Changes In Sympathetic Innervation Research Articles

Impact of neonatal hyperoxia on adult cardiac autonomic function in rats: Role of angiotensin II type 1 receptor activation

Individuals born preterm present altered cardiac autonomic function, a risk factor to heart diseases. Neonatal renin-angiotensin-system activation contributes to adult cardiomyopathy in rats exposed to neonatal hyperoxia, a well-established model of preterm birth-related conditions. Central angiotensin II receptor activation is a key modulator of the autonomic drive to the heart. Whether neonatal hyperoxia leads to alteration of the cardiac autonomic function through activation of the angiotensin II receptor type 1 (AT1) is unknown and was examined in the present study.Sprague-Dawley pups were exposed to hyperoxia or room air from postnatal days 3–10. AT1 antagonist losartan or water was given orally postnatal days 8–10. Blood pressure, autonomic function, left ventricular sympathetic innervation, β-adrenergic-receptors expression, and AT1 expression in the solitary-tract-nucleus were examined in adult rats.Neonatal hyperoxia led to loss of day-night blood pressure variation, decreased heart rate variability, increased sympathovagal balance, increased AT1 expression in the solitary-tract, decreased left ventricle sympathetic innervation, and increased β1-adrenergic-receptor protein expression. Losartan prevented the autonomic changes and AT1 expression in the solitary-tract but did not impact the loss of circadian blood pressure variation nor the changes in sympathetic innervation and in β1-adrenergic-receptor expression.In conclusion, neonatal hyperoxia leads to both central autonomic and cardiac sympathetic changes, partly programmed by neonatal activation of the renin-angiotensin system.

Immunohistochemical study of the sympathetic innervation of the colon in chronic slow-transit constipation

The purpose of this study is to determine the distribution and features of sympathetic innervation of the tissues of the human colon wall in chronic slow-transit constipation using immunohistochemical methods. Materials and methods. Immunohistochemical study of large intestine segments (colon and sigmoid colon) obtained as a result of surgical treatment of patients with chronic slow-transit constipation was carried out using neural markers (PGP 9.5 protein, tyrosine hydroxylase, synaptophysin). Results. It has been shown that the majority of postganglionic sympathetic nerve fibers are localized in the Auerbach and Meissner plexuses. Their terminal axons form pericellular synaptic apparatuses around cholinergic neurons. Another part of the sympathetic fibers is involved in the innervation of the muscular plate of the mucous membrane and the walls of the venous vessels of the submucosa; their terminal varicose axons can be seen on smooth muscle cells as distant synapses en passant. Significant features of sympathetic innervation disorders of the large intestine of the studied patients were established; morphological evidence for the reactive, dystrophic and degenerative changes in the sympathetic apparatuses in the ganglionic plexuses were found. The regularities of the absence of sympathetic innervation in two muscle layers (longitudinal and circular), as well as in the mucous membrane, were revealed. Sympathetic neurons were not found in the studied sections of the large intestine. Conclusion. It is assumed that the identified pathological changes in sympathetic innervation in chronic slow-transit constipation can serve as one of the main causes of disruption of normal bowel functions.

Global cardiac sympathetic denervation is associated with diffuse myocardial fibrosis in non-ischemic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Background Occurrence of ventricular tachycardias (VT) has been related to changes in sympathetic innervation and myocardial tissue in ischemic cardiomyopathy. In non-ischemic cardiomyopathy (NICM) patients with VT, the relation between global cardiac sympathetic innervation and non-ischemic fibrosis is less clear. The current gold standard in electrophysiology to identify non-ischemic fibrosis relies on unipolar endocardial voltage mapping. Objective To establish the relationship between global cardiac sympathetic innervation and global fibrosis. Methods 29 patients (93% male, 58 ± 14 years, mean LVEF 38%±13) from the ‘Leiden Nonischemic Cardiomyopathy Study’ undergoing VT ablation between 2011-2018 were included. Endocardial voltage mapping was performed and the mean endocardial unipolar voltage (UV) was taken as a surrogate for global fibrosis. Global cardiac sympathetic innervation was analyzed by 123-I-MIBG imaging using heart-to-mediastinum ratio (HMR). A cut-off of 1.8 was used to delineate between normal (>1.8) and denervated (<1.8). HMR was correlated with mean UV. Results For patients with global cardiac sympathetic denervation a linear relationship was present between HMR and mean UV (R = 0.5278, P = 0.0431. There was no significant linear relationship for patients with normal cardiac sympathetic innervation between HMR and mean UV (R=-0.1696, P = 0.5795). Conclusion Global cardiac sympathetic denervation is related to myocardial fibrosis in patients with NICM and VT. The data support an interplay between denervation and fibrosis which may contribute to arrhythmogeneity, as observed in ICM. Abstract Figure.

The susceptibility of the rat pulmonary and caval vein myocardium to the catecholamine-induced ectopy changes oppositely in postnatal development.

The developmental changes of the caval (SVC) and pulmonary vein (PV) myocardium electrophysiology are traced throughout postnatal ontogenesis. The myocardium in SVC as well as in PV demonstrate age-dependent differences in the ability to maintain resting membrane potential, to manifest automaticity in a form of ectopic action potentials in basal condition and in responses to the adrenergic stimulation. Electrophysiological characteristics of two distinct types of thoracic vein myocardium change in an opposite manner during early postnatal ontogenesis with increased proarrhythmicity of pulmonary and decreased automaticity in caval veins. Predisposition of PV cardiac tissue to proarrhythmycity develops during ontogenesis in time correlation with the establishment of sympathetic innervation of the tissue. The electrophysiological properties of caval vein cardiac tissue shift from a pacemaker-like phenotype to atrial phenotype in accompaniment with sympathetic nerve growth and adrenergic receptor expression changes. The thoracic vein myocardium is considered as a main source for atrial fibrillation initiation due to its high susceptibility to ectopic activity. The mechanism by which and when pulmonary (PV) and superior vena cava (SVC) became proarrhythmic during postnatal ontogenesis is still unknown. In this study, we traced postnatal changes of electrophysiology in a correlation with the sympathetic innervation and adrenergic receptor distribution to reveal developmental differences in proarrhythmicity occurrence in PV and SVC myocardium. A standard microelectrode technique was used to assess the changes in ability to maintain resting membrane potential (RMP), generate spontaneous action potentials (SAP) and adrenergically induced ectopy in multicellular SVC and PV preparations of rats of different postnatal ages. Immunofluorescence imaging was used to trace postnatal changes in sympathetic innervation, β1- and α1A-adrenergic receptor (AR) distribution. We revealed that the ability to generate SAP and susceptibility to adrenergic stimulation changes during postnatal ontogenesis in an opposite manner in PV and SVC myocardium. While SAP occurrence decreases with age in SVC myocardium, it significantly increases in PV cardiac tissue. PV myocardium starts to demonstrate RMP instability and proarrhythmic activity from the 14th day of postnatal life which correlates with the appearance of the sympathetic innervation of the thoracic veins. In addition, postnatal attenuation of SVC myocardium automaticity occurs concomitantly with sympathetic innervation establishment and increase in β1-ARs, but not α1A-AR levels. Our results support the contention that SVC and PV myocardium electrophysiology change during postnatal development, resulting in higher PV proarrhythmicity in adults.

Age-Related Changes in Sympathetic Innervation of the Stomach in Rats

Sympathetic innervation of the stomach is carried out by the prevertebral ganglia of the solar plexus. The localization and neurochemical composition of neurons innervating the stomach in the postnatal ontogenesis of rats have been studied by the method of retrograde axon transport of Fast Blue. In all animals, the celiac ganglia had more labeled neurons than the superior mesenteric ganglion. The number of labeled neurons increased in the first ten days of life and then did not change until senescence. All labeled neurons innervating the stomach contain tyrosine hydroxylase, the catecholamine synthesis enzyme. The proportion of labeled neuropeptide Y-immunopositive neurons did not change during ontogeny; the percentage of labeled calbindin-immunoreactive neurons decreased in the first month of life.

Evaluation of CZT SPECT imaging for cardiac sympathetic innervation in healthy individuals and patients with atrial fibrillation

Background ― Cadmium zinc telluride (CZT) solid-state detectors have been recently introduced in the field of nuclear medicine in cardiology. The aim of the current study was to investigate the scintigraphic patterns of total uptake and the regional distribution of iodine-123 metaiodobenzylguanidine (123I-mIBG) in healthy volunteers and patients with atrial fibrillation (AF) using a gamma camera equipped CZT detectors. Material and Methods ― The total number of included subjects was 30 (15 patients with a paroxysmal form of AF and 15 healthy volunteers). Using a novel single-photon emission computed tomography (SPECT) cardiac dedicated gamma camera equipped CZT-detectors the scintigraphy was performed 15 minutes and 4 hours after intravenous administration of norepinephrine structural analogue 123I-mIBG. Thus, data from early and delayed phases were obtained. The heart-to-mediastinum ratio of 123I-mIBG uptake at 15 minutes (HMRe) and 4 hours (HMRd), as well as the washout rate (WR) and summed 123I-mIBG score (SMSe, SMSd) were measured. Results ― Patients and volunteers showed comparable results of the median ratio of 123I-mIBG uptake in the heart and mediastinum (HMR) in the early and delayed phases (p>0.05). In 14 (93%) patients with AF, 123I-mIBG uptake defects in LV myocardium were detected as compared with 8 (53%) healthy individuals (p<0.05). The healthy volunteers showed no significant 123I-mIBG uptake defect in delayed scans compared with a median result in patients with AF (p<0.001). Conclusion ― SPECT gamma camera with CZT-detectors is suitable to obtain qualitative tomographic slices of the myocardium and to assess regional changes in sympathetic innervation of the heart, which can be the early signs of an imbalance in the autonomic nervous system. Therefore, this camera may be useful for managing patients with various forms of AF.

“Brain over body”–A study on the willful regulation of autonomic function during cold exposure

The defense of body temperature against environmental thermal challenges is a core objective of homeostatic regulation governed by the autonomic nervous system. Autonomous mechanisms of thermoregulation are only weakly affected by top-down modulation, allowing only transient tolerance for extreme cold. There is however, anecdotal evidence of a unique set of individuals known for extreme cold tolerance. Here we present a case study of a 57-year old Dutch national, Wim Hof, the so-called “Iceman”, with the ability to withstand frequent prolonged periods of extreme cold exposure based on the practice of a self-developed technique involving a combination of forced breathing, cold exposure and meditation (collectively referred to as the Wim Hof Method, henceforth “WHM”). The relative contributions of the brain and the periphery that endow the Iceman with these capabilities is unknown. To investigate this, we conducted multi-modal imaging assessments of the brain and the periphery using a combination of fMRI and PET/CT imaging. Thermoregulatory defense was evoked by subjecting the Iceman (and a cohort of typical controls) to a fMRI paradigm designed to generate periods of mild hypothermia interspersed by periods of return to basal core body temperature. fMRI was acquired in two separate sessions: in a typical (passive) state and following the practice of WHM. In addition, the Iceman also underwent a whole body PET/CT imaging session using the tracers C11-hydroxyephedrine (HED) and 18F-fluorodeoxyglucose (FDG) during both thermoneutral and prolonged mild cold conditions. This acquisition allowed us to determine changes in sympathetic innervation (HED) and glucose consumption (FDG) in muscle and fat tissues in the absence of the WHM. fMRI analyses indicated that the WHM activates primary control centers for descending pain/cold stimuli modulation in the periaqueductal gray (PAG), possibly initiating a stress-induced analgesic response. In addition, the WHM also engages higher-order cortical areas (left anterior and right middle insula) that are uniquely associated with self-reflection, and which facilitate both internal focus and sustained attention in the presence of averse (e.g. cold) external stimuli. However, the activation of brown adipose tissue (BAT) was unremarkable. Finally, forceful respiration results in increased sympathetic innervation and glucose consumption in intercostal muscle, generating heat that dissipates to lung tissue and warms circulating blood in the pulmonary capillaries. Our results provide compelling evidence for the primacy of the brain (CNS) rather than the body (peripheral mechanisms) in mediating the Iceman's responses to cold exposure. They also suggest the compelling possibility that the WHM might allow practitioners to develop higher level of control over key components of the autonomous system, with implications for lifestyle interventions that might ameliorate multiple clinical syndromes.

Changes in Sympathetic Innervation of the Heart in Rats with Experimental Myocardial Infarction. Effect of Semax.

The effect of peptide Semax on remodeling of cardiac sympathetic innervation was examined in rats with experimental myocardial infarction. In 28 days after ischemia/reperfusion injury, Semax diminished the growth of sympathetic innervation of ventricular septum, although it produced no effect on the density of β1 and β2 adrenoceptors.

Neonatal testosterone exposure induces early development of follicular cysts followed by sympathetic ovarian hyperinnervation.

This study analysed the temporal association between ovarian cyst development induced by neonatal androgenisation and sympathetic innervation. Neonatal rats (postnatal Days 1 to 5) were treated with testosterone or dihydrotestosterone and the effects were evaluated at postnatal Days 20, 40, 90 or 180. Ovulation rate, number of cystic follicles and density of sympathetic fibres were analysed. The effects of surgical denervation or gonadotrophin stimulation were also assessed. Rats exposed to testosterone showed no oestrous cycle activity and did not ovulate, maintaining a polycystic ovarian morphology at all ages studied. Also, a significant increase in ovarian density of noradrenergic fibres was detected at postnatal Days 90 and 180. Sympathectomy was unable to re-establish ovarian activity; however, human chorionic gonadotrophin stimulation was enough to induce ovulation. The impact of dihydrotestosterone on ovarian function was less noticeable, showing the coexistence of corpora lutea and cystic structures without changes in sympathetic innervation. Our findings suggest that a remodelling of ovarian sympathetic innervation occurs as a response to modifications in the pattern of follicular growth induced by testosterone. A role of sympathetic innervation in the maintenance of the polycystic condition is suggested.

Effect of Pregnancy on Autoregulation of Cerebral Blood Flow in Anterior Versus Posterior Cerebrum

Severe preeclampsia and eclampsia are associated with brain edema that forms preferentially in the posterior cerebral cortex possibly because of decreased sympathetic innervation of posterior cerebral arteries and less effective autoregulation during acute hypertension. In the present study, we examined the effect of pregnancy on the effectiveness of cerebral blood flow autoregulation using laser Doppler flowmetry and edema formation by wet:dry weight in acute hypertension induced by phenylephrine infusion in the anterior and posterior cerebrum from nonpregnant (n=8) and late-pregnant (n=6) Sprague-Dawley rats. In addition, we compared the effect of pregnancy on sympathetic innervation by tyrosine hydroxylase staining of posterior and middle cerebral arteries (n=5-6 per group) and endothelial and neuronal NO synthase expression using quantitative PCR (n=3 per group). In nonpregnant animals, there was no difference in autoregulation between the anterior and posterior cerebrum. However, in late-pregnant animals, the threshold of cerebral blood flow autoregulation was shifted to lower pressures in the posterior cerebrum, which was associated with increased neuronal NO synthase expression in the posterior cerebral cortex versus anterior. Compared with the nonpregnant state, pregnancy increased the threshold of autoregulation in both brain regions that was related to decreased expression of endothelial NO synthase. Lastly, acute hypertension during pregnancy caused greater edema formation in both brain cortices that was not attributed to changes in sympathetic innervation. These findings suggest that, although pregnancy shifted the cerebral blood flow autoregulatory curve to higher pressures in both the anterior and posterior cortices, it did not protect from edema during acute hypertension.

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat

The noradrenaline (NA) concentration in the rat corpus cavernosum (CC) increased to approximately 350% of control values after about 8 weeks of hyperglycaemia induced by the intraperitoneal injection of streptozotocin (STZ) at 10 weeks of age. These changes were maintained for at least a further 32 weeks of hyperglycaemia and occurred without any significant change in the weight in the tissue. Smaller but significant increases in NA concentration occurred in the glans penis (GP) reaching 150-175% of the control levels during the period of prolonged hyperglycaemia. In contrast, there was no significant change in the NA concentration in the penile urethra. Measurements have also been made that relate to changes in the synthesis and reuptake of NA in the CC during the period during which high NA concentration is maintained. Immunohistochemical studies for the synthetic enzyme tyrosine hydroxylase in the CC indicate that the intensity of staining in the tissue had increased after 10, 20 and 32 weeks of hyperglycaemia, relative to the tissues from control animals. Dilated nerve fibres and engorged endings were present in the CC of the diabetic animals at these times. Reuptake of tritiated NA by the terminal axonal membranes in the CC was raised to 181% of control values after 12 weeks of hyperglycaemia (P<0.05), but later declined to values that are not significantly different from the control levels (after 26 and 64 weeks of hyperglycaemia). There are few studies of the effects of prolonged diabetes on functional aspects of sympathetic postganglionic neurones in the CC, and this paper suggests that the changes described represent remodelling of noradrenergic axonal terminals starting about after 8-10 weeks of hyperglycaemia; this delay in onset of the neuropathic changes is also a feature of type I diabetes in humans.

Dexamethasone-induced Changes in Sympathetic Innervation of Porcine Ovaries and in Their Steroidogenic Activity

The aim of the present study was to determine changes in the density of sympathetic nerves in porcine ovaries with dexamethasone (DXM)-induced cysts and the alterations in steroidogenic activity and amounts of catecholamines in the affected gonads. Cystic ovaries were supplied by numerous sympathetic nerve fibers. The amount of noradrenaline in the cysts (fluid, wall) was significantly higher than in the large follicles of the control group. After DXM injections, the amounts of noradrenaline and adrenaline significantly increased in the walls of small and medium-sized follicles. In the cysts (fluid, wall) the levels of androgens and estrogens were significantly lower, whereas progesterone was higher in the cystic wall. DXM administration led to a significant increase in the estrone content in the fluid of small follicles. Moreover, a decrease in the amounts of progesterone and androgens was found in the follicular fluid and walls of medium-sized follicles. DXM injections resulted in a significant increase in the immunoexpression of P450(scc) and 3beta-HSD in the cysts, a significant increase of P450(scc) in the follicles, and a decrease of 3beta-HSD and P450(arom). The present study shows that the DXM treatment leads to an increase in the density of intraovarian sympathetic nerves, paralleled by the amount of catecholamines, and that it is capable of changing the steroidogenic activity of porcine ovary bearing cysts. Thus, it appears possible that these events may be, at least partly, involved in the pathogenesis of this disorder.

Sympathetic Innervation of the Tongue in Rats

We employed a glyoxylic catecholaminergic histofluorescence method to study the sympathetic innervation present in the rat tongue. One percent neutral red was used as a counterstain. Many noradrenergic fibers were demonstrated around the blood vessels, muscles, glands and submucosa of the tongue, but not in the epithelium or papilla. In a group of rats following neurectomy, the superior cervical ganglia (SCG) were removed unilaterally or bilaterally. Changes in sympathetic innervation of the tongue were examined 14 days after SCG ganglionectomy. In those animals after unilateral SCG ganglionectomy, we found no noradrenergic histofluorescence in the ipsilateral anterior 2/3 of the tongue, although some scant fluorescence was found in the ipsilateral posterior 1/3 of the tongue. However, no noradrenergic histofluorescence could be observed in animal’s bilateral SCG ganglionectomies. Our results indicate that sympathetic innervation of the tongue in rats originates in the SCG, with some cross-innervation of the sympathetic fibers occurring in the posterior 1/3 of the tongue.

Age-Related Changes in Noradrenergic Sympathetic Innervation of the Rat Spleen Is Strain Dependent

Previous findings from our laboratory revealed an age-related decline in noradrenergic (NA) sympathetic innervation of the spleen in male Fischer 344 (F344) rats. The purpose of this study was to determine whether other rat strains also progressively lose NA sympathetic nerves in the aging spleen. Sympathetic innervation of spleens from 3- and 21-month-old male F344, Brown Norway (BN), BN X F344 (BNF1), and Lewis rats was examined using fluorescence histochemistry to localize catecholamines combined with morphometric analysis and using high-performance liquid chromatography with electrochemical detection for measuring norepinephrine (NE). Neurochemistry revealed a significant age-related decline in NE concentrations in spleens from F344 and Lewis rats. In contrast, there was no effect of age on splenic NE concentrations in BN or BNF1 rats. Consistent with neurochemical analysis, fluorescence histochemistry revealed a striking decline in NA innervation of spleens from old F344 and Lewis rats not observed in the other two strains. However, in BN and BNF1 rats, nerve fibers were diminished in distal portions of the spleen but not in the hilar regions. Morphometric analysis confirmed neurochemical and histological findings, revealing approximately 65–70% loss in NA nerve density in spleens from F344 and Lewis rats. These findings indicate that age-related changes in sympathetic innervation of the rat spleen are strain-dependent. Whether the loss of sympathetic nerves in spleens from F344 and Lewis rats is associated with age-related changes in the splenic microenvironment remains to be determined. The functional significance of altered sympathetic innevation of the spleen with advancing age is discussed.

Postnatal Development of Peptidergic Innervation of the Canine Heart

The autonomic innervation of the canine heart develops with considerable regional asymmetry during the early neonatal period. To examine the development of the peptidergic component of the innervation, 28 mongrel puppies 1–6 weeks of age from five litters were studied at weekly intervals. Four of the mothers were also studied as adult and breed controls. Tissue neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) concentrations were determined by radioimmunoassay in myocardial specimens obtained from several specific sites of the cardiac chambers and from the proximal coronary arteries. Data were analysed according to age, cardiac chamber/vessel, gender and individual litter. In general, NPY concentrations in pg/mg protein were six- to eight-fold higher than those of VIP. Also concentrations for both peptides were about two-fold higher in the coronary arteries than the myocardium and differed among chambers, being higher and similar in the atria and lower in the ventricles, particularly for NPY. No gender differences were identified. Concentrations varied among litters, but the developmental pattern was similar with the highest peptide concentrations identified in the first and fourth week. Whereas the differences among chambers may also reflect differing rates of developmental increase of myocardial mass, the pattern corresponds only in part to previously identified functional changes in sympathetic innervation since, in contrast to previous findings, high NPY concentrations in the first 2 weeks suggest anatomically advanced innervation.

Free plasma catecholamines in spinal cord injured persons with different injury levels at rest and during exercise

Spinal cord lesion leads to an interruption of pathways from brain to the peripheral sympathetic nervous system, which results in pathological changes in sympathetic innervation. Free epinephrine (E), norepinephrine (NE) and dopamine (DA) were measured in 30 tetraplegics (TETRA), 15 high-lesion paraplegics (T 1 and T 4, HPARA), 15 paraplegics with injuries between T 5 and T 10 (MPARA), 15 low-lesion paraplegics (below T 10, LPARA) and 16 non-handicapped control persons (C) at rest, at 60 and 100% of maximal oxygen consumption during graded wheelchair ergometry (WCE). The TETRA showed significant lower E and NE levels at rest and only slight increases during physical exercise. The E and NE concentrations of the paraplegics with a lesion below T 5 were significantly higher than those of the high-lesion paraplegics, as well as those of the control persons at every point in the study. All paraplegics and the control persons showed, at submaximal and maximal exercise, a significant increase in NE. Only a slight increase in E in HAPRA was shown. No differences were found at rest and during exercise in E and NE levels in the MPARA and LPARA. No significant differences were found in the dopamine concentration at rest or during exercise for any of the groups. In summary, different levels of lesion and the resulting interruption to sympathetic pathways in the spinal cord are decisive factors in the degree of impairment of sympathetic innervation in SCI persons. Tetraplegics show less preganglionic resting activity because of interruption of impulses from central centers and no considerable stimulation of the sympathetic nervous system during maximal exercise. Individuals with high paraplegia have a partial impairment of catecholamine release, especially of epinephrine, at rest and during exercise. Paraplegics with a lesion level below T 5 showed an augmented basal and exercise-induced upper spinal thoracic sympathetic activity in comparison to control persons.

Does radiofrequency catheter ablation induce a deterioration in sympathetic innervation? A positron emission tomography study.

Radiofrequency catheter ablation (RFCA) is an effective treatment for the interruption of accessory bypass tracts in WPW syndrome or the modification of the AV-nodal conduction system in patients with AV-nodal tachycardias. However RFCA may also damage cardiac innervation. The purpose of this pilot study was to assess possible changes in sympathetic innervation after RFCA as evaluated by the cathecholamine analog carbon-11-hydoxyephedrine (HED) positron emission tomography (PET) which allows the visualisation of sympathetic nerve terminals. We investigated nine patients with supraventricular tachycardias before and two to six weeks after RFCA. Myocardial perfusion was depicted by n-13-ammonia-PET. In addition to visual analysis, HED retention was quantified in the myocardial quadrant distal to the location of intervention; these results were compared with values in remote areas. Before RFCA, myocardial perfusion showed homogenous distribution in 8 of 9 patients. One patient showed a perfusion defect in the posterior wall. HED retention matched perfusion distribution in all patients. After RFCA there was no significant change observed either in ammonia or in HED distribution. Quantitative HED retention data showed no significant change before versus after RFCA. Thus, HED-PET does not demonstrate any abnormalities of tracer uptake indicating integrity of sympathetic nerve terminals after radiofrequency ablation therapy.

Sympathetic innervation of the eustachian tube in rats.

The glyoxylic catecholaminergic histofluorescence method was employed on the mucosa of the rat's eustachian tube (ET) in order to study the sympathetic innervation present. One percent neutral red was used as counterstain. Many noradrenergic fibers were demonstrable around blood vessels, glands and submucosa of the ET, but not in the epithelium. In a group of rats following neurectomy, the superior cervical ganglia (SCG) were removed unilaterally or bilaterally. Changes in sympathetic innervation of the ET were examined 14 days after SCG ganglionectomy. In those animals after unilateral SCG ganglionectomy, no noradrenergic histofluorescence was found in the ipsilateral ET, although some scant fluorescence could be detected in the tube's nasopharyngeal (NP) orifice. However, no noradrenergic histofluorescence could be observed in animals bilateral SCG ganglionectomies. Our results indicate that sympathetic innervation of the ET in the rat originates in the SCG, with some cross-innervation of sympathetic fibers occurring in the tube's NP orifice.

Quantitative analysis of 123I-metaiodobenzylguanidine (MIBG) uptake in hypertrophic cardiomyopathy

Myocardial scintigraphy with 123I-meta-iodobenzylguanidine (MIBG) and thallium-201 (201Tl) was performed in 29 patients with hypertrophic cardiomyopathy (HCM) using whole-body scintigraphy and single-photon emission computed tomography (SPECT). Nonhypertensive patients were classified into three groups according to the septal thickness determined by ultrasonography; group 1 (wall thickness less than 16 mm, n = 5), group 2 (from 16 to 20 mm, n = 12) and group 3 (greater than 20 mm, n = 4). The regional myocardial uptakes of both 201Tl and 123I-MIBG (percent of injected dose/cm3 myocardium) were higher in the more hypertrophic septa. However, when regional MIBG uptake at 3 hours was divided by the 201Tl uptake to calculate the MIBG uptake per unit of blood flow, the hypertrophic septa showed lower mean values--0.39 +/- 0.23 and 0.50 +/- 0.10 in groups 3 and 2, respectively (p less than 0.1 compared with 0.69 +/- 0.20 in group 1). The regional MIBG clearance rate in the septum was significantly higher in group 3 compared with group 1 (13.4 +/- 8.0%/hr versus 1.5 +/- 6.2%/hr, p less than 0.05). The uptake and 123I-MIBG clearance rate in the lateral wall showed a similar tendency. Myocardial uptake determined by whole-body scintigraphy was slightly increased in group 2 (3.5 +/- 0.6%, p less than 0.05) compared with group 1 (2.7 +/- 0.8%); however, it was lower in group 3 (2.7 +/- 0.4%). Myocardial 123I-MIBG distribution demonstrated various patterns in comparison with 201Tl distribution, suggesting that flow-independent changes in sympathetic innervation or activity may exist in patients with HCM.(ABSTRACT TRUNCATED AT 250 WORDS)

Presynaptic and postsynaptic alpha 2-adrenergic receptors in human cerebral arteries and their alteration after subarachnoid hemorrhage.

The nature of alpha-adrenergic receptors in human cerebral arteries was characterized, and alteration of these receptors after subarachnoid hemorrhage was examined using a radioligand binding assay. Norepinephrine content of control arteries was also analyzed and compared with that of arteries after subarachnoid hemorrhage. Norepinephrine content in human cerebral arteries in cases of subarachnoid hemorrhage was about 5% of the control group. Specific binding of [3H]yohimbine, a selective alpha 2-antagonist, to cerebral arteries of the control group indicated two classes of binding sites: high-affinity sites with KD of 0.5 nM and Bmax of 18 fmol/mg protein and low-affinity sites with KD of 29 nM and Bmax of 248 fmol/mg protein. In cerebral arteries obtained from the subarachnoid hemorrhage group, [3H]yohimbine binding sites were of a single class with KD of 53 nM and Bmax of 456 fmol/mg protein. These results suggest that sympathetic denervation and subsequent alterations in alpha 2-adrenergic receptors occurred after subarachnoid hemorrhage in human cerebral arteries. These changes in sympathetic innervation to cerebral arteries were considered to be one of the antecedents of delayed vasospasm after subarachnoid hemorrhage.