Stressful training changes endogenous neurotransmitters in human plasma

Stress is defined as a state of disharmony or threatened homeostasis. The purpose of the present study was conducted to reveal the effect of intensive training as rangers of Japan Ground Self Defence Force (JGSDF), which would be a strong stressor, on the level of neurotransmitters related with endogenous control of pain. Subjects were seven uniformed members (aged 19–21 years old) who underwent ranger training in the 8th Division of the JGSDF. Before and after the 40 days hard training, the levels of serotonin, β‐endorphin and three fractions of catecholamine in plasma were routinely measured. The levels of serotonin, β‐endorphin, noradrenaline and dopamine were significantly increased after the ranger training. A close relationship between the changes in skin pain threshold previously reported and the present levels of serotonin, β‐endorphin, noradrenaline and dopamine was observed in four of the seven rangers. These findings suggest that the intensive training changes level of some endogenous transmitters which might be related with stress‐induced analgesia through descending control of pain. Copyright © 2004 John Wiley & Sons, Ltd.     

纳络酮治疗急性重型颅脑损伤患者血浆内皮素含量变化及其临床意义

目的 探讨纳络酮治疗急性重型颅脑损伤患者血浆内皮素（ET）含量变化及其临床意义，评价纳络酮治疗急性重型颅脑损伤的意义。方法 观察了52例纳洛酮治疗急性重型颅脑损伤患者血浆ET含量在治疗前1d、治疗后3、8d及2周的变化，并且以46例颅脑损伤患者按常规治疗作对照组。结果 颅脑损伤24h内两组患者血浆内皮素较正常人均明显升高（P〈0．05），伤后第3天、第8天两治疗组血浆内皮素较治疗前均明显下降（P〈0．05），但纳络酮治疗组低于常规治疗组（P〈0．05），治疗2周后两组ET水平基本恢复到正常水平。结论 急性重型颅脑损伤患者血浆内皮素含量明显升高，与病情轻重相关，纳络酮治疗较常规治疗能更迅速地降低血浆ET水平。     

Is β‐endorphin significant in the control of the male sexual response?

It has been assumed that β‐endorphin, belonging to the family of opiodergic neuropeptides, might facilitate the inhibition of the male sexual response; however, its role in the control of the penile erectile tissue remains to be elucidated. This study aimed to evaluate in healthy men the course of β‐endorphin in the systemic and cavernous blood through different stages of sexual arousal. Thirty‐four (34) men were exposed to erotic stimuli to induce penile tumescence and rigidity. Blood was aspirated from the corpus cavernosum and a cubital vein during the penile conditions flaccidity, tumescence, rigidity and detumescence. Plasma levels of β‐endorphin were determined by means of radioimmunometric methods. The effects of β‐endorphin on isolated human penile erectile tissue were investigated in vitro. β‐endorphin did not induce a contractile response of the cavernous tissue or reverse the contraction induced by noradrenaline. β‐endorphin decreased in the systemic blood when the penis became tumescent and rigid and increased during detumescence. In the cavernous blood, no alterations in β‐endorphin concentrations were observed. The drop in β‐endorphin observed during tumescence and rigidity seems likely to reflect the inhibition of the opioidergic input with the beginning of sexual arousal.     

Changes in plasma sulfoconjugated catecholamines during perioperative period of cardiac operations--effect of continuous infusion of dopamine]

In order to clarify the physiological significance of sulfate conjugation of catecholamines and the effect of continuous dopamine infusion on the conjugate formation, we measured the plasma levels of free and sulfoconjugated catecholamines during the perioperative period of cardiac operations. The study group consisted of 12 adult patients who underwent cardiac operations. There were 13 study intervals starting from a day before each operation to 72 hours after each operation for the collection of blood specimen. The plasma levels of free and sulfoconjugated catecholamines were measured by radioenzymatic assay. The plasma levels of free dopamine did not show significant change by the induction of anesthesia, but they increased rapidly after the start of dopamine infusion to the level of 7654.9 +/- 731.7 pg/ml. Thereafter, the plasma free dopamine levels remained steady during the 24 hours after operation at 7516.7 pg/ml to 8449.2 pg/ml. On the other hand, the plasma levels of conjugated dopamine increased progressively by dopamine infusion during the 24 hours after operation. The plasma levels of free adrenaline increased significantly to the level of 1049.5 +/- 117.7 pg/ml by dopamine infusion, and lasted with plateau until the 24th hour after operation at the range of 1076.8 pg/ml to 1218.9 pg/ml. Conjugated adrenaline followed a similar pattern to that of conjugated dopamine, with a progressive increase due to the infusion of dopamine. In the case of noradrenaline, free noradrenaline started to increase at the time of cardiopulmonary bypass and showed a further increase by dopamine infusion during the first hour after operation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of physical and mental training on plasma beta‐endorphin level and pain perception after intensive physical exercise

The intention of the study was to investigate a possible correlation between increase in circulating blood level of beta‐endorphin and decrease in pain perception after short‐term intensive physical exercise. In addition, we wanted to see if plasma beta‐endorphin level and pain perception were influenced by regular physical or mental training and if there was any difference in response between trained and untrained subjects. Twenty physically trained males were studied before and after a 6‐month intervention period while practising regular physical endurance training. Eleven of them were randomized to perform daily additional mental training (ACEM meditation). Nine untrained males served as control subjects and were investigated only at baseline. All participants were tested for maximum oxygen uptake (VO_2max) during treadmill exercise, and pain perception measured by an ischaemic pain test was performed just before and after VO_2max. Blood samples analysed for beta‐endorphin were drawn before and after the tests. There was a substantial decrease of 47 per cent (p < 0.005) in basal plasma beta‐endorphin level after the intervention. The plasma beta‐endorphin level increased two‐fold (p < 0.01) in response to the VO_2max test. The subjects experienced post‐exercise hypoalgesia (p < 0.001), but there was no correlation between the exercise‐associated opioid hyperendemia and the hypoalgesia. No difference was found between trained and untrained subjects regarding the circulating blood level of beta‐endorphin or the exercise‐induced hypoalgesia. Practising regular meditation had no influence on beta‐endorphin level or pain tolerance level. Peripheral beta‐endorphin level and pain perception are modulated by intensive physical exercise and by regular physical, but not by mental training. It could be speculated that the observed initial high basal level of beta‐endorphin is due to pre‐experimental stress and tension. Copyright © 2001 John Wiley & Sons, Ltd.     

Dopamine Infusion in Man. Plasma Catecholamine Levels and Pharmacokinetics

Dopamine is widely used in the treatment of hypotensive conditions and/or impending renal failure, but the plasma levels of dopamine and other catecholamines in association with dopamine infusion are not known. Plasma catecholamines and dopamine pharmacokinetics during and after dopamine infusion were therefore studied in man. Two and 5 μg - kg^-1 - min^-1 of dopamine were infused for 30 min in two groups of five patients. Dose-dependent mean steady state levels with fairly large interindividual variations were reached within 5 min. Elimination of dopamine from plasma after termination of infusion had a biphasic course with t 1/2 around 1 min and t 1/2 β about 9 min in both groups. Noradrenaline plasma levels and blood pressure increased significantly in the 5 μg group. It is suggested that the vasoconstriction with deleterious effects on tissue perfusion, seen in conjunction with high-dose dopamine infusion, may be due to increased noradrenaline levels.     

Plasma noradrenaline and dopamine in burn patients

The sympatho-adrenal activity was studied in 10 patients after moderate and severe burn injuries. During the first days high levels of noradrenaline and dopamine were found in plasma. There seems to be a correlation between critical clinical condition and increasing levels of noradrenaline and dopamine. The endogenous dopamine released may be of importance for improvement of renal function.     

绝经后妇女利维爱治疗前后血浆β-内啡肽变化

用放射免疫法测定６２例绝经后妇女及其中１０例应用利维爱治疗前后的血浆β 内啡肽（β ＥＰ）水平。结果：绝经后血浆β ＥＰ水平较育龄妇女黄体期显著下降。应用利维爱（１２５ｍｇ／日）治疗后血浆β ＥＰ及血清雌二醇显著上升，卵泡刺激素及黄体生成素显著下降，同时潮红潮热等症状缓解。结论：（１）绝经后卵巢激素减少，内源性鸦片肽戒断可能与绝经后某些症状有关；（２）利维爱能提高血浆β ＥＰ水平，改善绝经后症状。     

Exercise‐Induced Changes in Atrial Peptides in Relation to Neuroendocrine Responses and Fluid Balance in the Horse

Previous data show that, in horses, plasma atrial natriuretic peptides (ANP and NT‐ANP) remain elevated for a long time after exercise. To study whether exercise‐induced changes in hormonal and fluid balance explain this, we measured plasma concentrations of COOH‐ and NH₂‐terminal atrial natriuretic peptides (ANP_99–129 and NT‐ANP_1–98) together with arginine vasopressin (AVP), adrenocorticotrophin (ACTH), β‐endorphin, cortisol, catecholamines, and indicators of fluid balance in six Finnhorses after a graded submaximal exercise test on a treadmill. After exercise, AVP and catecholamines diminished rapidly; atrial peptides, ACTH, β‐endorphin, and cortisol remained elevated longer. ANP reached its peak value at 5 min and NT‐ANP at 30 min post‐exercise. At 60 min, ANP was still significantly increased and NT‐ANP even above its level at the end of exercise. The different temporal patterns of ANP and NT‐ANP are most probably explained by differences in their plasma half‐lives. The post‐exercise increase in NT‐ANP indicates that the release of atrial peptides is stimulated during recovery after exercise. The rapid decrease in AVP and catecholamines suggests that these hormones do not explain the long‐lasting increase in atrial peptides. Cortisol remained elevated longer and it may have contributed to some extent. After exercise, the packed cell volume (PCV) decreased more slowly than plasma total protein and electrolytes, which refers to a slow post‐exercise return in blood volume. Taken together, the present results show that the long‐lasting post‐exercise increase in plasma atrial peptides in horses is most probably explained by elevated central blood volume and that the role of vasoactive hormones is small.     

CSF Neurotransmitter metabolites in comatose head injury patients during changes in their clinical state

Summary The main metabolites of noradrenaline, serotonin, and dopanine, methoxyhydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA), respectively, were assessed in CSF samples of patients in coma after severe head injury, the first days after the accident and again after an improvement (13 patients) or deterioration (7 patients) in their clinical state, evaluated by the score on the Glasgow Coma Scale.Improvement was accompanied by significant decreases in HVA and 5HIAA. In the patients who deteriorated, the levels of the three metabolites remained high.The results show that the increased turnover of CNS neurotransmitters in severe head injury normalizes during recovery. The use of noradrenaline, dopamine, and serotonin antagonists in brain injury experimental models may clarify the role of the increased biogenic amine turnover in the processes that lead to recovery. We propose relevant pharmacological intervention influencing neurotransmission in severe head injury.     

Plasma catecholamines and alpha 1-adrenoceptor function in hemodialysis-associated hypotension

alpha 1-Adrenoceptor function and plasma catecholamine levels were investigated in chronically hemodialyzed patients with and without hemodialysis-induced hypotension. In the interdialytic period blood pressure responses as well as the mydriasis after topical application of the alpha 1-selective agonist phenylephrine were not significantly different in patients with or without hypotension during dialysis, although patients with hypotension were more susceptible to miosis induced by the muscarinergic agonist carbachol. In the normotensive group the blood pressure increasing effect of phenylephrine was attentuated after 120 min of hemodialysis therapy. Plasma noradrenaline levels were not significantly different in both groups and did not change significantly during hemodialysis, while plasma dopamine was significantly increased in the hypotensives. Thus, evidence for a pathophysiological role of a postsynaptic alpha-adrenoceptor dysfunction in hemodialysis-induced hypotension was lacking.     

Kinin system responses in sepsis after trauma in man

We measured the level or activity of plasma kallikrein, kininase I (carboxypeptidase N), trypsin and kallikrein inhibitors. The concentration of kininogen substrate was established by activating plasma prekallikrein with an added insoluble prekallikrein activator preparation. The blood samples were collected from normal donors and from young men hospitalized with combat trauma complicated by gram-negative sepsis. Twelve of these patients survived and six died during the study. Some of the patients had no measurable kininogen at the beginning of the hospitalization. In those patients who survived, the kininogen levels declined profoundly toward the end. This drop was accompanied by a decrease in the prekallikrein level. The levels of the other three proteins were not significantly different between the two groups of patients. The results suggest the liberation of bradykinin in septic shock.     

The mechanism and effect of chronic electrical stimulation of the globus pallidus for treatment of Parkinson disease

OBJECT: Although chronic electrical stimulation of the globus pallidus (GP) has been shown to ameliorate motor disabilities in Parkinson disease (PD), the underlying mechanism remains to be clarified. In this study the authors explored the mechanism for the effects of deep brain stimulation of the GP by investigating the changes in neurotransmitter levels in the cerebrospinal fluid (CSF) during the stimulation. METHODS: Thirty patients received chronic electrical stimulation of the GP internus (GPi). Clinical effects were assessed using the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr Staging Scale at 1 week before surgery and at 6 and 12 months after surgery. One day after surgery, CSF samples were collected through a ventricular tube before and 1 hour after GPi stimulation. The concentration of neurotransmitters such as gamma-aminobutyric acid (GABA), noradrenaline, dopamine, and homovanillic acid (HVA) in the CSF was measured using high-performance liquid chromatography. The treatment was effective for tremors, rigidity, and drug-induced dyskinesia. The concentration of GABA in the CSF increased significantly during stimulation, although there were no significant changes in the level of noradrenaline, dopamine, and HVA. A comparison between an increased rate of GABA concentration and a lower UPDRS score 6 months postimplantation revealed that the increase in the GABA level correlated with the stimulation-induced clinical effects. CONCLUSIONS: Stimulation of the GPi substantially benefits patients with PD. The underlying mechanism of the treatment may involve activation of GABAergic afferents in the GP.     

A comparative study on the effect of halothan-N2O-anaesthesia and neuroleptanalgesia on plasma catecholamines during the intra- and postoperative period (author's transl)

The influence of neuroleptanalgesia and halothane-N2O-anaesthesia on the activity of the sympathetic nervous system was studied continuously in the intra- and postoperative period in 2 groups of 10 patients undergoing abdominal operations. In the neuroleptanalgesia-group the noradrenaline level in plasma rose continuously during the course of the operation and this increase was highly significant. The adrenaline level in plasma increased as well, however this increase did not depend on the duration of the operation. In the halothane-N2O-group only a small increase of both adrenaline and noradrenaline in plasma could be demonstrated intraoperatively. One hour after the end of the operation the plasma levels of adrenaline and noradrenaline were elevated in both groups. The noradrenaline level was even higher after neuroleptanalgesia. Four hours after the end of surgery the levels of adrenaline and noradrenaline started to decrease, but were still above the preanaesthetic level. The increase of the concentration of catecholamines in plasma indicating an activation of the sympathetic nervous system was not associated with a corresponding increase in heart rate and blood pressure intra- as well as postoperatively in either group. Only in the neuroleptanalgesia-group was there a small, but insignificant increase of the systolic and diastolic pressure postoperatively.     

Effect of Gosha-jinki-gan, a blended herbal medicine, on bladder activity in rats

PURPOSE: We investigated the effect of the blended herbal medicine Gosha-jinki-gan on bladder activity and the autonomic nervous system in rats. MATERIALS AND METHODS: A total of 42 female rats were divided into a control diet group of 21 and a Gosha-jinki-gan diet group of 21. Rats in the control diet group were fed a standard diet, while animals in the Gosha-jinki-gan were fed a special diet containing 1.08% Gosha-jinki-gan (TJ107, Tsumura Co., Tokyo, Japan). After 4 weeks 28 rats, including 14 in the control and 14 in the Gosha-jinki-gan group, underwent continuous cystometry with physiological saline or 0.1% acetic acid solution and bladder activity was recorded. The remaining 14 rats were anesthetized with halothane, and body weight, serum amino acid (glutamate and glycine) and plasma monoamine (noradrenaline, adrenaline, dopamine and serotonin) levels were measured. RESULTS: The amplitude of bladder contraction on continuous cystometry with physiological saline was lower in the Gosha-jinki-gan diet group than in the control diet group, and plasma dopamine and serotonin levels were also lower in the Gosha-jinki-gan group. When cystometry was done with 0.1% acetic acid, the interval between bladder contractions was shortened in the control and Gosha-jinki-gan groups. However, the interval and duration of bladder contractions were longer in the Gosha-jinki-gan than in the control group. CONCLUSIONS: These results suggest that Gosha-jinki-gan inhibits bladder activity by maintaining the balance of the sympathetic and parasympathetic nervous systems at a low level.     

Changes in plasma dopamine-β-hydroxylase activity during the perioperative period of cardiac surgery: An index of sympathetic nerve activity

To evaluate the usefulness of plasma dopamine--hydroxylase (DBH) activity as an index of sympathetic nerve activity during cardiac operations, we examined the serial changes in plasma DBH activity, in relation to the plasma noradrenaline (NA) level and hemodynamic parameters, in patients who underwent cardiac surgery. The plasma DBH activity decreased significantly after cardiopulmonary bypass, and remained low during dopamine (DA) infusion until 72 h after the operation. However, recovery of the hemodynamic parameters, being the mean arterial pressure, heart rate and cardiac index, was seen as early as 1–3 h postoperatively. It was therefore assumed that the plasma DBH activity takes a long time to recover after an operation. The time-course changes in the plasma NA level were quite different from the changes in DBH activity, with an apparent negative correlation being observed between them. Thus, there is a possibility that exogenously administered DA, as well as increased plasma NA, might inhibit DBH activity during cardiac surgery. Moreover, since catecholamines are often administered upon completion of cardiac surgery, measurement of the plasma catecholamine level would be inappropriate for evaluating real sympathetic nerve activity. From the results of this study, it is surmised that measurement of the plasma DBH activity could be useful for estimating the intrinsic sympathetic nerve activity of patients who have undergone cardiac surgery.     

Positive end-expiratory pressure increases plasma catecholamine levels in non-volume loaded dogs

Positive end-expiratory pressure (PEEP) is commonly used in the treatment of critically ill patients whose sympathetic nervous system is stressed; however, PEEP's actions on sympathetic nervous system activity are unknown. We therefore measured the plasma noradrenaline response (an index of sympathetic nervous system activity) to graded doses of PEEP in nine mongrel dogs. After 30 minutes at each level of PEEP, plasma noradrenaline concentrations increased from baseline mean values of 300 (SD 108) pg/ml to 388 (SD 225) pg/ml (P less than 0.05) at 5 cm, 433 (SD 255) pg/ml (P less than 0.01) at 10 cm and 1194 (SD 882) pg/ml (P less than 0.01) at 20 cm water pressure of PEEP. The increases in plasma noradrenaline concentrations correlated inversely (r = -0.43, P less than 0.01) with PEEP-induced changes in cardiac output. Plasma adrenaline levels did not change significantly in response to 5 or 10 cm of PEEP; however, plasma adrenaline increased, while heart rate and mean arterial blood pressure fell, at 20 cm water pressure of PEEP (P less than 0.05). Within 15 minutes after discontinuation of PEEP, the plasma catecholamine concentrations returned to baseline levels. Conclusions: 1. PEEP significantly increases sympathetic nervous system activity in a rapid, dose-dependent, reversible manner; 2. the PEEP-induced increases in sympathetic activity may explain the reductions in organ blood flow which others have observed following the initiation of PEEP; 3. PEEP-related changes in sympathetic nervous system activity are a consequence of PEEP-induced reductions in cardiac output.     

EFFECTS OF PANCURONIUM AND ALCURONIUM ON THE CHANGES IN ARTERIAL PRESSURE AND PLASMA CATECHOLAMINE CONCENTRATIONS DURING TRACHEAL INTUBATION

The changes in the plasma concentrations of noradrenaline, adrenalineand dopamine, during tracheal intubation, were studied in 17patients. Nine patients received pancuronium and eight alcuroniumto produce neuromuscular blockade. In the patients receivingpancuronium, intubation of the trachea was accompanied by anincrease in mean arterial pressure, and in the plasma concentrationsof noradrenaline and adrenaline. In the alcuronium group, therewere no significant changes in the plasma concentrations ofany catecholamine, nor any change in mean arterial pressurein response to intubation of the trachea.     

Haemodynamic and neurohumoral effects of xenon anaesthesia A comparison with nitrous oxide

Thirty-two patients were randomly allocated to be anaesthetised either with nitrous oxide or xenon. Those who received nitrous oxide required significantly more fentanyl peroperatively. Arterial blood pressure and heart rate were adequately controlled during surgery in both groups. Plasma noradrenaline and prolactin increased peroperatively in both groups, but plasma adrenaline and cortisol, which increased in the nitrous oxide group, did not change in the xenon group. Growth hormone was below control in those given xenon, but not in the nitrous oxide group, while dopamine remained unchanged in both groups. Postoperative plasma concentrations of noradrenaline, adrenaline, cortisol and prolactin (in both groups) and dopamine (in the nitrous oxide group) were elevated, and slowly returned to control. No differences were seen between the two gases in effects on plasma sodium and potassium. Xenon, because of its favourable haemodynamic, neurohumoral and antinociceptive properties, deserves a more prominent place in anaesthetic practice than it has so far occupied.     

Cerebral Hemodynamics, Oxygen Uptake and Cerebral Arteriovenous Differences of Catecholamines Following E. coli Endotoxin in Dogs

In experimental endotoxic shock in dogs, a decrease in cerebral blood flow and an increase in cerebral metabolic rate of oxygen (CMRO2) have been shown to occur. In this situation the blood levels of adrenaline and noradrenaline are markedly elevated. The aim of the present study was to investigate whether a cerebral uptake of circulating catecholamines with a possible influence on CMRO2 takes place in the brain. In eight anaesthetized dogs, arterial blood, superior sagittal sinus blood and cerebrospinal fluid were analyzed for the concentrations of adrenaline, noradrenaline and dopamine before and up to 4 h after an injection of E. coli endotoxin 1.0-1.5 mg . kg-1. The blood levels of adrenaline and noradrenaline, but not dopamine, increased in response to the endotoxin. From about 30 min after the endotoxin injection, arteriovenous adrenaline and noradrenaline differences indicating a cerebral uptake were most often seen. Increased concentrations of noradrenaline, adrenaline and dopamine in cerebrospinal fluid were observed. Noradrenaline gave the highest concentrations and these were correlated to the CMRO2. In some animals the blood and cerebrospinal fluid concentrations of adrenaline seemed to be related. These results indicate that catecholamines might be of importance for the development of an increased CMRO2 in endotoxic shock.