200 micrograms.min-1), beta-adrenergic contractile responsiveness was assessed as the net increase in peak positive LV dp/dt (delta LV dp/dt). After the initial examination, patients were treated with diuretics, digitalis, and angiotensin converting enzyme inhibitors and then followed-up. After a mean follow-up period of 13 +/- 7 months, two groups of patients were distinguished: those who responded to medical therapy (group A, n = 26) and those with clinical deterioration (group B, n = 9) leading to death (n = 4) or heart transplantation (n = 5). Initial peak positive LV dp/dt, LV end-diastolic pressure, cardiac index, and LV ejection fraction were better in group A than in group B (p less than 0.001). Initial plasma norepinephrine and epinephrine concentrations were significantly higher and delta LV dp/dt was lower in group B than in group A (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship among neuropeptide Y, catecholamines and haemodynamics in congestive heart failure.

The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was assessed both at baseline and during inotropic intervention in patients with congestive heart failure. Eighteen patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction (LVEF) = 26 +/- 10%) underwent both right and left catheterization. Haemodynamic parameters were recorded at baseline and during dobutamine infusion. To measure norepinephrine (NE), epinephrine (E) (nmol.l-1: radioenzymatic assay) and NPY (pmol.l-1: immunoradiometric assay) plasma concentrations, blood samples were drawn from the femoral artery and from the coronary sinus, both at baseline and during dobutamine infusion. At baseline, NPY concentration were 2.15 +/- 0.97 pmol.l-1 in the femoral artery and 1.97 +/- 0.63 pmol.l-1 in the coronary sinus. Peripheral concentrations of NPY were, however, no different from those of patients without congestive heart failure: 2.4 +/- 2.7 pmol.l-1. Peripheral NE concentration was correlated to haemodynamic parameters: LVEF (r = -0.65; P less than 0.01), cardiac index (r = -0.54; P less than 0.05), LV end-diastolic pressure (r = +0.59; P less than 0.05), while peripheral NPY and E concentrations were not. Dobutamine improved haemodynamics, since cardiac index increased by 30% and LV end-diastolic pressure decreased by 40% (P less than 0.01). Peripheral NE concentration decreased from 6.48 +/- 4.5 to 4.82 +/- 2.69 nmol.l-1 (P less than 0.05) but there was no change in E (0.99 +/- 0.61 vs 1.04 +/- 0.74 nmol.l-1) or NPY concentrations (2.41 +/- 0.99 pmol.l-1). In the coronary sinus, neither NE nor NPY concentrations changed during dobutamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

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↗

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↗

[Neuroendocrine adaptations in chronic congestive heart failure].

Chronic congestive heart failure is typically accompanied by an abnormal production of vasoconstrictor antinatriuretic hormones and vasodilator natriuretic hormones. Decompensation occurs when the former prevail over the latter. These neuroendocrine abnormalities are increasingly taken into account to determine the prognosis and to decide on the best therapeutic approach in individual patients with chronic heart failure.

Adaptation, Physiological↗

Ventricular function during the acute rejection of heterotopic transplanted heart: gated blood-pool studies.

Twenty patients who had undergone a heterotopic heart transplant were studied prospectively to determine the relationship between rejection and ventricular dysfunction assessed from gated blood-pool studies. A fully automated method for detecting ventricular edges was implemented; its success rate for the grafted left and right ventricles was 94% and 77%, respectively. The parameters, peak ejection and filling rates, were calculated pixel per pixel using a two-harmonic Fourier algorithm and then averaged over the ventricular region of interest. Peak filling and ejection rates were closely related with the severity of the rejection, while the left ventricular ejection fraction was not. Peak filling rates of both ventricles were the indices closely related to the presence of moderate rejection. Despite the low number of patients, these data suggested that gated blood-pool-derived indices of ventricular function are associated with ventricular dysfunction resulting from myocarditis rejection. Radionuclide ventriculography provides parametric data which are accurate and reliable for the diagnosis of rejection.

Algorithms↗

Hemodynamic response to intracoronary infusion of atrial natriuretic factor in patients with normal or altered left ventricular function.

To assess the effects of atrial natriuretic factor (ANF) on cardiac function, synthetic human ANF was infused directly into the left main coronary artery of eight patients with congestive heart failure (CHF) and six subjects with normal left ventricular (LV) function (controls) who underwent cardiac catheterization. ANF infusion at the incremental rates of 60, 125, 400, and 800 ng/min induced a dose-related increase in plasma ANF concentrations in the coronary sinus, from 1,223 +/- 590 to 3,923 +/- 1,123 pg/ml in patients with CHF (p less than 0.01) and from 1,041 +/- 605 to 2,710 +/- 1,741 pg/ml in controls (p less than 0.01). Peripheral plasma ANF concentrations (femoral artery) increased from 538 +/- 278 to 752 +/- 262 pg/ml (p less than 0.01) in patients with CHF and from 193 +/- 63 to 401 +/- 147 pg/ml (p less than 0.01) in controls. The increase in peripheral or coronary sinus plasma ANF concentrations did not differ between patients with CHF and controls. At the three lowest ANF infusion rates, cardiac index (CI), systemic vascular resistance (SVR), and LV contractility assessed by peak positive dP/dt remained unchanged both in patients with CHF and in controls. At the highest ANF infusion rate, CI increased from 2.18 +/- 0.53 to 2.54 +/- 0.49 L/min/m2 (p less than 0.01) and SVR decreased from 14.6 +/- 3.6 to 12.8 +/- 4.5 mm Hg.min/L (p less than 0.01) in patients with CHF. There was no associated change in heart rate (HR), mean arterial blood pressure (MAP), cardiac filling pressures, or peak positive dP/dt.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Physiologic assessment of milrinone therapy in severe heart failure patients.

To assess the inotropic, vasodilator, and after-load-reducing effects of intravenous milrinone in patients with severe congestive heart failure, a simple noninvasive echocardiographic study coupled with a right catheterization was performed in 12 patients. Milrinone was administered intravenously as a 50 micrograms.kg-1 bolus followed by a 24-h milrinone infusion at a rate of 0.5 mg.kg-1.min-1 [corrected]. Echocardiographic left ventricular end-diastolic diameter (Ded), end-systolic diameter (Des), and wall thickness were measured at baseline and at 24 h of milrinone infusion, before and after a sublingual nitrate administration (0.8 mg of nitroglycerin) that induced load variations. Hemodynamic measurements were performed simultaneously. Left ventricular end-systolic meridional wall stress (Ses) was then calculated. The slopes of percent fractional shortening (percent FS)/Ses and Ses/Des, obtained during sublingual nitrate administration, were traced. Both end-systolic relations are an index of the contractile state. Milrinone therapy improved hemodynamics in all patients, resulting in stabilized hemodynamic conditions between 12 and 24 h of continuous milrinone infusion. At these times, the cardiac index increased to 30% while the capillary pulmonary wedge pressure and systemic vascular resistance decreased to 26 and 24%, respectively (all p less than 0.01). The average slope of Ses/Des shifted upward from 47.5 +/- 30 to 69.25 +/- 34 (p less than 0.05) and the average slope of (percent FS)/Ses shifted from -0.032 +/- 0.025 to -0.082 +/- 0.061 (p less than 0.01), both variations attesting the inotropic effect of milrinone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Percutaneous transluminal angioplasty of the common trunk during the acute phase of myocardial infarction].

The prognosis of cardiogenic shock in the acute phase of myocardial infarction has been transformed since the introduction of techniques of myocardial revascularisation. We report the case of a patient in cardiogenic shock after a large anterior myocardial infarct in whom failure of early thrombolytic therapy led to referral for emergency percutaneous transluminal coronary angioplasty. The success of the procedure on the patient's haemodynamic condition was life-saving. The originality of this case resides in the fact that revascularisation concerned the left main coronary stem.

Angioplasty, Balloon, Coronary↗