Iodine 123-metaiodobenzylguanidine imaging reflect generalized sympathetic activation in patients with left ventricular dysfunction

BACKGROUND: Iodine 123-metaiodobenzylguanidine (MIBG) imaging has been used to assess cardiac sympathetic nerve abnormalities. To determine the role of MIBG imaging as a measure of generalized sympathetic nerve activity, MIBG imaging was evaluated with muscle sympathetic nerve activity (MSNA) and plasma norepinephrine (noradrenaline) level in patients with old myocardial infarction. METHODS: Myocardial MIBG scintigraphy, MSNA and plasma norepinephrine measurement were performed within 3 days in 35 patients with old myocardial infarction. Patients were divided into three groups according to their ejection fraction (EF); preserved (EF > or = 50%, 12 patients), intermediate (35% < EF < 50%, 13 patients), or depressed (EF < or = 35%, 10 patients).The heart to mediastinum (H/M) ratio was obtained 4 h after tracer injection from the chest anterior view image. MIBG washout rate was calculated from the early and delayed images. MSNA was recorded by microneurography. RESULTS: Plasma norepinephrine level had weak negative correlations with early H/M ratio (r = 0.37, P<0.05) and delayed H/M ratio (r = 0.33, P<0.05), and a positive correlation with MIBG washout rate (r = 0.54, P<0.01). MSNA had weak negative correlations with early H/M ratio (r = 0.51, P<0.05) and delayed H/M ratio (r = 0.52, P<0.05). However, a strong correlation was found between MSNA and MIBG washout rate (r = 0.88, P<0.001). Despite no significant differences in plasma norepinephrine level and H/M ratio, patients with intermediate and depressed EF had higher MIBG washout rate and MSNA compared with those with preserved EF. CONCLUSIONS: Increased in cardiac sympathetic nerve activity was associated with augmented sympathetic outflow of the skeletal muscle and hence, MIBG washout rate allow the assessment of general sympathetic nerve activity.     

长期压力超负荷大鼠心脏交感神经NET、NGF及其受体表达变化

目的 检测长期心脏压力超负荷(pressure overload,POL)大鼠心脏交感神经去甲肾上腺素转运蛋白(norepinephrine transporter NET)、心肌神经生长因子(nerve growth factor NGF)及受体TrkA表达变化,探讨心脏压力超负荷导致交感神经重塑的机制.方法 40只雄性Wistar大鼠分为假手术对照组(n=10)和POL组(n=30).建立腹主动脉缩窄大鼠心脏POL模型,术后8周,用超声心动图评价大鼠心脏功能,用免疫组化荧光方法检测左心室心肌NGF蛋白表达,实时荧光定量PCR检测心脏交感神经节NET及左室心肌GAP43(growth associated factor,GAP43)、TrkA mRNA表达变化.结果 与假手术组比较,POL大鼠心室间隔舒张期厚度(interventricularseptal thickness during diastole,IVSd)、收缩期心室间隔厚度(interventricularseptal thickness during systole,LVSs)、舒张期左室后壁厚度(diastolic LV posterior wall thickness,LVPWd)显著增厚,左室质量指数(left ventricular mass index,LVMI)升高33.23％(P＜0.05);心功能(EF、FS％)增强(P＜0.05),表明大鼠心功能代偿.POL组心肌NGF蛋白表达增加(P＜0.05),但心肌GAP43、心脏NET mRNA水平未见变化(P＞0.05),TrkA mRNA表达下降(P＜0.05).结论 POL后心肌TrkA mRNA低表达可能是限制心肌NGF蛋白促交感神经生长的原因,心脏NET mRNA转录后异常或内化可能是POL后NET功能异常原因.     

Types of Adrenoreceptors Mediating Responses of Rabbit Gastric Muscularis Mucosae

This study investigated adrenoreceptor-mediated responses of muscularis mucosae from the fundic and antral ends of the rabbit gastric corpus. Norepinephrine-induced fundic muscularis mucosae contractions were enhanced by propranolol and converted to relaxations by phentolamine. Methoxamine, but not clonidine, elicited large fundic contractions. Fundic muscle responded to low isoproterenol concentrations with atenolol- and butoxamine-resistant relaxations, and to high concentrations with atenolol-sensitive contractions. Norepinephrine evoked propranolol-resistant relaxations of antral muscularis mucosae that were enhanced by phentolamine. Methoxamine and clonidine elicited small antral contractions. Lower concentrations of isoproterenol caused atenolol-resistant antral relaxations that were enhanced by butoxamine; higher concentrations produced weak excitation. Fundic and antral relaxations to isoproterenol were abolished by cyanopindolol. Fundic muscularis mucosae possesses excitatory ₁-, ₁- and inhibitory ₃-adrenoreceptors. Excitatory ₂- and inhibitory ₃-adrenoreceptors predominate in the antral region. The heterogeneous adrenoreceptor-mediated responses of the gastric muscularis mucosae suggest that adrenergic modulation of its motor activity is unlikely to be linked to acid secretion.     

Catecholamine concentrations in biopsied gastroduodenal tissue specimens of patients with duodenal ulcer

We measured dopamine and norepinephrine concentrations in the biopsied gastroduodenal mucosa obtained from 12 ulcer-free dyspeptic patients, nine patients with active duodenal ulcer, and eight patients with inactive (or healed) duodenal ulcer using a high-performance liquid chromatography with electrochemical detection method. Biopsy specimens were taken from endoscopically normal-appearing mucosa in the gastric body and antrum as well as in the duodenal bulb. Additional specimens were obtained from the outer edge of the ulcer margin in patients with active duodenal ulcer. The mean (±SD) mucosal dopamine concentrations in the gastric body and duodenum (7.6±2.8 and 6.8±2.6 pg/mg tissue) obtained from patients with inactive duodenal ulcer were significantly (P<0.05) lower than those from dyspeptic patients (13.6±6.9 and 10.9±3.5 pg/mg tissue, respectively). In contrast, no significant differences were observed in the mean norepinephrine concentrations in these gastroduodenal tissues among the three study groups. However, the mean mucosal norepinephrine concentration in the outer edge of duodenal ulcer (86.2±125.6 pg/mg tissue) was significantly (P<0.05 and 0.01) reduced as compared with that in the ulcer-free area of duodenum obtained from patients with inactive duodenal ulcer (257.1±188.2 pg/mg tissue) and from dyspeptic patients (276.8±138.3 pg/mg tissue). The results suggest that an alteration in the catecholaminergic system may be associated with one of the pathogenic factors of duodenal ulcer.This study was supported by a grant-in-aid from the Ministry of Human Health and Welfare, Tokyo.     

Influence of ageing on the sympathetic nervous system and adrenal medulla at rest and during stress

The influence of ageing on the sympathetic nervous system and adrenal medulla was studied neuro chemically in humans, using isotopic dilution measurement of regional and whole body catecholamine release to plasma in humans. With ageing, sympathetic activation was evident in the heart, and the gut and liver at rest. The mechanism appeared to be by activation of sympathoexcitatory noradrenergic suprabulbar projections from the brainstem. Sympathetic nervous responses with stressors were augmented. Conversely, adrenal medullary release of epinephrine was subnormal in the elderly, at rest and during stress. This revised version was published online in July 2006 with corrections to the Cover Date.     

Pathophysiologic significance of left ventricular hypertrophy in dilated cardiomyopathy

Background and hypothesis: Patients with dilated cardiomyopathy (DCM) with left ventricular hypertrophy (LVH) have been found to have a better prognosis than patients without LVH. However, the pathophysiologic mechanism for that has not been investigated. We sought to clarify the pathophysiologic significance of LVH in DCM. Methods: We performed isoproterenol infusion echocar-diography (0.02 m?g/kg/min) in 17 patients with DCM, and measured plasma epinephrine and norepinephrine levels at rest and at the end of ergometer exercise in 14 of the 17 patients. Patients were classified into groups according to the presence (9 patients) (LVH+) or absence (8 patients) (LVH-) of LVH. Left ventricular hypertrophy was defined as an inter-ventricular thickness or posterior wall thickness ≥13 mm. Results: Although there was no significant difference between groups in fractional shortening at rest during isoproterenol infusion, fractional shortening was significantly higher in the LVH (+) group than in the LVH (-) group (29 ± 9 vs. 17 ± 8%;p<0.025). Although there was no significant difference in plasma norepinephrine level, it was significantly lower in the LVH (+) group than in the LVH (-) group (233 ± 169 vs. 519 ± 258 pg/ml;p<0.05) at the end point of the exercise. Conclusion: Systolic reserve, represented by the response to isoproterenol, is greater in patients with DCM with LVH than in those without LVH, and a lower plasma level of norepinephrine is needed to activate the myocardium during ex ercise in patients with DCM with LVH. This pathophysiologic characteristic could be one of the mechanisms which explain a better prognosis in patients with DCM with LVH.