CLINICAL STUDIES
Cardiac sympathetic innervation in patients with idiopathic right ventricular outflow tract tachycardia
Michael Schäfers, MD*  ,
Hartmut Lerch, MD*,
Thomas Wichter, MD*,
Christopher G. Rhodes, MSc,
Adriaan A. Lammertsma, PhD,
Martin Borggrefe, MD*,
Flemming Hermansen, MD,
Otmar Schober, MD, PhD*,
G.ünter Breithardt, MD, FESC, FACC* and
Paolo G. Camici, MD, FESC, FACC, FRCP
* Department of Nuclear Medicine and Department of Cardiology and Angiology and Institute for Arteriosclerosis Research, Westfälische Wilhelms University, Munster, Germany
Medical Research Council–Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital, London, England, United Kingdom
Manuscript received October 8, 1997;
revised manuscript received March 27, 1998,
accepted April 9, 1998.
Address for correspondence: Dr. Paolo G. Camici, Medical Research Council–Cyclotron Unit, Hammersmith Hospital, Ducane Road, W12 ONN, London, England, United Kingdom
paolo{at}cu.rpms.ac.uk
 |
Abstract
|
|---|
Objectives. This study investigated the neuronal reuptake of norepinephrine (uptake-1) and the beta-adrenoceptor density in patients with idiopathic right ventricular outflow tract tachycardia (RVO-VT).
Background. Clinical findings, such as the inducibility of ventricular tachycardia by stress or catecholamine infusion, and the therapeutic efficacy of antiarrhythmic drugs with antiadrenergic properties suggest abnormalities of cardiac sympathetic innervation in patients with idiopathic RVO-VT.
Methods. Eight patients with idiopathic RVO-VT and a total of 29 age-matched control subjects were investigated by positron emission tomography using [11C]hydroxyephedrine (HED) (volume of distribution of [11C]HED) to assess presynaptic norepinephrine reuptake; [11C]CGP 12177 (maximal binding capacity of [11C]CGP 12177) to measure postsynaptic beta-adrenoceptor density; and oxygen-15–labeled water for quantification of myocardial blood flow (MBF).
Results. Both myocardial catecholamine reuptake and beta-adrenoceptor density were significantly reduced in patients with idiopathic RVO-VT. The volume of distribution of [11C]HED in patients with RVO-VT was (mean ± SD) 41.0 ± 13.5 versus 71.0 ± 18.8 ml/g in control subjects (p < 0.002). The maximal binding capacity of the beta-adrenoceptor antagonist [11C]CGP 12177 was 6.8 ± 1.2 pmol/g in patients with RVO-VT versus 10.2 ± 2.9 pmol/g in control subjects (p < 0.004). There were no significant differences in MBF at rest (0.98 ± 0.14 vs. 0.97 ± 0.24 ml/min per g, p = NS) between patients with RVO-VT and control subjects.
Conclusions. The findings of the present study suggest that myocardial beta-adrenoceptor downregulation in patients with RVO-VT occurs subsequently to increased local synaptic catecholamine levels caused by impaired catecholamine reuptake.
|
Abbreviations and Acronyms
| | Bmax | = maximal binding capacity | | BGO | = bismuth germanate | | [11C]HED | = [11C]hydroxyephedrine | | MBF | = myocardial blood flow | | [123I]MIBG | = [123I]meta-iodo-benzylguanidine | | PET | = positron emission tomography (tomographic) | | ROI | = region of interest | | RVO-VT | = right ventricular outflow tract tachycardia | | Vd | = volume of distribution |
|
In 1922, Gallaverdin (1) reported repetitive monomorphic ventricular tachycardia originating in the right ventricle in patients with an otherwise apparently normal heart. Until now, despite the increasing availability of a variety of diagnostic methods, including electrophysiologic study and endomyocardial biopsy, there exists a group of patients with right ventricular tachycardia (idiopathic right ventricular outflow tract tachycardia [RVO-VT]), of which the underlying pathophysiologic mechanism is not completely known (2–4). Typically affecting young patients, RVO-VT causes palpitation, dizziness, syncope and, sometimes, sudden cardiac death (5). RVO-VT is characterized by commonly provocable tachyarrhythmias under physical exercise conditions, first described by Wilson et al. (6) in 1932, or by catecholamine infusion during electrophysiologic studies (7). Typically, the tachycardias can be suppressed by an antiarrhythmic drug regimen with antiadrenergic properties, which is suggestive of an involvement of the cardiac sympathetic nervous system in the pathophysiology of RVO-VT (8). Regional alteration of the presynaptic reuptake of norepinephrine (uptake-1) associated with ventricular arrhythmia has been suggested on the basis of reduced uptake of the norepinephrine analogue [123I]meta-iodo-benzylguanidine ([123I]MIBG) in other diseases without structural abnormalities of the heart (9–11), and in arrhythmogenic right ventricular cardiomyopathy (12), global alteration of presynaptic function measured by [3H]norepinephrine spillover was found in patients with sustained ventricular tachyarrhythmias and coronary artery disease (13).
On the basis of these studies, we hypothesized that presynaptic reuptake of norepinephrine may be reduced in RVO-VT, which in turn would lead to an increased concentration of norepinephrine in the synaptic cleft and downregulation of the postsynaptic beta-adrenoceptors. To test this hypothesis, we assessed presynaptic uptake-1 and postsynaptic beta-adrenoceptor density in the myocardium of patients with idiopathic RVO-VT by means of positron emission tomography (PET) with the norepinephrine analogue [11C]hydroxyephedrine ([11C]HED) (14) and the beta-antagonist [11C]CGP 12177 (15) (Fig. 1).
View larger version (18K):
[in this window]
[in a new window]
|
Figure 1 Scheme of presynaptic and postsynaptic sympathetic innervation. The norepinephrine (NE) analogue [11C]HED was used for measuring presynaptic reuptake of norepinephrine (UP), and the nonselective beta-blocker [11C]CGP 12177 was used for measuring postsynaptic beta-adrenoceptor (ß-AR) density.
|
|
|
Methods
|
|---|
Subjects.
Study patients
Eight patients (six women, two men; mean ± SD age 44 ± 11 years, range 26 to 55, median 49) with documented recurrent RVO-VT were investigated.
Patient characterization
RVO-VT was diagnosed on the basis of documented sustained or nonsustained ventricular tachycardia of left bundle branch block configuration and inferior QRS axis originating in the right ventricular outflow tract as determined by the configuration of ventricular tachycardia and by endocardial mapping during an electrophysiologic study. Two-dimensional echocardiography, left and right ventricular angiography, coronary angiography and endomyocardial biopsy were performed to exclude morphologic, functional and structural heart disease, including coronary artery disease, hypertrophic or dilated cardiomyopathy; and congenital, valvular and inflammatory heart disease (3,5). All patients were in sinus rhythm with normal 12-lead electrocardiograms at rest. In particular, no patient had bundle branch block, left ventricular hypertrophy or a prolongation of the QT interval. Signal-averaged electrocardiograms were normal in all patients (16). All patients underwent an invasive electrophysiologic study, including programmed ventricular stimulation with up to three extrastimuli and additional isoproterenol infusion (12,17). Ventricular tachycardia was sustained in two patients (25%). Monomorphic ventricular tachycardia was provocable by physical exercise in six patients and by intravenous isoproterenol infusion in four (Table 1).
Control groups
Two groups of age-matched control subjects were studied. For the studies with [11C]HED and oxygen-15–labeled water (H2[15O]), the control group included 10 subjects (mean age 35 ± 7 years, range 23 to 46, median 33, p = NS vs. patients). For the [11C]CGP 12177 scans, a control group of 19 volunteers (mean age 44 ± 16 years, range 21 to 65, median 45, p = NS vs. patients) was investigated. All control subjects had no history of cardiac disease, a low risk profile and normal examination results. All had normal rest ECGs and negative exercise tests in response to a high workload.
Informed consent
All study patients and control subjects gave written informed consent to the study protocol, which was approved by the Hammersmith Hospital Research Ethics Committee and the United Kingdom Administration of Radioactive Substances Advisory Committee (ARSAC).
Study protocol.
Subject preparation
Measurement of cardiac presynaptic and postsynaptic sympathetic function was performed in the same subject on 2 consecutive days. The patients took no medication for at least 24 h. No patient had previously received beta-adrenergic blocking agents.
Data acquisition
Cardiac presynaptic norepinephrine reuptake and postsynaptic beta-adrenoceptor density were assessed by dynamic positron emission tomography (PET) (ECAT 931-08/12, Siemens/CTI) using the norepinephrine analogue [11C]HED and the nonselective ( 80% beta1) hydrophilic beta-adrenoceptor antagonist [11C]CGP 12177 (4-(3-t-butylamino-2-hydroxypropoxy)-benzimidazol-2-1) (15). In addition, rest myocardial blood flow (MBF) was assessed using H2[15O] (18).
The left ventricle was centered in the field of view by means of a rectilinear scan recorded during the exposure of external germanium-68 ring sources. This was followed by a transmission scan of 20 min in duration for attenuation correction. A blood volume scan (ml blood/ml region of interest) was then performed using inhalation of oxygen-15–labeled carbon monoxide (C[15O]) delivered through a face mask at a constant rate of 500 ml/min and a radioactive concentration of 3 MBq/ml over 4 min. After 1 min, to allow for tracer equilibration, a 6-min emission scan was initiated, during which four venous blood samples were taken to measure blood radioactivity.
Day 1
Presynaptic norepinephrine reuptake was measured by intravenous administration of [11C]HED prepared by direct N-methylation of metaraminol with [11C]methyliodide in sulfoxide (14). The compound was purified using high performance liquid chromatography to provide an isotonic buffered aqueous solution for injection with high specific activity, resulting in low injectate levels of HED and precursor (3.2 ± 1.7 and 0.5 ± 0.3 µg, respectively) and a radiochemical purity >99.5%. [11C]HED (352 ± 36 MBq) was infused intravenously over a period of 1 min. The amount of injected (radioactive and molar) HED was not different between patients and control subjects. During the dynamic scan of 65 min (frames: 1 x 30 [background], 6 x 5, 6 x 10, 3 x 20, 4 x 30, 5 x 60, 4 x 150 and 9 x 300 s), arterialized venous blood was sampled at a rate of 2.5 ml/min from the vein of a heated hand by means of a peristaltic withdrawal pump and a bismuth germanate (BGO) detection system for monitoring the arterial input function (19). Additional samples of arterialized blood were taken to calibrate the BGO detection system, measure whole blood/plasma ratios and assay HED metabolites in plasma. MBF was measured by an intravenous bolus of 555 MBq H2[15O] (frames: 1 x 30, 1 x 20, 14 x 5, 3 x 10, 3 x 20, and 4 x 30 s) (18).
Day 2
Postsynaptic beta-adrenoceptor density was assessed using [11C]CGP 12177, as previously described (20–22). Briefly, a first dose of [11C]CGP 12177 with high specific activity (161.8 ± 26.4 MBq, 5.4 ± 1.9 µg of cold CGP 12177) was infused intravenously over 2 min (frames: 1 x 30 [background], 8 x 15, 4 x 30, 2 x 60, 2 x 120 and 8 x 150s). Thirty minutes later, a second dose with low specific activity (311.7 ± 63.5 MBq, 27.7 ± 6.7 µg of cold CGP 12177) was infused intravenously over 2 min (frames: 8 x 15, 4 x 30, 2 x 60, 2 x 120 and 14 x 150 s). The amount of CGP 12177 injected (radioactive and molar) was not different between patients and control subjects. Venous blood was sampled from the antecubital vein using the BGO detection system, as described earlier. Additional blood samples were taken to calibrate the BGO detection system and to measure whole blood/plasma ratios at 10, 25, 45, 60 and 75 min after injection.
Data analysis
Raw scan data were stored on a MicroVax II computer (Digital Equipment Corporation), then transferred to a SUN workstation for normalization, attenuation correction and reconstruction. The resulting images were further analyzed using software developed under the MatLab mathematical software package (The MathWorks Inc.). Images were resliced by defining the heart axis in the vertical and horizontal long-axes views. Twelve slices were defined between the visually defined base and apex of the heart to obtain anatomically standardized regions. On the short-axis slices, inner and outer myocardial borders were traced manually. Sixteen ROIs were automatically defined for regional analysis. For the analysis of the whole left ventricle, all regions were grouped together. In addition, regions were drawn within the left atrium on at least three consecutive planes for arterial input data. All ROIs were then applied to all dynamic emission images to generate time–activity curves.
Myocardial blood volume
Myocardial blood volume (ml/ml ROI) was determined by relating the regional concentration of radioactivity in the C[15O] scan to the mean concentration of radioactivity in the blood samples (a value of 1.06 g/ml was assumed for the density of blood). Extravascular tissue volume (ml tissue/ml ROI) was calculated by subtracting the vascular density image from the normalized transmission scan (18).
MBF
MBF was calculated using a single-compartment model (18). From the H2[15O] scan data, the perfused tissue fraction (ml exchangable tissue/ml ROI) was calculated to correct the [11C]HED scan for partial volume effects.
Presynaptic neuronal norepinephrine reuptake
Uptake-1 was assessed by the volume of distribution (Vd) of [11C]HED using a single-tissue compartment model and least-square nonlinear regression to provide influx and efflux rate constants K1 and k2, where  . The arterial input function was obtained from the left atrium for the first 15 min after the start of injection and from the BGO counting system afterward. This was necessary because of the net extraction of tracer from blood in the heated hand in the first phase and the low blood count rate and increasing myocardial spillover into the left atrial ROI at later times. The later part of the BGO curve was used to correct for the spillover of radioactivity into the left atrium. Plasma metabolite concentrations were determined by high performance liquid chromatography and used to correct the plasma [11C]HED input curves. The resulting values of Vd (ml/ml ROI) were regionally corrected for partial volume and heart motion effects using the measured values of tissue fraction obtained from the MBF scan. These values were then converted from units of ml/ml to units of ml/g by dividing by the myocardial tissue density (1.04 g/ml tissue).
Postsynaptic beta-adrenoceptor density
Adrenoceptor density was estimated by measurement of the maximal binding capacity (Bmax) (pmol/g) of the beta-adrenoceptor antagonist [11C]CGP 12177. The two sections of the curve corresponding to the slow clearance of tracer from tissue, which represent the dissociation of [11C]CGP 12177 bound to beta-adrenoreceptors after each injection, were exponentially extrapolated on the y-axis back to the start of each infusion. Bmax was calculated using a modification of the equation described by Delforge et al. (20) to take account of the molar content of [11C]CGP 12177 in both injections (21,22). Time–activity curves were corrected for decay and spillover of radioactivity from blood to the myocardium using the blood volume image and the blood time–activity curves. Bmax was corrected for the partial volume effect by normalizing it to the regional values of extravascular tissue volume (ml tissue/ml ROI) obtained from the blood volume and transmission scans. The myocardial beta-adrenoceptor density values were then converted from units of pmol/ml tissue to pmol/g tissue by dividing it by the density of myocardial tissue (1.04 g/ml tissue).
Hemodynamic variables and plasma norepinephrine
During the scans, heart rate, heart rhythm (12-lead ECG) and blood pressure were monitored at 15-min intervals. Plasma norepinephrine was measured at the beginning and end of each scanning procedure.
Statistical analysis.
Results are expressed as mean value ± standard deviation. After testing for the equality of variances (Levene test, SPSS), the Student t test was used for the comparison between groups for the values of Vd of [11C]HED, Bmax of [11C]CGP 12177, MBF and hemodynamic and serum variables. The coefficient of variation was used to test for regional differences of left ventricular distribution of [11C]HED and [11C]CGP 12177. A p value of 0.05 was considered significant.
|
Results
|
|---|
Hemodynamic variables and plasma norepinephrine.
There were no differences between patients and control subjects concerning heart rate and systolic and diastolic blood pressure at baseline and during the scans. A 12-lead ECG recording confirmed the absence of ventricular tachycardia during scanning in all patients. Plasma norepinephrine levels were constant during the scans and were not different from those in the control group (1.20 ± 0.61 vs. 1.41 ± 0.68 nmol/liter, p = NS).
MBF.
Whole-heart MBF was similar in patients and control subjects (0.98 ± 0.14 vs. 0.97 ± 0.24 ml/min per g, p = NS), and no regional differences were observed in either group.
Myocardial sympathetic function.
Global Vd of HED and Bmax of CGP 12177 were significantly reduced in patients with RVO-VT compared with that in control subjects (Vd of HED 41.0 ± 13.5 vs. 71.0 ± 18.8 ml/g, p < 0.002; Bmax of CGP 12177 6.8 ± 1.2 vs. 10.1 ± 2.9 pmol/g, respectively, p < 0.004) (Fig. 2 and 3). There was no significant correlation between presynaptic and postsynaptic function in each patient (r = 0.38, p = NS). No regional differences in the Vd of HED and Bmax of CGP 12177 were observed in either group.
View larger version (17K):
[in this window]
[in a new window]
|
Figure 2 Norepinephrine reuptake measured by Vd of [11C]HED in patients with RVO-VT and control subjects (mean value is indicated by horizontal lines).
|
|
View larger version (16K):
[in this window]
[in a new window]
|
Figure 3 Bmax for beta-adrenoceptors measured using [11C]CGP 12177 in patients with RVO-VT and control subjects (mean value is indicated by horizontal lines).
|
|
|
Discussion
|
|---|
The most likely pathophysiologic mechanism of ventricular tachycardia in patients with idiopathic RVO-VT is a cyclic adenosine monophosphate–dependent increase in intracellular Ca ions, with subsequent delayed afterdepolarization (23,24). This is supported indirectly by the proarrhythmic effect of beta-adrenergic agonists (e.g., isoproterenol), which stimulate adenylyl cyclase activity, as well as by the finding that tachycardia can be terminated by substances such as adenosine, which inhibit adenylyl cyclase. In the present study, we showed that presynaptic reuptake of norepinephrine and postsynaptic beta-adrenoceptor density are globally reduced in the left ventricular myocardium of patients with RVO-VT and that, in the same subjects, myocardial perfusion at rest was normal. Reduced catecholamine reuptake and beta-adrenoreceptor density have also been described in different forms of cardiomyopathies and postischemic heart failure as well as in dysautonomias (25–31). In these diseases, the changes in presynaptic and postsynaptic sympathetic innervation are probably consequent to the functional and structural abnormalities of the heart. In contrast, in patients with idiopathic RVO-VT, no functional or structural abnormality is detectable: patients with RVO-VT typically show no sign of heart failure and exhibit normal plasma norepinephrine levels (23). The same investigators found an increased sympathetic activity before the onset of arrhythmias in patients with RVO-VT, by analysis of heart rate variability without changes in parasympathetic activity. A local increase in norepinephrine in the synaptic cleft can in theory be explained by two mechanisms: 1) an increase in presynaptic release, and 2) a reduced presynaptic reuptake (uptake-1) (32). The finding of the present study, that the Vd of [11C]HED is significantly reduced does not allow discrimination between increased neuronal release and reduced reuptake. In fact, the Vd of [11C]HED, which is defined as the ratio of neuronal influx and efflux, can be reduced because of decreased influx (uptake-1) or increased efflux (neuronal release) (32).
The reduced density of myocardial beta-adrenoceptors demonstrated by PET in the present study is consistent with an increased concentration of norepinephrine in the synaptic cleft. Ventricular tachycardia in patients with RVO-VT can be triggered by exercise, which is accompanied by increased sympathetic activity, or by direct catecholamine administration (7). This finding suggests that despite beta-adrenoceptor downregulation, norepinephrine is still capable of increasing significantly the intracellular cyclic adenosine monophosphate concentration, probably due to changes in the beta-adrenoceptor–G-protein–adenylyl cyclase pathway (Fig. 4) (33).
View larger version (20K):
[in this window]
[in a new window]
|
Figure 4 Hypothetic pathophysiologic mechanism of tachycardia in patients with idiopathic RVO-VT. Reduced reuptake (UP) of norepinephrine (NE) into the nerve terminal or increased release (RE) into the synaptic cleft leads to an increase in local norepinephrine concentration in the synaptic cleft and stimulation of postsynaptic beta-adrenoceptors (ß-AR). In turn this leads to increased cyclic adenosine monophosphate (cAMP) through activation of the stimulatory G protein (GS) and adenylyl cyclase (AC). The increase in cAMP will produce a rise in intracellular Ca2+ levels by activation of protein kinase A (PKA) and will eventually trigger ventricular tachycardia. That this occurs despite beta-adrenoceptor downregulation suggests that norepinephrine is still capable of significantly increasing intracellular cAMP concentration, probably due to changes in the beta-adrenoceptor–G-protein–adenylyl cyclase pathway.
|
|
Study limitations.
The important link between presynaptic and postsynaptic adrenergic function, namely, the norepinephrine concentration in the synaptic cleft, cannot be measured noninvasively in vivo. Because neither norepinephrine spillover nor efferent sympathetic activity, (e.g., by means of microneurography) was measured in the present study, the existence of locally high catecholamine concentrations in the synaptic cleft as the primary cause of beta-adrenoceptor downregulation in our patients with RVO-VT cannot be proved.
Because of the limited spatial resolution of the PET scanner, it was not possible to perform accurate measurements in the thin right ventricular wall. Therefore, we could not ascertain whether presynaptic and postsynaptic sympathetic nerve function were abnormal in the right ventricle, which is known to be the origin of the arrhythmia in these patients (3). Preliminary studies in conscious dogs (34) submitted to rapid right ventricular pacing for 1 day demonstrated a significant increase in efferent sympathetic activity directed to the heart that was abolished by selective left ventricular denervation. This finding suggests that a stimulus originating from the right ventricle can be associated with an increased efferent activity to the whole heart and is in line with the findings of the present study.
Regional sympathetic denervation, previously shown by [123I]MIBG in 70% of patients (11), was not confirmed in the present investigation. However, no patient in the present study was previously investigated with [123I]MIBG, and therefore a direct comparison is not possible.
Although the number of patients studied is small, they represent a carefully selected cohort because patients with previous treatment with beta-blockers or undergoing catheter ablation were excluded.
Conclusions.
The results of the present study show that in patients with idiopathic RVO-VT, both presynaptic catecholamine reuptake and postsynaptic beta-adrenoceptor density are reduced. These findings support previous results of locally increased sympathetic activity, most likely due to increased local catecholamine levels in the synaptic cleft, and may play a role in the pathophysiology of the tachycardia.
|
Acknowledgments
|
|---|
We are grateful to the staff of the MRC Cyclotron Unit; especially the members of the radiochemistry section for the production of the radiopharmaceuticals, the radiographers for performing the studies, the blood laboratory group for blood and metabolite analysis and Daniella Muallem for assistance with the data analysis of the HED scans.
|
Footnotes
|
|---|
This study was supported in part by Grants Wi 1412/1-1 and Le 999/1-1 from the Deutsche Forschungsgemeinschaft, Bonn, Germany.
|
References
|
|---|
1. Gallaverdin L. Extrasystolie ventriculaire a paroxysmes tachycardiques prolonges. Arch Mal Coeur. 1922;15:298
2. Belhassen B, Viskin S. Idiopathic ventricular tachycardia and fibrillation. J Cardiovasc Electrophysiol. 1994;4:356–368
3. Wichter T, Breithardt G, Borggrefe M. Ventricular tachycardia in the normal heart. Podrid PJ, Kowey PR. Cardiac Arrhythmias: Mechanisms, Diagnosis and Management. Baltimore: Williams & Wilkins; 1995. p. 1219–1238
4. Klug D, Ferracci A, Molin F, et al. Body surface potential distributions during idiopathic ventricular tachycardia. Circulation. 1995;91:2002–2009[Abstract/Free Full Text]
5. Breithardt G, Borggrefe M, Wichter T. Editorial comment: catheter ablation of idiopathic right ventricular tachycardia. Circulation. 1990;82:2273–2276[Free Full Text]
6. Wilson FN, Wishart SW, Macleod AG, Barker PS. A clinical type of paroxysmal tachycardia of ventricular origin in which paroxysms are induced by exertion. Am Heart J. 1932;8:155–169[CrossRef]
7. Kienzle MG, Martins JB, Constantin L, Aschoff A. Effect of direct, reflex and exercise-provoked increases in sympathetic tone on idiopathic ventricular tachycardia. Am J Cardiol. 1992;69:1433–1438[CrossRef][Medline]
8. Zipes DP. Sympathetic stimulation and arrhythmias. N Engl J Med. 1991;325:656–657[Medline]
9. Gill JS, Hunter GJ, Gane J, Ward DE, Camm AJ. Asymmetry of cardiac 123I-meta-iodobenzylguanidine scans in patients with ventricular tachycardia and a "clinically normal" heart. Br Heart J. 1993;69:6–13[Abstract/Free Full Text]
10. Mitrani R, Klein LS, Miles WM, et al. Regional cardiac sympathetic denervation in patients with ventricular tachycardia in the absence of coronary artery disease. J Am Coll Cardiol. 1993;22:1344–1353[Abstract]
11. Schafers M, Wichter T, Lerch H, et al. Cardiac sympathetic dysfunction in idiopathic ventricular tachycardia and fibrillation. J Nucl Med. In press.
12. Wichter T, Hindricks G, Lerch H, et al. Regional myocardial sympathetic dysinnervation in arrhythmogenic right ventricular cardiomyopathy. Circulation. 1994;89:667–683[Abstract/Free Full Text]
13. Meredith IT, Broughten A, Jennings GL, Esler MD. Evidence of selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias. N Eng J Med. 1991;325:618–624[Medline]
14. Rosenspire KC, Haka MS, van Dort ME, et al. Synthesis and preliminary evaluation of carbon-11-meta-hydroxyephedrine: a false transmitter agent for heart neuronal imaging. J Nucl Med. 1990;31:1328–1334[Abstract/Free Full Text]
15. Brady F, Luthra SK, Tochon-Danguy H, et al. Asymmetric synthesis of a precursor for the automated radiosynthesis of S[11C]CGP 12177 as a preferred radioligand for the beta-adrenergic receptors. Appl Radiat Isot. 1991;42:621–628[Medline]
16. Breithardt G, Cain ME, El-Sherif N, et al. Standards for analysis of ventricular late potentials using high resolution or signal-averaged electrocardiography: a statement by a Task Force Committee between the European Society of Cardiology, the American Heart Association and the American College of Cardiology. Eur Heart J. 1991;12:473–480[Abstract/Free Full Text]
17. Wichter T, Borggrefe M, Haverkamp W, Chen X, Breithardt G. Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease: results in patients with inducible and noninducible ventricular tachycardia. Circulation. 1993;86:29–37
18. Araujo LI, Lammertsma AA, Rhodes CG, et al. Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. Circulation. 1991;83:875–885[Abstract/Free Full Text]
19. Ranicar ASO, Williams CW, Schnorr L, et al. The on-line monitoring of continuously withdrawn blood during PET studies using a single BGO/photomultiplier assembly and non-stick tubing. Med Prog Technol. 1991;17:259–264[Medline]
20. Delforge J, Syrota A, Lançon JP, et al. Cardiac beta-adrenergic receptor density measured in vivo using PET, CGP 12177 and a new graphical method. J Nucl Med. 1991;32:739–748[Abstract/Free Full Text]
21. Choudhury L, Guzzetti S, Lefroy DC, et al. Myocardial beta-adrenoceptors and left ventricular function in hypertrophic cardiomyopathy. Heart. 1996;75:50–54[Abstract/Free Full Text]
22. Lefroy DC, de Silva R, Choudhury L, et al. Diffuse reduction of myocardial beta adrenoceptors in hypertrophic cardiomyopathy: a study with positron emission tomography. J Am Coll Cardiol. 1993;22:1653–1660[Abstract]
23. Lerman BB, Stein K, Engelstein ED, Battleman DS, Lippman N, Bei D, Catanzaro D. Mechanism of repetitive monomorphic ventricular tachycardia. Circulation. 1995;92:421–429[Abstract/Free Full Text]
24. Lerman BB, Stein KM, Markowitz SM. Mechanisms of idiopathic left ventricular tachycardia. J Cardiovasc Electrophysiol. 1997;8:571–583[Medline]
25. Schofer J, Spielmann R, Schuchert A, Weber K, Schlüter M. Iodine-123-meta-iodobenzylguanidine scintigraphy: a noninvasive method to demonstrate myocardial adrenergic nervous system disintegrity in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1988;12:1252–1258[Abstract]
26. Merlet P, Delforge J, Syrota A, et al. Positron emission tomography with 11C CGP-12177 to assess beta-adrenergic receptor concentration in idiopathic dilated cardiomyopathy. Circulation. 1993;87:1169–1178[Abstract/Free Full Text]
27. Gilbert EM, Olsen SL, Renlund DG, Bristow MR. Beta-adrenergic receptor regulation and left ventricular function in idiopathic dilated cardiomyopathy. Am J Cardiol. 1993;71:23–29
28. Böhm M, Gierschik P, Schnabel P, Erdmann E. Myocardial beta-adrenoceptors and inhibitory G-proteins in myocardial biopsies and in explanted hearts from patients with dilated cardiomyopathy. Cardioscience. 1990;1:109–117[Medline]
29. Brodde OE, Zerkowski HR, Doetsch N, Motomura S, Khamssi M, Michel MC. Myocardial beta-adrenoceptor changes in heart failure: concomitant reduction in beta 1- and beta 2-adrenoceptor function related to the degree of heart failure in patients with mitral valve disease. J Am Coll Cardiol. 1989;14:323–331[Abstract]
30. Schäfers M, Dutka D, Rhodes CG, et al. Myocardial presynaptic and postsynaptic autonomic dysfunction in hypertrophic cardiomyopathy. Circ Res. 1998;82:57–62[Abstract/Free Full Text]
31. Goldstein DS, Holmes C, Cannon RO III, Eisenhofer G, Kopin IJ. Sympathetic cardioneuropathy in dysautonomias. N Engl J Med. 1997;336:696–702[CrossRef][Medline]
32. Brush JE, Eisenhofer G, Garty M, et al. Cardiac norepinephrine kinetics in hypertrophic cardiomyopathy. Circulation. 1989;79:836–844[Abstract/Free Full Text]
33. Kiuchi K, Shannon RP, Komamura K, et al. Myocardial beta-adrenergic receptor function during the development of pacing-induced heart failure. J Clin Invest. 1993;91:907–914[Medline]
34. Rimoldi O, Sato N, Uechi M, Shen YT, Pagani M. Role of cardiac and baroreceptor innervation on changing sympatho-vagal balance at baseline and during the development of cardiac heart failure [abstract]. Circulation. 1996;94(Suppl I):I-328
This article has been cited by other articles:
|
|
|
|
 
I. Matsunari, H. Aoki, Y. Nomura, N. Takeda, W.-P. Chen, J. Taki, K. Nakajima, S. G. Nekolla, S. Kinuya, and K. Kajinami
Iodine-123 Metaiodobenzylguanidine Imaging and Carbon-11 Hydroxyephedrine Positron Emission Tomography Compared in Patients With Left Ventricular Dysfunction
Circ Cardiovasc Imaging,
September 1, 2010;
3(5):
595 - 603.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Law, K. Schafers, K. Kopka, S. Wagner, O. Schober, and M. Schafers
Molecular Imaging of Cardiac Sympathetic Innervation by 11C-mHED and PET: From Man to Mouse?
J. Nucl. Med.,
August 1, 2010;
51(8):
1269 - 1276.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sasano, M. R. Abraham, K.-C. Chang, H. Ashikaga, K. J. Mills, D. P. Holt, J. Hilton, S. G. Nekolla, J. Dong, A. C. Lardo, et al.
Abnormal Sympathetic Innervation of Viable Myocardium and the Substrate of Ventricular Tachycardia After Myocardial Infarction
J. Am. Coll. Cardiol.,
June 10, 2008;
51(23):
2266 - 2275.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Kazemi, A. Arya, M. Haghjoo, and M. A Sadr-Ameli
Coincident atrioventricular nodal reentrant and idiopathic ventricular tachycardia.
Asian Cardiovasc Thorac Ann,
August 1, 2006;
14(4):
284 - 288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Dunbar, J. T. Kassotis, E. K. Heyda, B. I. Saul, A. Khan, and J. Gelles
Repetitive Monomorphic Ventricular Tachycardia Associated with Exercise: A Case Report
Angiology,
September 1, 2005;
56(5):
631 - 635.
[Abstract]
[PDF]
|
|
|
|
|
|
|
P. Kies, T. Wichter, M. Schafers, M. Paul, K. P. Schafers, L. Eckardt, L. Stegger, E. Schulze-Bahr, O. Rimoldi, G. Breithardt, et al.
Abnormal Myocardial Presynaptic Norepinephrine Recycling in Patients With Brugada Syndrome
Circulation,
November 9, 2004;
110(19):
3017 - 3022.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Momose, S. Reder, D. M. Raffel, P. Watzlowik, H.-J. Wester, N. Nguyen, P. H. Elsinga, F. M. Bengel, J. Remien, and M. Schwaiger
Evaluation of Cardiac {beta}-Adrenoreceptors in the Isolated Perfused Rat Heart Using (S)-11C-CGP12388
J. Nucl. Med.,
March 1, 2004;
45(3):
471 - 477.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
F.édér. Anselme
Association of idiopathic RVOT VT and AVNRT: anything else than chance?
Europace,
January 1, 2003;
5(3):
221 - 223.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Wichter, M. Schafers, C. G. Rhodes, M. Borggrefe, H. Lerch, A. A. Lammertsma, F. Hermansen, O. Schober, G. Breithardt, and P. G. Camici
Abnormalities of Cardiac Sympathetic Innervation in Arrhythmogenic Right Ventricular Cardiomyopathy : Quantitative Assessment of Presynaptic Norepinephrine Reuptake and Postsynaptic {beta}-Adrenergic Receptor Density With Positron Emission Tomography
Circulation,
April 4, 2000;
101(13):
1552 - 1558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Wichter, P. Matheja, L. Eckardt, P. Kies, K. Schafers, E. Schulze-Bahr, W. Haverkamp, M. Borggrefe, O. Schober, G. Breithardt, et al.
Cardiac Autonomic Dysfunction in Brugada Syndrome
Circulation,
February 12, 2002;
105(6):
702 - 706.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
Top
Abstract
Methods