Comparison of plasma 3,4-dihydroxyphenylethylene glycol (DHPG) and norepinephrine levels as indices of sympathetic activity in man

Plasma levels of norepinephrine (NE) and the NE metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) were measured simultaneously following sympathetic activation induced by standing, cold pressor testing and bicycle exercise at progressively increasing workloads in normal volunteers. Free DHPG and NE levels both increased with sympathetic activation, but free NE levels were a more sensitive index of change. In addition, plasma free NE levels more closely reflected the fall in heart rate following exercise than free DHPG. In contrast to free levels, conjugated DHPG and NE levels did not change significantly after exercise. Supine resting free DHPG/NE ratios were always greater than 2.0, but fell progressively with increasing sympathetic activation because of a proportionately greater rise in NE than DHPG. The simultaneous measurement of plasma free DHPG and NE does not offer advantages over free NE levels as an index of sympathetic activity in man, but may be of use in the diagnosis of pheochromocytoma and in studies of NE metabolism.     

Increase in plasma 3,4-dihydroxyphenylalanine (DOPA) appearance rate after inhibition of DOPA decarboxylase in humans

Abstract. Concentrations of DOPA in plasma are relatively high as compared to norepinephrine. The significance of plasma DOPA has not been elucidated. One would expect that substantial amounts of DOPA are derived from sympathetic nerves. There appears, however, neither to be a depot of DOPA in nerves nor is there a close correlation between plasma DOPA and sympathetic activity. The aim of the present study was to obtain further information about plasma DOPA by studying DOPA kinetics in healthy humans both with and without inhibition of DOPA decarboxylase by benserazide. Plasma DOPA and other catecholamines were measured by reverse-phase HPLC with electrochemical detection and DOPA clearance and appearance rate were studied using infusion of ³H-DOPA. The plasma clearance of DOPA was 1·02 1 min^-1. Approximately 20% of this value could be explained by DOPA being decarboxylated in the kidneys and excreted as dopamine. The DOPA appearance rate was 1·13 μg min^-1 and the extremities accounted for approximately 1/5 of this value. After inhibition of DOPA decarboxylase by benserazide the DOPA appearance rate increased 7-fold, whereas the DOPA clearance only decreased slightly and insignificantly. These findings are probably explained by two factors: (1) There is normally a large production of DOPA in some tissues from which DOPA spillover into plasma only occurs to a minor extent and tracer DOPA only mixes with this compartment to a small degree; (2) These compartments are permeable to benserazide, which blocks the decarboxylation of DOPA, which then leaves the tissues and spillover to plasma. Our results are compatible with the view that substantial amounts of DOPA are normally decarboxylated in sympathetic nerves, and spillover to plasma only if DOPA cannot be decarboxylated to dopamine. We conclude that plasma DOPA concentration neither reflects sympathetic nerve activity nor tyrosine hydroxylase activity. Provided plasma DOPA to a major extent is derived from sympathetic nerves it probably reflects the minimal fraction of DOPA synthesized but not decarboxylated to dopamine in nerves.     

Muscle nerve sympathetic activity in migraine. Lack of abnormality

Microelectrode recordings of muscle nerve sympathetic activity (MSA) in the peroneal nerve were performed in eight patients with common migraine, when they were free of headache and during a spontaneously occurring attack of migraine. During the migraine headache all subjects remained on the same level of MSA as in the control situation and the responses to manoeuvres (slow deep breathing, the Valsalva manoeuvre, sustained hand grip, immersion of one hand into ice water) showed no qualitative or quantitative change. Assessment of vagal influence on the heart showed no change from control situation to attack of migraine. The study provides direct evidence against the existence of any abnormality of MSA during ongoing migraine headache and does not support the assumption that migraine is a generalized vasomotor disorder. No conclusions about possible dysfunction in other parts of the sympathetic nervous system can be drawn.     

Plasma dihydroxyphenylglycol (DHPG) as an index of diabetic autonomic neuropathy

Summary. Forearm venous plasma noradrenalin and dihydroxyphenylglycol (DHPG) concentrations were measured in eight diabetic patients with and eight diabetic patients without neuropathy. Plasma noradrenalin was on average the same in patients with and without neuropathy and correlated to serum creatinine. Plasma DHPG concentrations were significantly reduced in patients with autonomic neuropathy as compared to patients without neuropathy (P<0·05). A low plasma DHPG/noradrenalin ratio in forearm venous blood identified all patients with autonomic neuropathy except one (P<0·02). Measuring the plasma DHPG/noradrenalin ratio may circumvent the problem of unrepresentative noradrenalin release from the forearm.     

The effects of clonidine on arterial baroreflex sensitivity and cardiopulmonary baroreflex control of sympathetic nerve activity in patients with left ventricular dysfunction

Background: Clonidine is a potent sympatholytic drug with central neural effects. The aim of this study was to evaluate the effects of clonidine on arterial baroreflex sensitivity (BRS) and cardiopulmonary (CP) baroreflex control of muscle sympathetic nerve activity (MSNA) in patients with left ventricular (LV) dysfunction. Method: Twenty patients were randomly assigned to either clonidine or placebo groups (10 in each group). BRS (by phenylephrine method) and CP baroreflex (by lower body negative pressure) effects on sympathetic nerve activity (circulating norepinephrine and MSNA recordings) were measured before and after a 4‐week treatment period. Results: Clonidine lowered blood pressure and heart rate. Clonidine was accompanied not only by a decrease in plasma noradrenaline (from 444 ± 196 to 260 ± 144 pg ml^?1) but also by a reduction in directly measured MSNA (from 47 ± 16 to 36 ± 16 bursts min^?1). BRS increased significantly from 3·01 ± 1·19 to 6·86 ± 2·84 ms mmHg^?1 after clonidine. When expressed as per cent change in MSNA during CP baroreceptor stimulation, CP baroreflex control of MSNA was significantly increased from 9·26 ± 8·93% to 28·83 ± 11·96% after clonidine. However, there were no significant changes in the measured variables in the control group. Conclusion: Clonidine enhanced BRS and CP baroreflex control of MSNA while reducing baseline sympathetic activity in patients with LV dysfunction.     

Response of sympathetic nervous system activity to exercise in patients with congestive heart failure

To investigate the serial sympathetic nervous system response to exercise, plasma norepinephrine (NE) and epinephrine (E) concentrations were measured at rest, during each stage of treadmill exercise, and immediately and 5 minutes after exercise in 68 congestive heart failure (CHF) patients (NYHA functional class I 24, II 25, III 19) and 30 normal subjects. Circulatory responses of NYHA class II patients increased at early stages of exercise. Systolic blood pressure and double product at peak exercise were significantly lower in NYHA class III patients. Plasma NE response of NYHA class I patients was similar to that of normal subjects. However, plasma NE at rest, and during and after exercise were significantly higher in NYHA classes II and III patients than in normal subjects and NYHA class I patients (peak NE (pg ml-1); Normals: 547 +/- 37, I: 535 +/- 53, II: 867 +/- 87, III: 1033 +/- 157). There was no significant difference in plasma E levels among the four groups. NE response to exercise was augmented according to the severity of heart failure, which suggested compensatory activation of sympathetic nervous system activity. Circulatory responses were reduced in NYHA class III patients despite the exaggerated compensatory activation of the sympathetic nervous system. Blunted circulatory responses to increased NE concentration in NYHA class III patients might relate to a decreased cardiac responsiveness to sympathetic activity in severe CHF patients.     

2型糖尿病患者交感神经皮肤反应检测及中医证候研究

目的研究交感神经皮肤反应（SSR）在2型糖尿病（T2DM）周围神经病变中的诊断价值，分析其与中医证候之间的关系。方法检测192例T2DM患者的SSR；按气虚、阴虚、阳虚、血瘀、痰湿进行中医证候归类，用5级记分法进行量化评分。结果SSR总体异常率为73．4％（141／192）；在无周围神经损害症状和自主神经功能损害症状的患者中，SSR异常率分别为71．5％（27／38）和68．8％（11／16）；性别、年龄、病程及有无自主神经功能损害症状对SSR异常率无影响（P均〉0．05）。SSR上肢波幅（Amp）与脂蛋白B（ApoB）、低密度脂蛋白胆固醇（LDL-C）和胆固醇（CHO）呈正相关；下肢潜伏期（Lat）与餐后2h血糖（2hPBG）、舒张压（DBP）均呈正相关；下肢Amp与ApoA1、ApoB、LDL-C和CHO呈正相关（P〈0．05或P〈0．01）。阴虚证、血瘀证出现频率〉50％；〉60岁组阳虚证比例及积分均显著高于≤60岁组（P〈0．05和P〈0．01）；病程长者血瘀证、阳虚证积分均显著增高（P均〈0．01）；有自主神经功能损害症状患者的气虚证和阴虚证积分均显著高于无自主神经功能损害症状者（P均〈0．01）；SSR异常组的阴虚证积分显著低于正常组（P〈0．05）。相关分析显示：SSR的四肢Lat与气虚证积分呈负相关（-0．316〈r值〈-0．157，P〈0．05或P〈0．01）；右上肢Amp与阳虚证、血瘀证积分均呈负相关（阳虚证r=-0．207，P=0．006；血瘀证r=-0．162，P=0．032）。结论SSR有助于发现糖尿病的亚临床神经病变，可作为评价T2DM患者早期自主神经及小纤维神经病变的敏感指标；血糖、血脂和血压可影响SSR参数。DPN患者阳虚、血瘀程度随病程延长和年龄增长渐进加重，气虚、阳虚和血瘀3种证候的病情程度对SSR参数的异常有一定影响。     

Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients

Dynamic artery blood pressure (Finapres) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady-state artery blood pressure level to measure sympathetic vasomotor function in healthy subjects (n=23, age 35±9 years; mean±SD) and in type I diabetic patients without autonomic neuropathy (AN) (group 1: n=18, 38±13 years), with AN but no cardiovascular drugs (group 2a: n=7, 44±11 years) and with both AN and cardiovascular drugs (group 2b: n=10, 47±7 years). Systolic and diastolic overshoot were similar in the control (15±13/15±11 mmHg) and group 1 subjects. Systolic overshoot disappeared in 57% of patients in group 2a (?1±9 mmHg; P<0·03), whereas artery blood pressure still overshot in diastole (8±7 mmHg; NS). Systolic overshoot disappeared in all patients in group 2b (?22±22 mmHg; P<0·0006) and diastolic overshoot disappeared in 60% of these patients (?6±16 mmHg; P=0·0006). Systolic early steady-state level was not lower in group 2a than in group 1 (NS), but it was impaired in group 2b (P<0·006), in which six diabetic patients had a pathological response beyond the age-related reference values. There was a strong association between the overshoot and steady-state levels (P for χ²<0·001, n=58). Overshoot of the control subjects and patients in group 2b correlated to their respective steady-state blood pressure levels (r≥0·76; P≤0·001). In conclusion, baroreceptor reflex-dependent over-shoot of the artery blood pressure after active standing up diminishes with the development of AN and it is associated with the early steady-state level of the artery blood pressure.     

Cardiovascular autonomic nervous system tests: reference values in young people (15-19 years) and influence of age and gender

Objective: The aim of this study was to determine values of the deep breathing test (DB), orthostatic test (OT) and Valsalva manoeuvre (VM) parameters in young people and influence of age and gender. Methods: A total of 206 healthy subjects (100 girls, 106 boys) at the age of 15–19 years, BMI 21·3±2·3 (mean ± SD) were examined by system Varia Pulse TF3. Results: Reference values of DB, OT, VM parameters are presented as arithmetic mean ± SD and percentiles (P₉₀, P₇₅, P₅₀, P₂₅, P₁₀). In the whole group HRrest was lower in 19‐year‐old group, in OT this difference was significant already in 18‐year‐old group compared with 15‐year‐old group. DB: I/E was significantly increased in 19‐year‐old group compared with 15‐year‐old group. HRrest was higher in girls compared with boys in the whole group. DB: I/E was significantly lower in girls compared with boys. OT: 30:15 and HRmax/HRrest were significantly decreased in girls compared with boys. Conclusion: Reference values of DB, OT, VM parameters were determined in young people at the age of 15–19 years. The most sensitive test for ascertainment of developmental changes was test of deep breathing. I/E was increased in the 19‐year‐old group compared with 15‐year‐old group indicating an increase of vagal activity. Girls had decreased some parameters of deep breathing and orthostatic test compared with boys in the same group (15–19 years).     

Sonography of entrapment neuropathies in the upper limb (wrist excluded)

The progressive refinement of broadband transducers with frequencies higher than 10 MHz and improved near-field resolution has enhanced the potential of sonography to evaluate a variety of nerve entrapment syndromes occurring in the upper limb, such as suprascapular neuropathy in the area of the spinoglenoid-supraspinous notch, the quadrilateral space syndrome (axillary neuropathy), radial neuropathy in the area of the spiral groove, the supinator syndrome (posterior interosseous neuropathy), the cubital tunnel syndrome (ulnar neuropathy), and the Kiloh-Nevin syndrome (anterior interosseous neuropathy). In these settings, high-resolution sonography can depict changes in the nerve's shape and echotexture and can depict many extrinsic causes of nerve entrapment.     

颈交感神经干离断对CCl_4所致大鼠肝损伤肝功能的影响

目的探讨大鼠颈交感神经干离断后对CCl4所致肝损伤的影响,了解交感神经对肝脏功能的调控机制。方法健康SD大鼠30只随机分为3组:A组正常对照组、B组假手术组、C组右颈交感干离断组,按照文献报道方法加以改进制作颈交感干离断模型。动物模型建立成功后,应用CCl4制作急性肝损伤模型。各组大鼠经不同处理后同一时段处死。检测各项肝功能指标及库伦阵列-高效液相色谱法测定肝组织内NE浓度。结果在CCl4所致肝损伤的情况下,颈交感神经干离断组AST、ALT、TBIL与假手术组比较显著降低(P0.05);Alb、PA较假手术组升高(P0.05)。肝组织内NE浓度较假手术组明显降低(P0.01)。结论大鼠颈交感神经干离断有利于肝脏蛋白的合成、胆红素的代谢、可减轻CCl4所致肝损伤时肝功能损害,可以减轻炎症反应。交感神经活化在炎症早期具有促炎效应。     

18F‐Fluorine‐18‐l‐dihydroxyphenylalanine (18F‐DOPA) positive isolated peritoneal carcinomatosis from a MENII‐related medullary thyroid carcinoma. About an atypical metastatic site and utility of 18F‐FDOPA

A patient, operated for a medullary thyroid carcinoma (MTC) with a positive RET mutation, showed several peritoneal nodes on a computed tomography (CT), with increased Thyrocalcitonine. A ¹⁸F‐Fluorine‐18‐l ‐dihydroxyphenylalanine (18‐F‐FDOPA) positron emission tomography (PET/CT) showed isolated tracer uptake on the nodes. A biopsy confirmed that it was from the MTC, with the same RET mutation as in blood.     

The influence of local skin heating and reactive hyperaemia on skin blood flow abnormalities in patients with reflex sympathetic dystrophy (RSD)

Abstract. Skin blood flow in reflex sympathetic dystrophy (RSD) patients has been reported to develop from an increase at an early stage to a decrease at later stages. So far, it remains unclear whether these abnormalities are solely of microcirculatory origin, and result from functional vasospasm or structural vessel wall changes. Eighty-seven RSD patients were categorized as follows: stage I in case of a stationary warmth sensation; stage II in case of an intermittent warmth and cold sensation; and stage III in case of a stationary cold sensation. Laser Doppler flowmetry (LDF) was used as a measure of total skin blood flow and transcutaneous oximetry (TCPO2) as a measure of vascular reactivity in the more superficial skin layers. Local skin heating and reactive hyperaemia were used to study the relative reserve capacity of skin microvessels. Finapres was used to assess digital arterial pressures. As compared to healthy volunteers ( n =16), LDF under control conditions demonstrated an increase in skin blood flow at stage I ( P <0.01). A decrease in skin blood flow under control conditions was seen at stages II ( P <0.05) and III ( P <0.05), but the relative flow reserve capacity, as measured with LDF, was not impaired at these stages. Regression analysis did not show a relation between LDF parameters and duration of the syndrome. TCPO2 revealed no differences between patient groups and controls. Regression analysis did not demonstrate a relation between TCPO2 parameters and duration of the syndrome. Digital systolic blood pressures were increased at stages II ( P <0.05) and III ( p <0.001). These findings indicate that abnormalities in skin blood flow, as observed in RSD patients, are of microcirculatory origin. The observed decrease in skin blood flow at stages II and III most likely results from functional vasospasm rather than from structural vessel wall changes.     

Comparison between Fractional Turnover Rate of Endogenous Plasma Triglycerides and of Intralipid® (Intravenous Fat Tolerance Test) in Man*

Abstract. The validity of the intravenous fat tolerance test (IVFTT) as a tracer for the fractional turnover rate of endogenous plasma triglycerides (TG) has been studied in 32 fasting men with either normal or elevated plasma TG concentrations. The endogenous plasma TG turnover was determined by sampling arterial and hepatic vein blood, determination of splanchnic net secretion of plasma TG and calculation of fractional TG turnover rate. Later the fractional elimination rate of exogenous TG was determined following a single IV injection of Intralipid® (IVFTT). The TG fractional removal rate constants derived from these two tests were significantly correlated (r = 0.6-0.7) but IVFTT gave higher absolute values. A statistical evaluation showed that the error for the determination of the fractional turnover rate of endogenous TG and the IVFTT were about 30–50% and 10% respectively. It is probable that the correlation would have been still better if the error for the estimation of endogenous plasma TG turnover had been lower. A significant negative correlation was found between very low density lipoprotein-TG concentration and fractional removal rate of both endogenous and exogenous plasma TG (r = ?0.7–0.8).     

Comparison between Fractional Turnover Rate of Endogenous Plasma Triglycerides and of Intralipid® (Intravenous Fat Tolerance Test) in Man*

Abstract. The validity of the intravenous fat tolerance test (IVFTT) as a tracer for the fractional turnover rate of endogenous plasma triglycerides (TG) has been studied in 32 fasting men with either normal or elevated plasma TG concentrations. The endogenous plasma TG turnover was determined by sampling arterial and hepatic vein blood, determination of splanchnic net secretion of plasma TG and calculation of fractional TG turnover rate. Later the fractional elimination rate of exogenous TG was determined following a single IV injection of Intralipid® (IVFTT). The TG fractional removal rate constants derived from these two tests were significantly correlated (r= 0. & -0.7) but IVFTT gave higher absolute values. A statistical evaluation showed that the error for the determination of the fractional turnover rate of endogenous TG and the IVFTT were about 30–50% and 10% respectively. It is probable that the correlation would have been still better if the error for the estimation of endogenous plasma TG turnover had been lower. A significant negative correlation was found between very low density lipoprotein-TG concentration and fractional removal rate of both endogenous and exogenous plasma TG (r=?0.7–0.8).     

红细胞内钾与血浆钾比值(RPRP)的测定方法及其临床意义

目的探讨红细胞内钾与血浆钾比值(RPRP)的测定方法及其临床意义。方法收集111名无继发性高血压者(具不同程度腹部胀气、精神不振、四肢无力、原发性低血压等),取肘静脉血样,经样品特殊处理后用电极法测定血浆钾、红细胞内钾,计算出RPRP,用多元回归方法比较RPRP与症状之间的关系。结果RPRP与经常性腹部胀气、经常性四肢无力、经常性精神不振、原发性低血压等的回归系数分别为0.195,0.232,0.270,0.315,OR值分别为1.215(1.029~1.434,95%CI),1.261(1.059~1.503,95%CI),1.311(1.065~1.616,95%CI),1.371(1.175~1.567,95%CI)。结论RPRP是经常性腹部胀气、经常性四肢无力、经常性精神不振、原发性低血压的敏感指标,为其危险因素,RPRP的正常值上限在27.57~30.92之间。提示RPRP可能是人体细胞内外钾分布紊乱的诊断指标。     

Age-associated decline of hepatic handling of cholephilic anions in humans is reverted by S-adenosylmethionine (SAMe)

Decreased fluidity of hepatocyte plasma membrane may contribute to the age-associated changes of liver function. This study aimed at investigating whether the hepatic clearance of organic anions declines with age and whether S-adenosylmethionine (SAMe), a substance proven to be effective in reversing the age-related decrease of membrane fluidity, might influence this process. Nicotinic acid (NA) half-life and serum bilirubin pharmacokinetics after NA load (5.9 umol/kg body weight i.v.) were studied in 10 healthy young males (YM) aged 14-28 years and in 10 healthy elderly males (EM) aged 65-81 years, before and after SAMe administration (800 mg/day intravenously for 10 days). At baseline, EM showed serum total bilirubin (STB) levels significantly higher than YM. Similarly, the bilirubinaemic mean curves, STB peak and STB time curve concentration after NA load, expressed as area under the curve (AUC), were significantly higher in EM than in YM (p<0.01). NA half-life was also significantly prolonged in the aged group (p<0.001). SAMe treatment was followed by a significant decrease of basal STB, STB peak and AUC of STB after NA load in EM (p<0.01 vs pre-treatment values) while NA half-life was significantly shortened in both groups (p<0.001). As NA and bilirubin share a common carrier protein for hepatic uptake, bilitranslocase, the changes observed in EM may be attributed to the reduced lateral mobility of hepatocyte plasma membrane proteins occurring with age. SAMe, by improving membrane fluidity, may increase the diffusion coefficient of bilitranslocase restoring the hepatic handling of organic anions.     

血浆脑钠肽水平对冠心病诊断价值的初步探讨

目的通过检测观察冠心病患者血浆中脑钠肽(BNP)水平的改变,并与其肌钙蛋白I(cT n I)水平和高敏感性C反应蛋白(hs CRP)水平变化相比较,初步探讨将BNP作为冠心病临床诊断和治疗的标志物的可靠性。方法2004年3~11月,以分层随机抽样法获取西安地区健康人群血浆样本195份(男性132名,女性63名),西京医院住院患者血浆279份(包括129名冠心病、60名糖尿病、62名肺病疾患、28名单纯眼部疾患),利用微粒子酶免分析法和动态定时散射比浊法分别检测上述血浆BNP浓度、cT n I浓度及hs CRP浓度;将以上数据进行统计学分析,比较冠心病组与非冠心病组的差异显著性。结果统计学分析证实:冠心病组与正常组在BNP水平、cT n I水平及hs CRP水平上均存在非常显著性差异(P<0.01),而其中又以BNP水平差异显著性最大(P=0.001);糖尿病组、肺病组以及眼科阴性对照组的BNP浓度结果与正常组比较则显示无统计学意义(P>0.05)。结论血浆BNP浓度在冠心病患者中显著升高,进一步显示了其在心脏疾患中潜在的临床价值。