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Background: Invasive cardiopulmonary exercise testing (iCPET) combines traditional cardiopulmonary exercise testing with invasive hemodynamic measurements to assess exercise intolerance, which can be caused by preload insufficiency (PI), characterized by low ventricular filling pressures and reduced cardiac output during exertion. We hypothesize that plasma catecholamine levels at rest and during exercise correlate with hemodynamic parameters in PI., Methods: We included adult patients who underwent iCPET for exercise intolerance and had plasma catecholamines measured at rest and peak exercise., Results: Among 84 patients, PI was identified in 57 (67.8 %). Compared to patients without PI, those with PI were younger [median (IQR) 37 (28, 46) vs 47 (39,55) years, p = 0.005] and had lower workload at peak exercise [81 (66, 96) vs 95 (83.5, 110.50) Watts, p = 0.006]. Patients with PI had higher heart rates at rest and peak exercise [87 (78, 97) vs 79 (74, 87) bpm, p = 0.04; and 167 (154, 183) vs 156 (136, 168) bpm, p = 0.01, respectively]. In all patients, epinephrine and norepinephrine at peak exercise directly correlated with peak workload (r:0.41, p < 0.001 and r:0.47, p < 0.001, respectively). Resting epinephrine was higher in patients with PI [136 (60, 210) vs 77 (41, 110) pg/mL, p = 0.02]. There was no significant difference in the change in catecholamines from rest to peak exercise between patients with or without PI., Conclusion: PI patients exhibited elevated heart rate and epinephrine at rest, indicating increased sympathetic activity. We did not find strong associations between catecholamines and cardiac filling pressures, suggesting that catecholamine levels are predominantly influenced by peak workload., Competing Interests: Declaration of competing interest The authors have no significant conflicts of interest with any companies or organizations whose products or services may be discussed in this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Catecholamines (CATs) are neurotransmitters and allostatic hormones whose plasma concentrations are physiologically modified in various species such as human, rats, mice and donkeys, with advancing age. However, currently these mechanisms are less well elucidated in horses and more specifically in mares. The hypothesis of this study was that, as in afore mentioned species, the CATs could experience physiological changes with advancing age. The objective of this study was to evaluate the concentrations of adrenaline (A), noradrenaline (NA), dopamine (DA), and serotonin (5-HT) in mares of different ages. Blood samples were drawn from 56 non-pregnant Spanish Purebred mares belonging to four different age groups: 6 to 9 years, 10 to 12 years, 13 to 16 years and > 16 years. The concentrations of A, NA, DA, and 5-HT were determined by competition EIA-Technical 3-CAt EIA, specifically validated for horses. Mares aged > 16 years showed lower A, DA, and 5-HT but higher NA concentrations than 6-9, 10-12, and 13-16 years (p < 0.05). Mares of 13-16 years showed lower A and higher NA than 6-9 and 10-12 years (p < 0.05). A and NA (r=-0.72; p < 0.05), and NA and 5-HT (r=-0.67; p < 0.05) were negatively correlated, and A and 5-HT (r = 0.74; p < 0.05) were positively correlated. Advanced age leads to a predominance of sympathetic nervous activity and lower serotonergic activity in non-pregnant mares., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general anesthesia in patients with PIH undergoing laparoscopic cholecystectomy., Methods: This prospective study included 557 adult patients who underwent laparoscopic cholecystectomy under general anesthesia. PIH was defined as a greater than 20% decrease in systolic blood pressure from the pre-induction value, a systolic arterial pressure of less than 90 mmHg, or both. Plasma concentrations of epinephrine and norepinephrine during the induction of general anesthesia were determined using enzyme-linked immunosorbent assay. Multivariate logistic regression analysis evaluated the association between the clinical factors and PIH., Results: Of the 557 patients, 390 had PIH, and the remaining 167 were allocated to the non-PIH group. Changes in blood adrenaline, noradrenaline levels, or both were more pronounced in the PIH than in the non-PIH group (p<0.05). Age, body mass index, a history of hypertension, preoperative systolic blood pressure, and propofol or sufentanil dose were independent predictors of PIH., Conclusion: The changes of blood catecholamines in patients with more stable hemodynamics during the induction of general anesthesia are smaller than that in patients with post-induction hypotension., Trial Registration: ChiCTR2200055549, 12/01/2022., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2024 Yao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Accurate diagnosis of pheochromocytoma and paraganglioma (PPGLs) is highly dependent on the detection of metanephrines and catecholamines. However, the systematic investigation on influencing factors including specimen (plasma or whole blood), anticoagulant, storage conditions, and interference factors need further confirmation., Methods: Blood with heparin-lithium or EDTA-K2 were collected, stability of epinephrine (EPI), norepinephrine (NE), dopamine (DA), metanephrine (MN), normetanephrine (NMN), 3-methoxytyramine (3-MT) in whole blood and plasma at room temperature and 4 °C for different storage times, stability of plasma MN, NMN and 3-MT at -20 °C and -80 °C were investigated. Plasma with hemoglobin (1 g/L, 2 g/L, 3 g/L, 4 g/L, 6 g/L), TG (<5 mmol/L, 5-8 mmol/L, >8 mmol/L) were prepared., Results: EPI, NE, DA were prone to degrade at room temperature, samples should be centrifuged at 4 °C. EPI and NE were stable in whole blood at 4 °C for 4 h and in plasma for 2 h. For MN, NMN, 3-MT, plasma can be stable at room temperature and 4 °C for at least 6 h, which is better than whole blood; there was no significant difference when stored at -20 °C and -80 °C for 7 days. Heparin-lithium had a slight advantage over EDTA-K2. EPI, NE, DA should not be performed when Hb > 1 g/L or TG > 5 mmol/L. MN, NMN, 3-MT should not be performed when Hb > 2 g/L, whereas TG had no interference., Conclusions: According to the actual clinical application scenario, this study provided a reliable basis for the accurate diagnosis of PPGLs.

Aims: To investigate the change of stress hormones, oxidative stress and insulin resistance (IR) in women with gestational diabetes mellitus (GDM) after supplement whey protein, in an attempt to gain insights into the prevention and treatment of GDM., Materials and Methods: 60 GDM women were recruited in this study, and 30 women received a preload drink containing 20 g whey protein as group GDM-W, and the other 30 women received control flavoring drink as group GDM, and the trial lasted for 14 days. Plasma epinephrine (E), noradrenaline (NE), and cortisol were detected; we also determined levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to assess IR., Results: In the GDM-W group, postprandial blood glucose was decreased significantly on 3, 5, 7, and 14 days (all p  < .05), plasma 2 h insulin was increased by 7.2, 8.6, and 20.5% on days 5, 7, and 14 ( p  < .05, .05, .01). HOMA-IR was decreased significantly on day 14 ( p  < .05). MDA was decreased by 20.7% on day 14 ( p  < .01), and anti-oxidative enzymes' SOD was decreased by 13.4% on day 14 ( p  < .05) and GSH was decreased by 16.7 and 29.1% on days 7 and 14 (both p  < .05). Stress hormones E and cortisol were decreased by 10.8 and 19.8%, respectively, on day 14 ( p  < .05). There was no significant difference in NE between the two groups within 14 days., Conclusions: Whey protein supplementation may improve hyperglycemia by alleviating stress disorder and oxidative stress injury in GDM women. This trial was registered at chictr.org.cn/as ChiCTR1800020413.

Fetuses with intrauterine growth restriction (IUGR) have high concentrations of catecholamines, which lowers the insulin secretion and glucose uptake. Here, we studied the effect of hypercatecholaminemia on glucose metabolism in sheep fetuses with placental insufficiency-induced IUGR. Norepinephrine concentrations are elevated throughout late gestation in IUGR fetuses but not in IUGR fetuses with a bilateral adrenal demedullation (IAD) at 0.65 of gestation. Euglycemic (EC) and hyperinsulinemic-euglycemic (HEC) clamps were performed in control, intact-IUGR, and IAD fetuses at 0.87 of gestation. Compared to controls, basal oxygen, glucose, and insulin concentrations were lower in IUGR groups. Norepinephrine concentrations were five-fold higher in IUGR fetuses than in IAD fetuses. During the EC, rates of glucose entry (GER, umbilical + exogenous), glucose utilization (GUR), and glucose oxidation (GOR) were greater in IUGR groups than in controls. In IUGR and IAD fetuses with euglycemia and euinsulinemia, glucose production rates (GPR) remained elevated. During the HEC, GER and GOR were not different among groups. In IUGR and IAD fetuses, GURs were 40% greater than in controls, which paralleled the sustained GPR despite hyperinsulinemia. Glucose-stimulated insulin concentrations were augmented in IAD fetuses compared to IUGR fetuses. Fetal weights were not different between IUGR groups but were less than controls. Regardless of norepinephrine concentrations, IUGR fetuses not only develop greater peripheral insulin sensitivity for glucose utilization but also develop hepatic insulin resistance because GPR was maintained and unaffected by euglycemia or hyperinsulinemia. These findings show that adaptation in glucose metabolism of IUGR fetuses are independent of catecholamines, which implicate that hypoxemia and hypoglycemia cause the metabolic responses.

Objective: To verify a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantification of catecholamines and their metabolites, and to validate its efficiency for the diagnosis of phaeochromocytomas and paragangliomas (PPGLs)., Methods: Plasma samples were pretreated with solid-phase extraction, followed by a 3-min UPLC-MS/MS analysis to quantify epinephrine (E), norepinephrine (NE), dopamine (DA), metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3-MT), simultaneously. The UPLC-MS/MS method was comprehensively verified and its diagnostic efficiency on PPGLs was tested using 7 PPGLs and 408 non-PPGLs patient plasma samples., Results: Using the developed method, the limit of detections (LODs) of the 6 analytes ranged from 0.0002 nmol/L (MN) to 0.0250 nmol/L (NE), while the lower limit of measuring intervals (LLMIs) ranged from 0.05 nmol/L (E, MN and NMN) to 0.10 nmol/L (NE and DA). The reportable ranges were 0.05-30.00 nmol/L for E, MN and NMN, 0.10-30.00 nmol/L for NE and DA, 1.00-300.00 pg/mL for 3-MT. No significant matrix effect was detected after correcting using internal standard. Besides, intra-day and inter-day precision were also within acceptance criteria with coefficient of variations (CVs) ≤ 15% and recoveries ranged from 95% to 115% for all the 6 analytes. The carryover effect was lower than 10%. Its diagnostic efficiency for PPGLs was significantly increased, the areas under the receiver operating characteristic (ROC) curves were increased from 68.7% to 89.1% (using E, NE and DA) to 75.2%-99.9% (using MN, NMN and 3-MT)., Conclusion: This study verified a rapid UPLC-MS/MS method for the determination of catecholamines and their metabolites in human plasma. It showed high diagnostic efficiency and will serve as an important tool to avoid the risk for missing patients with PPGLs., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Beta-blockers are still frequently used in cardiovascular diseases but may negatively influence the exercise capacity. The aim of the study was to analyze the effect of beta-blockade on physical performance and plasma level of catecholamine during different forms of exercise., Methods: Ten prehypertensive athletes (age: 25.1±2.5 years, BMI: 24.4±2.4 kg/m2) performed repeated incremental exercise and steady-state-tests without and with the cardioselective beta-blocker bisoprolol (5mg/day). The cardiopulmonary, metabolic and the catecholamine responses were monitored., Results: Beta-blocker treatment had no effect on maximum power output (Pmax), lactate and the maximal oxygen uptake (VO2max) (Pmax: 269.0±41.5 vs. 269.0±41.5 W; lactate: 8.7±2.6 vs. 8.6±3.2 mmol/L and VO2max: 3110±482 vs. 3077±425 mL/min, respectively; P not significant). Epinephrine and norepinephrine showed a similar exponential increase to maximum load with and without beta-blockade (epinephrinemax 1.92±1.8 vs. 1.93±1.3 nmol/L; P not significant; norepinephrinemax 12.78±7.9 vs. 16.89±12.2 nmol/L; P not significant). Beta-blockade lowered heart rate (HR) and systolic blood pressure (SBP) at rest and under maximum load (ΔHRrest: 10.6±11.1 bpm, P<0.05, ΔHR-Max: 27.8±6.6 bpm, P<0.01; ΔSBPrest: 19.4±9.3 mmHg, P<0.05, ΔSBPmax: 17.7±15.3 mmHg, P<0.01). The maximum oxygen pulse was higher in the tests performed under beta-blockade (IET: ΔVO2/HR: 3.1±2.2 mL/beat, P<0.01; SST: ΔVO2/HR: 3.4±1.4 mL/beat, P<0.001)., Conclusions: Despite beta blockade and resulting differences in cardiopulmonary regulation during the exercise tests, the maximal oxygen capacity and the catecholamine concentration was similar. Higher exercise intensities (>50% Pmax) are associated with a marked increase in plasma catecholamines, which are not influenced by treatment with bisoprolol 5 mg/day.

New Findings: What is the central question of this study? What are the mechanisms responsible for the decline in cognitive performance following exposure to acute normobaric hypoxia? What are the main findings and their importance? We found that (1) performance of a complex central executive task (n-back) was reduced at F I O 2 0.12; (2) there was a strong correlation between performance of the n-back task and reductions in S p O 2 and cerebral oxygenation; and (3) plasma adrenaline, noradrenaline, cortisol and copeptin were not correlated with cognitive performance., Abstract: It is well established that hypoxia impairs cognitive function; however, the physiological mechanisms responsible for these effects have received relatively little attention. This study examined the effects of graded reductions in fraction of inspired oxygen ( F I O 2 ) on oxygen saturation ( S p O 2 ), cerebral oxygenation, cardiorespiratory variables, activity of the sympathoadrenal system (adrenaline, noradrenaline) and hypothalamic-pituitary-adrenal axis (cortisol, copeptin), and cognitive performance. Twelve healthy males [mean (SD), age: 22 (4) years, height: 178 (5) cm, mass: 75 (9) kg, FEV 1 /FVC ratio: 85 (5)%] completed a four-task battery of cognitive tests to examine inhibition, selective attention (Eriksen flanker), executive function (n-back) and simple and choice reaction time (Deary-Liewald). Tests were completed before and following 60 min of exposure to F I O 2 0.2093, 0.17, 0.145 and 0.12. Following 60 min of exposure, response accuracy in the n-back task was significantly reduced in F I O 2 0.12 compared to baseline [82 (9) vs. 93 (5)%; P < 0.001] and compared to all other conditions at the same time point [ F I O 2 0.2093: 92 (3)%; F I O 2 0.17: 91 (6)%; F I O 2 0.145: 85 (10)%; F I O 2 12: 82 (9)%; all P < 0.05]. The performance of the other tasks was maintained. Δaccuracy and Δreaction time of the n-back task was correlated with both Δ S p O 2 [r(9) = 0.66, P < 0.001 and r(9) = -0.36, P = 0.037, respectively] and Δcerebral oxygenation [r(7) = 0.55, P < 0.001 and r(7) = -0.38, P = 0.045, respectively]. Plasma adrenaline, noradrenaline, cortisol and copeptin were not significantly elevated in any condition or correlated with any of the tests of cognitive performance. These findings suggest that reductions in peripheral oxygen saturation and cerebral oxygenation, and not increased activity of the sympathoadrenal system and hypothalamic-pituitary-adrenal axis, as previously speculated, are responsible for a decrease in cognitive performance during normobaric hypoxia., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

Studies have shown that stress-related catecholamines may affect cancer progression. However, little is known about catecholamine secretion profiles in head and neck cancer patients. The present study investigated plasma norepinephrine and epinephrine levels in head and neck squamous cell carcinoma (HNSCC) patients and patients with oral leukoplakia, as well as their association with clinicopathological and biobehavioral variables and anxiety symptoms. A total of 93 patients with HNSCC and 32 patients with oral leukoplakia were included. Plasma norepinephrine and epinephrine levels were measured by high performance liquid chromatography with electrochemical detection (HPLC-ED), and psychological anxiety levels were measured by the Beck Anxiety Inventory (BAI). Plasma norepinephrine and epinephrine concentrations were significantly higher in patients with oral and oropharyngeal squamous cell carcinoma (SCC) compared to non-cancer patients. Oral SCC patients displayed plasma norepinephrine levels about six times higher than oropharyngeal SCC patients, and nine times higher than oral leukoplakia patients (p < .001). Plasma epinephrine levels in oral SCC patients were higher compared to the oropharyngeal SCC (p = .0097) and leukoplakia (p < .0001) patients. Oropharyngeal SCC patients had higher plasma norepinephrine (p = .0382) and epinephrine levels (p = .045) than patients with oral leukoplakia. Multiple regression analyses showed that a history of high alcohol consumption was predictive for reduced plasma norepinephrine levels in the oral SCC group (p < .001). Anxiety symptom of "hand tremor" measured by the BAI was an independent predictor for higher plasma norepinephrine levels in HNSCC patients (β = 157.5, p = .0377), while the "heart pounding/racing" symptom was independently associated with higher plasma epinephrine levels in the oropharyngeal SCC group (β = 15.8, p = .0441). In oral leukoplakia patients, sleep deprivation and worse sleep quality were independent predictors for higher plasma norepinephrine levels, while severe tobacco consumption and higher anxiety levels were factors for higher plasma epinephrine levels. These findings suggest that head and neck cancer patients display sympathetic nervous system hyperactivity, and that changes in circulating catecholamines may be associated with alcohol consumption, as well as withdrawal-related anxiety symptoms., Competing Interests: The authors have declared that no competing interests exist.

The aim of the research was to determine in the experiment the content of catecholamines in serum of rats exposed to sodium fluoride. The studies were conducted on adult Wistar rats, subjected to oral exposure by means of a probe with aqueous solutions of sodium fluoride (SF) once daily, for 60 days at doses of 1/10, 1/100 and 1/1000 DL50, which correspondingly amounts to 20 mg/kg, 2 mg/kg and 0.2 mg/kg of body weight. Toxification of rats at a dose of 1/100 DL50 for 60 days and at a dose of 1/10 DL50 for 50 days was accompanied by an increase in blood levels of norepinephrine and epinephrine, indicating the hyperactivation of the mediator and hormonal parts of the sympathoadrenal system, and tension of the protective and adaptive reactions of the organism. Prolonged hypercatecholemia may become a pathogenic factor due to intensification of the quinidine route of oxidation of norepinephrine and epinephrine with the formation of reactive radicals and active forms of oxygen. Reduced serum content of catecholamines on the 60th day of oral administration at a dose of 1/10 DL50 reflects, on the one hand, a decrease in their tissue deposit, and, on the other, a decrease in the activity and reserve capacities of the sympathoadrenal system.

Background: Lipolysis is stimulated by activation of adrenergic inputs to adipose tissues. Our recent study showed that serum concentrations of fatty acid binding protein 4 (FABP4) are robustly elevated in patients with acute myocardial infarction and ventricular tachyarrhythmia, that display a marked activation of the sympathetic nervous system (SNS). However, it remains unknown whether circulating FABP4 concentrations are associated with exercise-induced SNS activation., Methods: Thirty one healthy volunteers underwent cardiopulmonary exercise testing on a cycle ergometer up to the workload levels below and above anaerobic threshold, low- and high-intensity exercise, respectively. Serial blood samplings were performed before and after exercise., Results: High-intensity exercise significantly increased serum concentrations of FABP4 and catecholamines, and their concentrations declined fast thereafter in a similar fashion. These changes were accompanied by little, if any, changes in other metabolic markers. Regardless of adiposity, percent change from baseline to peak FABP4 levels (%FABP4) was comparable in all subjects. Stepwise regression analysis revealed that %FABP4 was highly correlated with that in norepinephrine., Conclusions: Our study reveals the significant correlation between circulating FABP4 and norepinephrine levels during exercise testing. Together with the fact that FABP4 is secreted from adipocytes via β-adrenergic-mediated lipolytic mechanisms, this study suggests FABP4 as a potential biomarker for adrenergic overdrive., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Phaeochromocytoma localisation is generally reliably achieved with modern imaging techniques, particularly in sporadic cases. On occasion, however, there can be diagnostic doubt due to the presence of bilateral adrenal abnormalities, particularly in patients with mutations in genes predisposing them to the development of multiple phaeochromocytomas. In such cases, surgical intervention is ideally limited to large or functional lesions due to the long-term consequences associated with hypoadrenalism. Adrenal venous sampling (AVS) for catecholamines has been used in this situation to guide surgery, although there are few data available to support diagnostic thresholds. Retrospective analyses of AVS results from 2 centres were carried out. A total of 172 patients (88 men, 84 women) underwent AVS under cosyntropin stimulation for the diagnosis of established primary aldosteronism (PA) with measurement of adrenal and peripheral venous cortisol, aldosterone and catecholamines. Six patients (3 men, 3 women) with phaeochromocytoma underwent AVS for diagnostic purposes with subsequent histological confirmation. Reference intervals for the adrenal venous norepinephrine to epinephrine ratio were created from the PA group. Using the 97.5th centile (1.21 on the left, 1.04 on the right), the false negative rate in the phaeochromocytoma group was 0%. In conclusion, this study describes the largest dataset of adrenal venous catecholamine measurements and provides reference intervals in patients without phaeochromocytoma. This strengthens the certainty with which conclusions related to adrenal venous sampling for catecholamines can be drawn, acknowledging the procedure is not part of the routine diagnostic workup and is an adjunct for use only in difficult clinical cases., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

B-type natriuretic peptide (BNP) is a hormone released by the heart in response to volume load and exerts natriuretic properties. It is clinically used as a diagnostic and prognostic biomarker and investigated as a pharmacological agent in the therapy of heart failure. Here we investigate the changes in pituitary, adrenal, and thyroid hormones in response to BNP administration in a randomized single-blinded crossover study conducted in ten healthy men aged 21-29 yr. Participants received in two study sessions a continuous intravenous infusion during 4 h (once placebo and once 3 pmol·kg -1 ·min -1 BNP) and remained in supine position throughout the study. Circulating concentrations of pituitary, adrenal, and thyroid hormones, heart rate, and blood pressure were measured at baseline and hourly afterwards. BNP prevented the physiological decrease in cortisol during the late morning hours leading to elevated serum cortisol levels ( P = 0.022) and increased circulating epinephrine and norepinephrine concentrations ( P = 0.018 and P = 0.036, respectively). These hormone changes were accompanied by an increase in heart rate ( P = 0.019) but no differences in blood pressure. Taken together, the impact of BNP on the endocrine system extends beyond the well-known inhibition of the renin-angiotensin-aldosterone system and includes increased adrenergic activity and cortisol concentrations. This neuroendocrine activation might impact the outcome of therapeutical BNP administrations and should be further investigated in conditions associated with increased BNP secretion. NEW & NOTEWORTHY The heart hormone B-type natriuretic peptide (BNP) is increased in patients with heart failure, where it is thought to have beneficial effects by reducing the preload. Here we report that intravenous administration of BNP in men leads to increases in adrenal hormones cortisol, epinephrine, and norepinephrine. Cortisol and catecholamine levels are independent predictors of increased cardiovascular mortality risk; therefore, drugs targeting the BNP system should be evaluated regarding their effects on the neuroendocrine activation accompanying heart failure., (Copyright © 2017 the American Physiological Society.)

Posttraumatic acute diffuse brain swelling (PADBS) is characterized by serious brain bulk enlargement rapidly following trauma and is a major cause of elevated intracranial pressure and thus mortality. The pathogenesis of PADBS is not clearly understood, and the early stage alterations of catecholamine (CA) and adrenocorticotropic hormone (ACTH) levels in PADBS also remain largely unknown. The objective of this study was to investigate CA and ACTH levels in the patients with PADBS in the early stage and discuss the possible roles CA and ACTH in the pathogenesis of PADBS. It is a cross-sectional study. A group of patients with PADBS (n=10) was compared with a group of patients with severe brain injury (SBI) (n=33). A control group of healthy adults (n=25) was also included. Blood samples were obtained to measure levels of epinephrine (EPI), norepinephrine (NE), dopamine (DA), and ACTH as soon as the patients arrived at the neurosurgery department, which was done within 4h after trauma. Both SBI and PADBS groups of patients had higher levels of EPI, NE, DA, and ACTH than the control group. The PADBS group had significantly higher levels of EPI, NE, and ACTH than the SBI group. CA and ACTH levels are significantly increased in early stage PADBS. These results imply that CA and ACTH may play important roles in the pathogenesis of PADBS. To eliminate the effects of CA and ACTH at the early stage, and thereby protect the hypothalamus and brain stem, might be critical measures for treating patients with PADBS., (Copyright © 2017. Published by Elsevier Inc.)

Objective: Investigate and confirm the association between sympathoadrenal activation, endotheliopathy and poor outcome in trauma patients., Background: The association between sympathoadrenal activation, endotheliopathy, and poor outcome in trauma has only been demonstrated in smaller patient cohorts and animal models but needs confirmation in a large independent patient cohort., Methods: Prospective observational study of 424 trauma patients admitted to a level 1 Trauma Center. Admission plasma levels of catecholamines (adrenaline, noradrenaline) and biomarkers reflecting endothelial damage (syndecan-1, thrombomodulin, and sE-selectin) were measured and demography, injury type and severity, physiology, treatment, and mortality up till 28 days were recorded., Results: Patients had a median ISS of 17 with 72% suffering from blunt injury. Adrenaline and noradrenaline correlated with syndecan-1 (r = 0.38, P < 0.001 and r = 0.23, P < 0.001, respectively) but adrenaline was the only independent predictor of syndecan-1 by multiple linear regression adjusted for age, injury severity score, Glascow Coma Scale, systolic blood pressure, base excess, platelet count, hemoglobin, prehospital plasma, and prehospital fluids (100 pg/mL higher adrenaline predicted 2.75 ng/mL higher syndecan-1, P < 0.001). By Cox analyses adjusted for age, sex, injury severity score, Glascow Coma Scale, base excess, platelet count and hemoglobin, adrenaline, and syndecan-1 were the only independent predictors of both <24-hours, 7-day and 28-day mortality (all P < 0.05). Furthermore, noradrenaline was an independent predictor of <24-hours mortality and thrombomodulin was an independent predictor of 7-day and 28-day mortality (all P < 0.05)., Conclusions: We confirmed that sympathoadrenal activation was strongly and independently associated with endothelial glycocalyx and cell damage (ie, endotheliopathy) and furthermore that sympathoadrenal activation and endotheliopathy were independent predictors of mortality in trauma patients., Competing Interests: The authors declare no conflicts of interest.

Background: Elevated catecholamine levels might be associated with unfavorable outcome after traumatic brain injury (TBI). We investigated the association between catecholamine levels in the first 24 h post-trauma and functional outcome in patients with isolated moderate-to-severe TBI., Methods: A cohort of 174 patients who sustained isolated blunt TBI was prospectively enrolled from three Level-1 Trauma Centers. Epinephrine (Epi) and norepinephrine (NE) concentrations were measured at admission (baseline), 6, 12 and 24 h post-injury. Outcome was assessed at 6 months by the extended Glasgow Outcome Scale (GOSE) score. Fractional polynomial plots and logistic regression models (fixed and random effects) were used to study the association between catecholamine levels and outcome. Effect size was reported as the odds ratio (OR) associated with one logarithmic change in catecholamine level., Results: At 6 months, 109 patients (62.6%) had an unfavorable outcome (GOSE 5-8 vs. 1-4), including 51 deaths (29.3%). Higher admission levels of Epi were associated with a higher risk of unfavorable outcome (OR, 2.04, 95% CI: 1.31-3.18, p = 0.002) and mortality (OR, 2.86, 95% CI: 1.62-5.01, p = 0.001). Higher admission levels of NE were associated with higher risk of unfavorable outcome (OR, 1.59, 95% CI: 1.07-2.35, p = 0.022) but not mortality (OR, 1.45, 95% CI: 0.98-2.17, p = 0.07). There was no relationship between the changes in Epi levels over time and mortality or unfavorable outcome. Changes in NE levels with time were statistically associated with a higher risk of mortality, but the changes had no relation to unfavorable outcome., Conclusions: Elevated circulating catecholamines, especially Epi levels on hospital admission, are independently associated with functional outcome and mortality after isolated moderate-to-severe TBI.

Objectives: To explore whether the serum concentration of adrenaline (AD) and noradrenaline (NA) elevate and its correlation with oxygenation index (OI) in the patients of acute aortic dissection (AAD)., Methods: From April 2013 to December 2013, clinical data were collected from three groups of patients (38 cases of AAD in Group A, 28 cases of ascending aortic aneurysm in Group B, and 22 cases of angina in Group C). All patients received the measurement of serum concentrations of AD, NA and endotoxin (ET). Linear correlation was used to analyze the relationships between catecholamines (including AD and NA), ET and OI., Results: The baseline of the three groups showed no significant difference. The serum concentrations of AD, NA and ET in Group A were higher than those in Group B and Group C ( P <0.01), white OI was lower than that in Group B and Group C ( P <0.001). In the patients with AAD, the serum concentrations of AD and NA were positively correlated with ET, while both were negatively correlated with OI., Conclusions: Higher serum concentrations of AD and NA correlated with more severe acute lung injury in AAD patients.

Paroxysmal sympathetic hyperactivity (PSH) affects a significant minority of people in the intensive care unit after severe traumatic brain injury. Systematic research has yet to elucidate or quantify the extent of the role of the catecholamines or adrenocortical and thyroid axis hormonal influences in the condition. Data were prospectively collected on 80 consecutive patients, 18 of whom developed clinical signs of PSH (22.5%). Catecholamine and hormonal data were collected sequentially at 4-h intervals or during and between episodes of PSH. Evaluated variables showed 200-300% increases in catecholamines and, to a lesser extent, adrenocortical hormones during paroxysms. The majority of PSH episodes (72%) were noted to be in response to an observable triggering event. These changes were not observed in subjects without PSH. These data go some way to explain why PSH produces adverse consequences in survivors of TBI with the condition.

Background: Although the perioperative management of patients with pheochromocytoma has been improving recently, severe hypotensive episodes can occur that require postoperative catecholamine support and are challenging to manage. Our aim was to identify the clinical factors that predict prolonged postresection hypotension in patients after laparoscopic adrenalectomy for pheochromocytoma., Methods: The records of 73 Japanese patients who underwent unilateral laparoscopic adrenalectomy for pheochromocytoma were surveyed retrospectively. Patients were divided into 2 groups according to whether catecholamine support was needed after postoperatively. Clinical and biochemical data were evaluated at baseline and after operation., Results: Thirty-four of 73 patients (47%) required continuous infusion of catecholamine to maintain systolic blood pressure >90 mm Hg at the end of the operation. The median duration of postoperative catecholamine support was 17 hours (range, 3-130) in these 34 patients. On multivariate analysis, tumor size >60 mm, urinary epinephrine levels >200 μg/day, and urinary norepinephrine levels >600 μg/day were independent predictors of prolonged hypotension requiring postoperative catecholamine support. Tumor size and urinary norepinephrine levels were significantly correlated with the duration of postoperative catecholamine support., Conclusion: Larger tumor size and greater values of urinary epinephrine and norepinephrine levels were significant predictors of prolonged hypotension requiring postoperative catecholamine support. Moreover, tumor size and urinary norepinephrine levels were positively correlated with the duration of postoperative catecholamine support. Clinicians can identify and manage patients more effectively with a greater risk of prolonged hypotension after tumor resection using these preoperative clinical variables., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ(2)-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t = -6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents.

Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI., (Copyright © 2016 the American Physiological Society.)

Ginseng has a long history of use as a tonic for restoration of vigor. One example of ginseng-derived tonic effect is that it can improve physical stamina under conditions of stress. However, the active ingredient and the underlying molecular mechanism responsible for the ergogenic effect are unknown. Recent studies show that ginseng contains a novel ingredient, gintonin, which consists of a unique class of herbal-medicine lysophosphatidic acids (LPAs). Gintonin activates G protein-coupled LPA receptors to produce a transient [Ca(2+)]i signal, which is coupled to diverse intra- and inter-cellular signal transduction pathways that stimulate hormone or neurotransmitter release. However, relatively little is known about how gintonin-mediated cellular modulation is linked to physical endurance. In the present study, systemic administration of gintonin, but not ginsenosides, in fasted mice increased blood glucose concentrations in a dose-dependent manner. Gintonin treatment elevated blood glucose to a maximum level after 30min. This elevation in blood glucose level could be abrogated by the LPA1/3 receptor antagonist, Ki16425, or the β-adrenergic receptor antagonist, propranolol. Furthermore, gintonin-dependent enhanced performance of fasted mice in rotarod test was likewise abrogated by Ki16425. Gintonin also elevated plasma epinephrine and norepinephrine concentrations. The present study shows that gintonin mediates catecholamine release through activation of the LPA receptor and that activation of the β-adrenergic receptor is coupled to liver glycogenolysis, thereby increasing the supply of glucose and enhancing performance in the rotarod test. Thus, gintonin acts via the LPA-catecholamine-glycogenolysis axis, representing a candidate mechanism that can explain how ginseng treatment enhances physical stamina., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Concentration of blood catecholamines (CAs) is linked to a host of cardiovascular diseases, including hypertension and stenocardia. The matrix interferences and low concentration require tedious sample pretreatment methods before quantitative analysis by the gold standard method of high-performance liquid chromatography-electrochemical detector (HPLC-ECD). Solid phase extraction (SPE) has been widely used as the pretreatment technique. Here, a facile polymeric ionic liquid (PIL)-diphenylboric acid (DPBA)-packed capillary column was prepared to selectively extract dopamine (DA), noradrenaline (NE) and epinephrine (E) prior to their quantitative analysis by a fast separation in HPLC-ECD method, while microdialysis sampling method was applied to get the analysis sample. Parameters that influenced desorption efficiency, such as pH, salt concentration, acetonitrile content and wash time, were examined and optimized. The proposed method, combining microdialysis sampling technique, SPE and HPLC-ECD system, was successfully applied to detect CAs in rat blood microdialysate with high sensitivity and selectivity in small sample volumes (5-40μl) and a short analysis time (8min), yielding good reproducibility (RSD 6.5-7.7%) and spiked recovery (91-104.4%)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

High levels of circulating catecholamines have been established as fundamental pathophysiological elements of heart failure (HF). However, it is unclear whether the increased gene expression of catecholamine-synthesis enzymes in the adrenal glands contributes to these hormone abnormalities in large animal HF models. We analyzed the mRNA levels of catecholamine-synthesizing enzymes: tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AAAD), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands of 18 pigs with chronic systolic non-ischaemic HF (tachycardia-induced cardiomyopathy due to right ventricle pacing) and 6 sham-operated controls. Pigs with severe HF demonstrated an increased expression of TH and DBH (but neither AAAD nor PNMT) as compared to animals with milder HF and controls (P<0.05 in all cases). The increased adrenal mRNA expression of TH and DBH was accompanied by a reduced left ventricle ejection fraction (LVEF) (P<0.001) and an elevated plasma B-type natriuretic peptide (BNP) (P<0.01), the other indices reflecting HF severity. There was a positive relationship between the increased adrenal mRNA expression of TH and DBH, and the high levels of circulating adrenaline and noradrenaline (all P<0.05). The association with noradrenaline remained significant also when adjusted for LVEF and plasma BNP, suggesting a significant contribution of adrenals to the circulating pool of catecholamines in subjects with systolic HF.

A new microextraction by packed sorbent (MEPS) procedure coupled to a high-performance liquid chromatographic method has been developed for quantitation of catecholamines (i.e. norepinephrine, epinephrine and dopamine) in innovative biological samples, namely dried plasma and urine spots. Analyses were carried out on a C18 reversed-phase column using a mobile phase composed of 2.5% methanol and 97.5% aqueous citrate buffer, containing octanesulfonic acid. Coulometric detection was used, setting the first analytical cell at -0.350 V and the second analytical cell at +0.400 V. Dried matrices were purified by means of a fast and feasible MEPS procedure, optimized on C18 sorbent and requiring only a small amount of biological sample. The availability of miniaturized procedures allowed satisfying specific requirements that ought to be considered during pre-treatment intended for catecholamine analysis. The extraction yield values were always higher than 85% and sensitivity was good, with a limit of quantitation of 100 pg mL(-1) for all the analytes. Satisfactory results were also obtained in terms of linearity, precision and accuracy. The method was successfully applied to dried plasma and urine spots derived from two socially diversified groups, namely psychiatric patients and poly-drug abusers, in comparison to healthy volunteers., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Early intravenous epinephrine administration may help to achieve return of spontaneous circulation in cardiac arrest (CA). However, venous access can be challenging in small children. This study investigates the effect of intravenous and intramuscular epinephrine in treatment of asphyxial CA., Methods: Twenty-eight, 2-5-weeks-old, anesthetized piglets were asphyxiated by ventilation withdrawal. CA was untreated for 8 min, followed by 2 min of basic life support. Following this, epinephrine iv (10 μg·kg(-1) , group IV), epinephrine im (100 μg·kg(-1) , group IM), or normal saline (group NS) were administered. Further doses of epinephrine were given in group IV every 4 min, in group IM after 10 min if required. After twenty-two minutes of CA, iv epinephrine was given to all animals still in CA. Outcome measures were survival and epinephrine plasma concentrations., Results: Ten animals regained spontaneous circulation after 2 min of basic life support. Therefore, no drug treatment was administered (drop out). Resuscitation was effective in 2 pigs of group IM (n = 6), in 6 of group NS (n = 8) and in all of group IV (n = 4). Nonsurvivors had higher epinephrine (P < 0.01) and norepinephrine (P < 0.01) plasma concentrations prior to start of resuscitation. Median increase in epinephrine plasma concentration from T0 to T5 was 138, 134, and 29 nm in group IV, IM, and NS, respectively., Conclusions: Intravenous and intramuscular administered epinephrine led to similar increase in plasma concentrations during resuscitation of asphyxial CA without hemodynamic or survival benefit. High endogenous epinephrine and norepinephrine plasma concentrations were negative predictors for survival., (© 2014 John Wiley & Sons Ltd.)

In this study, we examined whether tooth pulp stimulation (TPS) affects the stress responses in anesthetized rats. As for stress response indices, we monitored changes in the concentrations of plasma catecholamines (CAs) (adrenaline, noradrenaline, and dopamine), corticosterone (CS), and glucose (Glu). We observed that repeated TPS attenuated plasma adrenaline, dopamine, CS, and Glu levels compared with those of sham-TPS. After administering naloxone, an opioid antagonist, repeated TPS reversed the decreases in plasma CAs, CS, and Glu. These findings showed that the effects of repeated TPS may be mediated by endogenous opioid administration. Our findings suggest that repeated TPS can induce stress-analgesia and that an endogenous descending pain modulation system exists.

We recently reported that intracerebroventricularly administered 2-arachidonoylglycerol elevated plasma noradrenaline and adrenaline by brain monoacylglycerol lipase- (MGL) and cyclooxygenase-mediated mechanisms in the rat. These results suggest that 2-arachidonoylglycerol is hydrolyzed by MGL to free arachidonic acid, which is further metabolized to prostaglandins (PGs) by cyclooxygenase in the brain, thereby elevating plasma noradrenaline and adrenaline. On the other hand, 2-arachidonoylglycerol can be also metabolized by cyclooxygenase to PG glycerol esters (PG-Gs), which seems to be hydrolyzed by MGL to free PGs. Here, we examined the involvement of brain PG-Gs in the elevation of plasma noradrenaline and adrenaline regarding PGE2-G and prostanoid EP receptors using anesthetized male Wistar rats. Intracerebroventricularly administered PGE2-G (1.5 and 3 nmol/animal) dose-dependently elevated plasma noradrenaline but not adrenaline. PGE2-G also elevated systolic, mean and diastolic blood pressure and heart rate. The PGE2-G-induced elevation of plasma noradrenaline was attenuated by JZL184 (MGL inhibitor). Intracerebroventricularly administered PGE2 (0.3 and 1.5 nmol/animal) and sulprostone (0.1 and 0.3 nmol/animal) (EP1/EP3 agonist) also elevated plasma noradrenaline but not adrenaline in a dose-dependent manner. The sulprostone-induced elevation was attenuated by L-798,106 (EP3 antagonist), but not by SC-51322 (EP1 antagonist). L-798,106 also attenuated the PGE2-G- and PGE2-induced elevation of plasma noradrenaline, while PF-04418948 (EP2 antagonist) and L-161,982 (EP4 antagonist) had no effect on the PGE2-G-induced response. These results suggest a possibility that brain PGE2-G produced from 2-arachidonoylglycerol can be hydrolyzed to free PGE2, thereby activating central sympathetic outflow by brain prostanoid EP3 receptor-mediated mechanisms in the rat., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study is to investigate potential associations between sympathoadrenal activation and/or vasopressor/inotropic therapy and endothelial activation, damage, and coagulopathy in septic patients., Materials and Methods: Septic patients included in the Scandinavian Starch for Severe Sepsis/Septic Shock trial who were expected not to receive catecholamines at screening preintervention (baseline) and had baseline blood sampled. Clinical, outcome data, and measurements of plasma concentration (p-) biomarkers reflecting sympathoadrenal activation, endothelial activation and damage, natural anticoagulation, fibrinolysis, cell damage, and platelet activation., Results: Sixty-seven patients were included, of whom 14 turned out to receive noradrenaline infusion at blood sampling. These 14 patients had p-noradrenaline 5-fold higher than patients not receiving catecholamines (n=53), whereas no other baseline preintervention biomarkers differed. In the 53 patients not receiving catecholamines at blood sampling, endogenous p-noradrenaline correlated positively with adrenaline, syndecan 1, soluble vascular endothelial growth factor receptor 1, soluble CD40 ligand, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) and negatively with PAI-1/tissue-type plasminogen activator ratio (all P<.05) and was independently associated with syndecan 1, soluble vascular endothelial growth factor receptor 1, and PAI-1 (all P<.05), and 28- and 90-day mortality (P<.05)., Conclusions: In septic patients, endogenous noradrenaline was independently associated with biomarkers of endothelial activation, damage, fibrinolysis and mortality, comparable with findings in trauma and myocardial infarction patients. The catecholamine surge in critical illness may contribute to balance endothelial damage and procoagulation with hypocoagulability and hyperfibrinolysis in the circulating blood., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To explore the possible role of the sympathetic nervous activity in the asymmetrical crosstalk between the brain and immune system, catecholamine (E, NE) plasma levels, Interferon-γ (IFN-γ) serum levels and production of antibodies induced by rabies vaccine in dogs selected for their paw preference were measured. The results showed that the direction of behavioural lateralization influenced both epinephrine levels and immune response in dogs. A different kinetic of epinephrine levels after immunization was observed in left-pawed dogs compared to both right-pawed and ambidextrous dogs. The titers of antirabies antibodies were lower in left-pawed dogs than in right-pawed and ambidextrous dogs. Similarly, the IFN-γ serum levels were lower in left-pawed dogs than in the other two groups. Taken together, these findings showed that the left-pawed group appeared to be consistently the different group stressing the fundamental role played by the sympathetic nervous system as a mechanistic basis for the crosstalk between the brain and the immune system.

The efficacy of tyrosine, a catecholamine precursor, as a countermeasure in the reduction of cognitive decline during heat exposure (HE) using event-related potential P300, and contingent negative variation (CNV) was evaluated. Ten healthy males, age 20-30years participated in the study. Volunteers received placebo or tyrosine (6.5g) 90min prior to HE (1.5h in 45°C+30% RH). P300 latency was significantly increased (p<0.01) during exposure with placebo, which was reduced significantly (p<0.01) after tyrosine supplementation. There was an increase in CNV M100 latency (p<0.05) and reaction time (p<0.01) and decrease in M100 amplitude (p<0.01) during HE with placebo, which returns to near normal level with the tyrosine administration. A significantly higher plasma norepinephrine (p<0.05), dopamine and epinephrine levels were detected in tyrosine supplemented group post heat exposure. HE increases the brain catecholamine activity thereby reduces the plasma norepinephrine and dopamine level leading to a reduction in cognitive performances. Tyrosine supplementation increases the catecholamine level and reduces the impairment of cognitive performance during HE., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The harbour porpoise is exposed to increasing pressure caused by anthropogenic activities in its marine environment. Numerous offshore wind farms are planned or under construction in the North and Baltic Seas, which will increase underwater noise during both construction and operation. A better understanding of how anthropogenic impacts affect the behaviour, health, endocrinology, immunology and physiology of the animals is thus needed. The present study compares levels of stress hormones and mRNA expression of cytokines and acute-phase proteins in blood samples of harbour porpoises exposed to different levels of stress during handling, in rehabilitation or permanent human care.Free-ranging harbour porpoises, incidentally caught in pound nets in Denmark, were compared to harbour porpoises in rehabilitation at SOS Dolfijn in Harderwijk, the Netherlands, and individuals permanently kept in human care in the Dolfinarium Harderwijk and Fjord & Belt Kerteminde, Denmark. Blood samples were investigated for catecholamines, adrenaline, noradrenaline and dopamine, as well as for adrenocorticotropic hormone (ACTH), cortisol, metanephrine and normetanephrine. mRNA expression levels of relevant cell mediators (cytokines IL-10 and TNFα, acute-phase proteins haptoglobin and C-reactive protein and the heat shock protein HSP70) were measured using real-time PCR., Results: Biomarker expression levels varied between free-ranging animals and porpoises in human care. Hormone and cytokine ranges showed correlations to each other and to the health status of investigated harbour porpoises. Hormone concentrations were higher in free-ranging harbour porpoises than in animals in human care. Adrenaline can be used as a parameter for the initial reaction to acute stress situations; noradrenaline, dopamine, ACTH and cortisol are more likely indicators for the following minutes of acute stress. There is evidence for different correlations between production of normetanephrine, metanephrine, cortisol and the expression of IL-10, HSP70 and haptoglobin., Conclusions: The expression patterns of the selected molecular biomarkers of the immune system are promising to reflect the health and immune status of the harbour porpoise under different levels of stress.

Objective: To study the influence on serum catecholamine (CA) in process of cold air activities., Methods: Residents of Zhangye City in Gansu Province were selected by means of random cluster sampling. Dopamine (DA), adrenaline (AD), norepinephrine (NE) were measured before, in the transit and after the cold air transit., Results: The DA of cases and control group have notable changes before, in and after the cold air transit, statistics test have significant difference (P < 0.05), multiple comparison have significant difference (P < 0.05) in DA changed obviously (P < 0.05) of control group. Before and mid cold air activity, the DA and NE level have the differences of case group., Conclusion: The cold air activities have the influence on catecholamine level in health people and patients. DA and NE may play the critical role in disease happening.

Positive emotional states have been reported to modify human resilience to fear and anxiety, but few animal models are available to elucidate underlying mechanisms. In the current study, we examined whether 2 weeks of tickling, which is considered to evoke positive emotions, alters conditioned fear and hormonal reactions in Fischer rats. We conditioned rats to fear an auditory tone which was initially paired with a mild foot-shock (0.2mA), and retention test was conducted 48h and 96h after conditioning. During these tests, we found that prior tickling treatment significantly diminished fear-induced freezing. To examine the effects of tickling on sympatho-adrenal and hypothalamic-pituitary-adrenal responses associated with conditioned fear, we measured plasma catecholamine and corticosterone levels in the retention test 96h after conditioning. The plasma catecholamine concentration of non-tickled rats was higher than basal levels, whereas tickled rats showed significantly reduced concentrations of both plasma adrenaline and noradrenaline. No significant differences in plasma corticosterone levels were observed between tickled and non-tickled rats. These results suggest that repeated exposure to tickling can modulate fear-related behavior and sympatho-adrenal stress responses., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The aim of this study was to retrospectively examine adrenal venous catecholamine concentrations and related indices in non-pheochromocytoma patients and to estimate from the obtained results whether measurements of adrenal venous catecholamine concentrations by adrenal venous sampling (AVS) are useful for localizing adrenal pheochromocytoma. The study population comprised 15 patients in whom AVS was performed for evaluation of adrenal non-pheochromocytoma masses (primary aldosteronism, n = 8; Cushing syndrome, n = 5; non-hyperfunctioning tumor, n = 2) without hormonal intervention and was successful in bilaterally judging adrenal vein to infra-renal inferior vena cava cortisol ratios as >3.0. Wide ranges of catecholamine concentrations were seen for both right (epinephrine, 35-175,821 pg/ml; norepinephrine, 115-32,102 pg/ml; dopamine, 9-232 pg/ml) and left (epinephrine, 16-27,251 pg/ml; norepinephrine, 155-9,267 pg/ml; dopamine, 5-234 pg/ml) adrenal veins. High- to low-side adrenal vein concentration ratios also showed wide ranges of up to 779 for epinephrine, 22.5 for norepinephrine, and 7.8 for dopamine. Adrenal venous catecholamine concentrations obtained by AVS and simple comparisons between bilateral adrenal veins might not be useful to localize adrenal pheochromocytoma, as wide variations in concentrations and high- to low-side adrenal vein concentration ratios were noted in patients with adrenal non-pheochromocytoma.

A dimeric Cu(II) complex [Cu(μ(2)-hep)(hep-H)](2)·2ClO(4) (1) containing bidentate (hep-H=2-(2-hydroxyethyl)pyridine) ligand was synthesized and characterized by single crystal X-ray diffraction studies. Each Cu-ion in 1 is in a distorted square pyramidal geometry. Further 1 along with silver nanoparticles (SNPs) have been used as modifier in the construction of a biomimetic sensor (1-SNP-GCPE) for determining certain catecholamines viz., dopamine (DA), levodopa (l-Dopa), epinephrine (EP) and norepinephrine (NE) using cyclic voltammetry, chronocoulometry, electrochemical impedance spectroscopy and adsorptive stripping square wave voltammetry (AdSSWV). Finally, the catalytic properties of the sensor were characterized by chronoamperometry. Employing AdSSWV, the calibration curves showed linear response ranging between 10(-6) and 10(-9)M for all the four analytes with detection limits (S/N=3) of 8.52×10(-10)M, 2.41×10(-9)M, 3.96×10(-10)M and 3.54×10(-10)M for DA, l-Dopa, EP and NE respectively. The lifetime of the biomimetic sensor was 3 months at room temperature. The prepared modified electrode shows several advantages such as simple preparation method, high sensitivity, high stability, ease of preparation and regeneration of the electrode surface by simple polishing along with excellent reproducibility. The method has been applied for the selective and precise analysis of DA, l-Dopa, EP and NE in pharmaceutical formulations, urine and blood serum samples., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Neurogenic pulmonary edema (NPE) occurs frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been suggested as its principal cause. The objective of this retrospective study is to evaluate the relative contribution of each catecholamine in the pathogenesis of NPE associated with SAH., Methods: Records of 63 SAH patients (20 men/43 women) whose plasma catecholamine levels were measured within 48 h of SAH onset were reviewed, and the clinical characteristics and laboratory data of those who developed early-onset NPE were analyzed thoroughly., Results: Seven patients (11 %) were diagnosed with NPE on admission. Demographic comparison revealed that the NPE+ group sustained more severe SAH than the NPE- group. Cardiac dysfunction was also significantly more profound in the former, and the great majority of the NPE+ group sustained concomitant cardiac wall motion abnormality. There was no significant difference in the plasma epinephrine levels between NPE+ and NPE- group (324.6 ± 172.8 vs 163.1 ± 257.2 pg/ml, p = 0.11). By contrast, plasma norepinephrine levels were significantly higher in the NPE+ group (2977.6 ± 2034.5 vs 847.9 ± 535.6 pg/ml, p < 0.001). Multivariate regression analysis revealed that increased norepinephrine levels were associated with NPE (OR, 1.003; 95 % CI, 1.002-1.007). Plasma epinephrine and norepinephrine levels were positively correlated (R = 0.48, p < 0.001). According to receiver operating characteristic curve analysis, the threshold value for plasma norepinephrine predictive of NPE was 2,000 pg/ml, with an area under the curve value of 0.85., Conclusions: Elevated plasma norepinephrine may have more active role in the pathogenesis of SAH-induced NPE compared with epinephrine, although both catecholamines may be involved via multiple signaling pathways.

Objective:   Electrical stimulation of the vagus nerve at relatively high voltages (e.g., >10 V) can induce bronchoconstriction. However, low voltage (≤2 V) vagus nerve stimulation (VNS) can attenuate histamine-invoked bronchoconstriction. Here, we identify the mechanism for this inhibition., Methods:   In urethanea-nesthetized guinea pigs, bipolar electrodes were attached to both vagus nerves and changes in pulmonary inflation pressure were recorded in response to i.v. histamine and during VNS. The attenuation of the histamine response by low-voltage VNS was then examined in the presence of pharmacologic inhibitors or nerve ligation., Results:   Low-voltage VNS attenuated histamine-induced bronchoconstriction (4.4 ± 0.3 vs. 3.2 ± 0.2 cm H(2) O, p < 0.01) and remained effective following administration of a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, and after sympathetic nerve depletion with guanethidine, but not after the β-adrenoceptor antagonist propranolol. Nerve ligation caudal to the electrodes did not block the inhibition but cephalic nerve ligation did. Low-voltage VNS increased circulating epinephrine and norepinephrine without but not with cephalic nerve ligation., Conclusion:   These results indicate that low-voltage VNS attenuates histamine-induced bronchoconstriction via activation of afferent nerves, resulting in a systemic increase in catecholamines likely arising from the adrenal medulla., (© 2012 International Neuromodulation Society.)

SULT1A enzymes protect humans from catecholamines, but natural substances in many foods have been found to inhibit these enzymes in vitro. Given the hormonal roles of catecholamines, any in vivo SULT1A inhibition could have serious consequences. This paper uses a re-analysis of published data to confirm that SULT1A inhibitors have effect in vivo in at least some patients. Nineteen studies are cited that show ingestion of SULT1A inhibitors leading to catecholamine increases, blood pressure changes, migraine headaches, or atrial fibrillation. SULT1A inhibition does not create the catecholamines, but prevents normal catecholamine deactivation. Susceptible patients probably have lower-activity SULT1A alleles. The paper discusses new hypotheses that SULT1A inhibition can cause "holiday heart" arrhythmias and type 2 diabetes in susceptible patients. Subgroup analysis based on SULT1A alleles, and addition of a catecholamine source, should improve the consistency of results from tests of SULT1A inhibitors. SULT1A inhibition may be a key contributor to cheese-induced migraines (via annatto), false positives in metanephrine testing, and the cardiovascular impacts of recreational alcohols., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: This study examined the effects of Palm vitamin E (PVE) and α-tocopherol (α-TF) supplementations on adrenalin, noradrenalin, xanthine oxidase plus dehydrogenase (XO + XD) activities and gastric lesions in rats exposed to water-immersion restraint stress (WIRS)., Methods: Sixty male Sprague-Dawley rats (200-250 g) were randomly divided into three equal sized groups. The control group was given a normal diet, while the treated groups received the same diet with oral supplementation of PVE or α-TF at 60 mg/kg body weight. After the treatment period of 28 days, each group was further subdivided into two groups with 10 rats without exposing them to stress and the other 10 rats were subjected to WIRS for 3.5 hours. Blood samples were taken to measure the adrenalin and noradrenalin levels. The rats were then sacrificed following which the stomach was excised and opened along the greater curvature and examined for lesions and XO + XD activities., Results: The rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementations of PVE and α-TF were able to reduce gastric lesions significantly in comparison to the stressed control group. WIRS increased plasma adrenalin and noradrenalin significantly. PVE and α-TF treatments reduced these parameters significantly compared to the stressed control., Conclusions: Supplementations with either PVE or α-TF reduce the formation of gastric lesions. Their protective effect was related to their abilities to inhibit stress induced elevation of adrenalin and noradrenalin levels as well as through reduction in xanthine oxidase and dehydrogenase activities.

Catecholamines (CAs), namely adrenaline (A), noradrenaline (NA), and dopamine (DA), are secreted by the sympathoadrenal system and participate in a diverse array of functions, e.g., heat production, cardiovascular regulation, stress response and so on. However, little is known regarding peripheral CA fluctuations in cetaceans; nevertheless aquatic animals like them have needed to modify their physiological response especially for thermoregulation in water and oxygen economy during diving. To understand CA dynamism in cetaceans, diurnal changes in serum A, NA, and DA concentrations were measured during the winter and summer solstices in four Indo-Pacific bottlenose dolphins (Tursiops aduncus). The average serum NA concentration was much higher than the average A and DA concentrations, and all concentrations were higher than those reported in other cetacean species. No distinct diurnal fluctuations were observed in CA concentrations in either solstice, suggesting inhibition of the decrease in CA concentrations during nocturnal periods by the unique sleep pattern of dolphins. All the serum CA concentrations were negatively correlated with water temperature as body temperatures were, indicating that the sympathoadrenal system might be more active during winter than in summer season, suggesting a role of CA in thermoregulation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To examine the hypothesis that genetic variation in enzymes and transporters associated with synthesis, storage, release, and metabolism of catecholamines contributes to the interindividual variability in plasma catecholamine concentrations at rest and after exercise., Methods: We measured plasma norepinephrine (NE) and epinephrine concentrations at rest and after a standardized exercise protocol in 165 healthy individuals (60% White, 40% African-American) and examined 29 functional or common variants in 14 genes involved in synthesis, transport, or metabolism of catecholamines. We examined the relationship between genotypes and NE concentrations at rest and the increase after exercise (ΔNE) by multiple linear regression with adjustment for covariates [age, race, sex, BMI, fitness, and resting NE (for ΔNE)]. As a secondary outcome, we carried out similar analyses for epinephrine concentrations., Results: There was large interindividual variability in resting NE (mean, 204±102 pg/ml; range, 39-616 pg/ml) and ΔNE (mean, 256±206 pg/ml; range, -97 to 953 pg/ml). Resting NE was significantly associated with variants of four genes: CYB561 (P<0.001), VMAT2 (P=0.016), CHGA (P=0.039), and PNMT (P=0.038). ΔNE after exercise was associated with three variants of PNMT (P=0.041) and COMT (P=0.033 and 0.035), and resting and exercise epinephrine concentrations were associated with two variants each., Conclusion: The findings of this exploratory study suggest that variation in catecholamine pathway genes contributes to the interindividual variability in plasma NE and epinephrine concentrations at rest and after exercise.

Postoperative pain is often stated to be a significant contributor to a sympathetic stress response after surgery. However, hardly any evidence has been published to support this assumption. Hence it was the aim of this trial to investigate the relationship between postoperative pain and hemodynamic, endocrine, and autonomic parameters. A total of 85 postoperative patients in the recovery room were repeatedly asked to rate their pain on a numeric rating scale (NRS). Concurrently, the parameters of heart rate variability (HRV) were analysed, and mean arterial pressure (MAP), heart rate (HR) and respiration rate (RR) were recorded. Pain was categorized into no, mild, moderate, and severe. Blood samples were taken for epinephrine (EPI) and norepinephrine (NE) plasma level assessment at the time of recovery room admission and discharge, and each time pain was found decreased in categorized severity. A total of 239 pain readings were obtained. None of the investigated parameters correlated with NRS scores. NE was higher at NRS 5 to 10 vs. NRS 0 to 4 (mean [SEM]: 1009 [73] pg/mL vs. 872 [65] pg/mL; P<0.01). This was also found for MAP, but not for EPI or the parameters of HRV, HR, and RR. In contrast to common belief, the severity of postoperative pain does not appear to be associated with the degree of sympathetic stress response after surgery, and other factors such as surgical trauma may be more important. Importantly, the absence of signs of sympathetic stimulation cannot be seen as a guarantee for the absence of significant pain., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Aim: Carotid artery stenting (CAS) may cause bradycardia and hypotension due to barostimulation. The impact of periprocedural hypotension on CAS outcome remains controversial. The role of carotid plaque volume and catecholamine hormone release during CAS on hemodynamic changes has not been investigated so far. The aim of this prospective study was to evaluate if carotid artery plaque characteristics are predictive for stress hormone release or for postprocedural hemodynamic instability., Methods: In 26 patients undergoing CAS, carotid plaque volume and morphology were assessed by two- and three-dimensional (3D)-Duplex sonography prior to the procedure. Arterial plasma adrenaline, noradrenaline and renin concentrations were measured at the time of sheath insertion and 5 minutes after stent placement. ECG, heart rate, and invasive blood pressure were monitored throughout the procedure., Results: CAS caused no significant changes in hormone release, but increasing plaque volume was related to the degree of bradycardia following stent deployment (r=0.57; P=0.01). Plaque size was not associated with postprocedural hypotension. Plaque echogenicity (echolucent, heterogeneous or echogenic) did not correlate with changes in systolic blood pressure, heart rate or catecholamine hormone release., Conclusion: CAS caused bradycardia in relation to plaque size, but did not cause catecholamine release which may indicate that the endovascular procedure is not associated with a relevant stress reaction.

Acute temperature stress in animals results in increases in heat shock proteins (HSPs) and stress hormones. There is evidence that stress hormones influence the magnitude of the heat shock response; however, their role is equivocal. To determine whether and how stress hormones may affect the heat shock response, we capitalized on two lines of rainbow trout specifically bred for their high (HR) and low (LR) cortisol response to stress. We predicted that LR fish, with a low cortisol but high catecholamine response to stress, would induce higher levels of HSPs after acute heat stress than HR trout. We found that HR fish have significantly higher increases in both catecholamines and cortisol compared with LR fish, and LR fish had no appreciable stress hormone response to heat shock. This unexpected finding prevented further interpretation of the hormonal modulation of the heat shock response but provided insight into stress-coping styles and environmental stress. HR fish also had a significantly greater and faster heat shock response and less oxidative protein damage than LR fish. Despite these clear differences in the physiological and cellular responses to heat shock, there were no differences in the thermal tolerance of HR and LR fish. Our results support the hypothesis that responsiveness to environmental change underpins the physiological differences in stress-coping styles. Here, we demonstrate that the heat shock response is a distinguishing feature of the HR and LR lines and suggest that it may have been coselected with the hormonal responses to stress.

Children with Asperger and Kanner syndromes in the stable state demonstrate similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine and by an increase in dopamine and homovanylic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanylic acid, epinephrine and MHPG. Only in children with Kanner syndrome in the aggravated state plasma MHPG increases, excretion of tyrosine decreases and excretion of normetanephrine increases. The observed imbalance in dopamine and epinephrine/norepinephrine systems justifies combined analysis of changes in catecholamines and their metabolites levels as the most informative approach in the study of the effect of autistic disorders.

Objective: The objective of this study was to evaluate the effect of intravenous lidocaine combined with amitriptyline on pain relief and plasma serotonin, norepinephrine, and dopamine levels., Methods: A prospective, randomized, double-blind comparative study was conducted in 30 patients. All patients received 25 mg amitriptyline; monotherapy group (n=15) received 125 mL saline, and combined therapy group (n=15) received 240 mg lidocaine in 125 mL saline once a week for 4 weeks. Serotonin, norepinephrine, and dopamine were measured in plasma at time zero (T0) and after 4 weeks (T4). Pain intensity was rated on a numerical scale at the beginning of the study and weekly for 4 weeks., Results: All patients were females and the mean age was 44.7±10.5 years for monotherapy group and 40.9±11.6 years for combined therapy group. No difference in pain intensity at baseline was observed between groups, with a decrease after treatment in monotherapy group (T0: 7.0±1.2 and T4: 4.0±2.1) and in combined therapy group (T0: 7.6±0.8 and T4: 4.1±2.3). Plasma serotonin and norepinephrine levels were similar in the 2 groups at T0 and T4. An increase in dopamine levels was observed in monotherapy group from the beginning to the end of treatment., Conclusions: Combined administration of 240 mg intravenous lidocaine (once a week) and 25 mg amitriptyline for 4 weeks did not modify pain intensity or plasma serotonin, norepinephrine, or dopamine concentrations in fibromyalgia patients.

Aims: MicroRNAs (miRNAs) are small non-coding RNAs discovered as potential new gene regulators. Their roles in the development of chronic heart failure (CHF), however, are largely unknown. Reduced catecholamine sensitivity is an early step of CHF. We examined whether altered expression of miRNAs was related to reduced catecholamine sensitivity in patients with CHF., Methods and Results: Maximum first derivative of left ventricular pressure (LV dP/dt(max)) at baseline and during infusion of dobutamine (10 μg kg(-1)min(-1)) were determined in 14 asymptomatic or mildly symptomatic (New York Heart Association class I or II) patients with idiopathic dilated cardiomyopathy (DCM). We performed microarray analysis for a total of 485 miRNAs using endomyocardial biopsy specimens from these 14 patients. Patients were classified into 2 groups based on a percent increase in LV dP/dt(max) by dobutamine infusion (ΔLV dP/dt(max)). These are Group I (n=7) with ΔLV dP/dt(max)>90%, and Group II (n=7) with ΔLV dP/dt(max)<90%. Out of 485 miRNAs, 32 were differentially expressed in the myocardium with reduced catecholamine sensitivity. Among those, four miRNAs were decreased and one miRNA was increased in the Group II compared to the Group I (p<0.01). LVEF measured by left ventriculography at baseline did not differ between the 2 groups. Also there were no differences in plasma norepinephrine levels between the 2 groups., Conclusions: Altered expression of several miRNAs was related to the reduced catecholamine sensitivity in mildly symptomatic patients with DCM. These findings shed light on the potential of miRNAs to provide possible etiologic insights as well as therapeutic targets for CHF., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)