Plasma Catecholamine Concentrations Research Articles

Effects of repeated tickling on conditioned fear and hormonal responses in socially isolated rats

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.

Die Diagnose des Phäochromozytoms und Paraganglioms

Measurements of plasma free metanephrines provide a sensitive test for the diagnosis of pheochromocytoma/paraganglioma (P/PGL), with highly elevated levels diagnostic of the disease. However, there is less diagnostic certainty in patients with mild elevations of these catecholamine metabolites. Here we report use of the clonidine suppression test (CST) as a second-tier diagnostic test in 24 patients with mild elevations of plasma free metanephrines and/or catecholamines. Blood samples before and 3 hours after clonidine were analyzed for plasma concentrations of metanephrines and catecholamines with a negative test result defined as either a clonidine-induced fall in normetanephrine or noradrenaline by more than 40 % and 50 % respectively or to below the upper cut-offs of reference intervals. P/PGLs were confirmed in 9 patients and excluded in 15 by independent criteria. More than half of the patients without P/PGL showed normalized plasma concentrations of normetanephrine at baseline before clonidine compared to initial screening; all showed appropriate clonidine-induced falls in normetanephrine and noradrenaline or levels after the drug below upper cut-offs, indicating a diagnostic specificity of 100 % (CI 78-100 %). However, similar responses for noradrenaline were noted in 7 patients with P/PGL, indicating a diagnostic sensitivity of only 22 % (CI 2,8-60 %) compared to 100 % (CI 66-100 %) for normetanephrine. These results support use of the CST in combination with measurements of normetanephrine for confirming or excluding P/PGL in patients with borderline elevated test results, which should, however, first be confirmed by sampling blood under standardized resting conditions.

The Effects of Sports Drink Osmolality on Fluid Intake and Immunoendocrine Responses to Cycling in Hot Conditions

We investigated the effects of two carbohydrate-based sports drinks on fluid intake and immunoendocrine responses to cycling. Six well-trained male cyclists completed trials on three separate days that involved cycling at 60% VO(2peak) for 90 min in hot conditions (28.1 ± 1.5ºC and 52.6 ± 3.1% relative humidity). During each trial, the subjects consumed ad libitum (1) an isotonic sports drink (osmolality 317 mOsm/kg), (2) a hypotonic sports drink (osmolality 193 mOsm/kg) or (3) plain water. The cyclists consumed significantly (p<0.05) more of the isotonic drink (1.23 ± 0.35 L) and hypotonic drink (1.44 ± 0.55 L) compared with water (0.73 ± 0.26 L). Compared with water (-0.96 ± 0.26 kg), body mass decreased significantly less after consuming the hypotonic drink (-0.50 ± 0.38 kg) but not the isotonic drink (-0.51 ± 0.41 kg). Blood glucose concentration was significantly higher at the end of the isotonic and hypotonic drink trials compared with the water trial. Neutrophil count and the plasma concentrations of catecholamines, interleukin 6 (IL-6), myeloperoxidase, calprotectin and myoglobin increased significantly during all three trials. IL-6 and calprotectin were significantly lower following the hypotonic drink trial compared with the water trial. In conclusion, hypotonic sports drinks are appealing for athletes to drink during exercise, and may help to offset fluid losses and attenuate some inflammatory responses to exercise.

Tyramine Reveals Failing α2-Adrenoceptor Control of Catecholamine Release and Total Peripheral Vascular Resistance in Hypertensive Rats

α2-Adrenoceptor-activation lowers central sympathetic output, peripheral, vesicular norepinephrine release, epinephrine secretion, and modulates vascular tension. We previously demonstrated that α2-adrenoceptor-mediated inhibition of basal norepinephrine release was not reflected in plasma unless re-uptake through the norepinephrine transporter (NET) was blocked. Tyramine activates reverse norepinephrine transport through NET. Here we tested the hypothesis that tyramine, by engaging NET in release, also blocks re-uptake, and therefore allows manipulation of pre-junctional α2-adrenoceptors to directly regulate norepinephrine overflow to plasma. We compared in anesthetized spontaneously hypertensive rats (SHRs) and normotensive controls (WKYs), the effect of α2-adrenoreceptor antagonist (L-659,066) and/or agonist (clonidine) on norepinephrine overflow and increase in total peripheral vascular resistance (TPR) evoked by tyramine-infusion (1.26 μmol/min/kg, 15 min) and epinephrine secretion activated by the surgical stress. TPR was computed as blood pressure divided by cardiac output, recorded as ascending aortic flow. Plasma catecholamine concentrations after tyramine were higher in SHRs than WKYs. Pre-treatment with L-659,066 increased the catecholamine concentrations in WKYs, but only if combined with clonidine in SHRs. Clonidine alone reduced tyramine-induced norepinephrine overflow in SHRs, and epinephrine in both strains. Tyramine-induced increase in TPR was not different after clonidine, eliminated after L-659,066 and L-659,066 + clonidine in WKYs, but only after L-659,066 + clonidine in SHRs. We conclude that tyramine-infusion does allow presynaptic regulation of vesicular release to be accurately assessed by measuring differences in plasma norepinephrine concentration. Our results indicate that presynaptic α2-adrenoceptor regulation of norepinephrine release from nerve vesicles and epinephrine secretion is dysfunctional in SHRs, but can be restored by clonidine.

Regional Sympathetic Blockade Attenuates Activation of Intestinal Macrophages and Reduces Gut Barrier Failure

Endotoxin-induced activation of monocytes may lead to extravasation of cells, excessive production of nitric oxide, and subsequent epithelial injury in the gut. Regional sympathetic blockade by means of thoracic epidural anesthesia has been implicated to protect the epithelial barrier. This study tested the hypothesis that thoracic epidural anesthesia decreases epithelial permeability by attenuating monocytic production of nitric oxide and nitrosative stress. Rats were anesthetized, hemodynamically monitored, and mechanically ventilated. Endotoxemia was induced by an intravenous bolus injection of Escherichia coli lipopolysaccharide. Either lidocaine 2% or normal saline was injected as a bolus, followed by a continuous infusion via an epidural catheter. Three hundred minutes after injection of lipopolysaccharide or normal saline, gut epithelial permeability to fluorescein isothiocyanate-dextran (4 kDa), intestinal expression of inducible nitric oxide synthase by macrophages, and lipid peroxidation represented by 8-isoprostane tissue concentration were quantified. Thoracic epidural anesthesia significantly attenuated the endotoxin-induced increases in gut epithelial permeability (437 [293, 492] vs. 628 [532, 1,042] ng/ml, median [quartiles], P = 0.03), expression of nitric oxide synthase (2 [1,2] vs. 7 [5,8] cells per 384 µm(2), P = 0.003), macrophage infiltration, and lipid peroxidation (22,460 ± 11,476 vs. 37,840 ± 17,551 pg/ml, mean ± SD, P = 0.05). Thoracic epidural anesthesia attenuates endotoxin-induced gut epithelial injury. This is likely due to a decrease in monocytic extravasation and intestinal nitrosative stress. As possible mechanisms, direct nerve-immune interplay, a reduction in plasma catecholamines, or a systemic lidocaine effect has to be considered.

Xenon: A Solution for Anesthesia in Liver Disease?

Xenon: A Solution for Anesthesia in Liver Disease?

A dose–response study of remifentanil for attenuation of the hypertensive response to laryngoscopy and tracheal intubation in severely preeclamptic women undergoing caesarean delivery under general anaesthesia

BackgroundRemifentanil is known to attenuate the cardiovascular responses to tracheal intubation. We determined effective doses (ED50/ED95) of remifentanil to prevent the pressor response to tracheal intubation in patients with severe preeclampsia. MethodsSeventy-five women with severe preeclampsia were randomly allocated to one of five remifentanil dose groups (0.25, 0.50, 0.75, 1.0, or 1.25μg/kg) given before induction of anaesthesia using thiopental 5mg/kg and suxamethonium 1.5mg/kg. Systolic arterial pressure, heart rate and plasma catecholamine concentrations were measured. Neonatal effects were assessed by Apgar scores and umbilical cord blood gas analysis. A dose was considered effective when systolic arterial pressure did not exceed 160mmHg for more than 1min following tracheal intubation. ResultsBaseline systolic blood pressure and heart rate did not differ among the groups. The intubation-induced increases of heart rate and blood pressure were attenuated in a dose-dependent manner by remifentanil. ED50 and ED95 were 0.59 (95% CI 0.47–0.70)μg/kg and 1.34 (1.04–2.19)μg/kg, respectively. Norepinephrine concentrations remained unaltered following intubation but increased significantly at delivery, with no differences between the groups. Apgar scores and umbilical arterial and venous pH and blood gas values were comparable among the groups. Two women each in the 1.0 and 1.25μg/kg groups received ephedrine for hypotension defined as systolic arterial pressure <90mmHg. ConclusionsThe ED95 of remifentanil for attenuating the hypertensive response to tracheal intubation during induction of anaesthesia in severely preeclamptic patients undergoing caesarean delivery under general anaesthesia was 1.34μg/kg.

Restraint Stress Restrains Cholesterol in the Intestine

Epidemiological studies have observed that psychosocial stress, for example, by unemployment, low socioeconomic status, or work stress, increases the risk of cardiovascular events.1 The pathophysiological basis of this association is poorly understood. Restraint stress, which is an experimental model for psychosocial stress, is characterized by the activation of the sympathetic nervous system involving the fast release of epinephrine and norepinephrine and the hypothalamic-pituitary-adrenal axis, resulting in a slow but sustained increase in circulating glucocorticoids.2 Both neuroendocrine axes elicit multiple and complex responses, aiming to protect the threatened organism. As yet, there is little and mixed epidemiological evidence about which of these pathways is relevant for the pathogenesis of cardiovascular diseases.3–6 Diurnal and other intraindividual variation of cortisol and catecholamine plasma concentrations make the design of meaningful observational studies difficult. More recently, measurements of cortisol in saliva or urine found positive associations between cortisol and risk of incident coronary events.5,6 Elevated cortisol levels in plasma or saliva have also been associated with increased blood pressure, diabetes mellitus, hyperglycemia, hypertriglyceridemia, and central adiposity. However, these associations have been questioned by 2 recent population studies that did not find any significant association of cortisol awakening response, evening cortisol, cortisol decline across the waking day, total cortisol output, and cortisol after dexamethasone suppression with metabolic syndrome or its individual components.7,8 Article, see p 1459 In addition to their importance of mobilizing stored energy and maintaining vascular tone during stress, glucocorticoids limit their own production by negative feedback inhibition, primarily via inhibiting the hypothalamic release of cortisol-releasing factor and the release of adrenocorticotropic hormone in the pituitary gland.2 Because cholesterol is a precursor of steroidogenesis, regulation of cholesterol metabolism is another potential target of glucocorticoid release in psychosocial stress. In this issue of …

Effects of propiverine hydrochloride, an anticholinergic agent, on urethral continence mechanisms and plasma catecholamine concentration in rats

Anticholinergics are used to treat overactive bladder. Anticholinergic agents such as propiverine hydrochloride reportedly increase plasma catecholamine levels in rats. It is also known that active urethral closure mechanisms prevents stress urinary incontinence (SUI), which is enhanced by central and peripheral noradrenergic system activation. Therefore, we examined the influence of propiverine hydrochloride on urethral anti-incontinence function in rats. Adult female rats were divided into propiverine and vehicle-treated groups. The propiverine group was given propiverine orally once a day for 2 weeks, after which urethral function and plasma concentrations of catecholamine (dopamine, norepinephrine, epinephrine) were tested. Urethral baseline pressure measured by a microtransducer-tipped urethral catheter and leak-point pressure during passive intravesical pressure elevation were significantly increased in the propiverine group compared with the vehicle group. Plasma norepinephrine and epinephrine levels in the propiverine group were also significantly increased. Propiverine treatment that increases plasma catecholamine levels could contribute to improvement of SUI conditions by increasing urethral resistance.

Abstract 57: Therapeutic Effects of Small Molecule Gβγ Inhibition in Pressure Overload Heart Failure

Heart failure (HF) is a progressive disease with rapidly increasing rates of morbidity and mortality; it is the leading cause of death worldwide. Elevated sympathetic nervous system activity, a salient feature of HF progression, leads to pathologic attenuation and desensitization of β-adrenergic receptors (β-ARs) due in part to Gβγ-mediated signaling. We recently reported that novel small molecule Gβγ inhibitors selectively block specific Gβγ signals and halt HF progression in pharmacologic and transgenic mouse models of HF. We assessed the hypothesis that the Gβγ inhibitor Gallein could be salutary in treating pre-existing HF in a clinically relevant model. We utilized the pressure-overload HF model of mouse transverse aortic constriction (TAC). Four weeks post-TAC, mice received daily IP injections of vehicle (PBS; group V) or Gallein (10mg/Kg/day; group G) for eight weeks. Gallein treatment improved survival (7 of 9 mice survived vs. 5 of 9 mice in group V) and cardiac function (%EF 75.2 ± 7.5 vs 35.6 ± 17.2 in group V, +dP/dt (mmHg/sec) 7022 ± 485.3 vs. 3584 ± 598.6 in group V), -dP/dt (mmHg/sec) -5826 ± 910.7 vs. -3260 ± 62.3 in group V, LVEDP (mmHg) 11.5 ± 3.7 vs. 29.45 ± 3.6 in group V). In addition, gallein reduced cardiac hypertrophy (HW/BW (mg/g) 5.8 ± 0.3 vs. 8.8 ± 1.1 in group V) and plasma catecholamine concentrations (adrenaline (ng/ml) 1.3 ± 0.3 vs. 6.6 ± 2.8 in group V, noradrenaline (ng/ml) 3.6 ± 0.6 vs. 15.1 ± 3.6 in group V). Reduction of interstitial fibrosis as well as mRNA levels of α-SMA, TNF-α, and IL-6 was observed in the hearts of Gallein treated animals (59.7 ± 14.1%, 43.8 ± 9.3% and 28.5 ± 3.5% relative to group V, respectively). On the molecular level, Gallein treated mice showed less GRK2 and PI3Kγ membrane recruitment, and less Akt activation (42.9 ± 7.1%, 66.7 ± 13.3% and 46.2 ± 7.7% relative to group V, respectively) in myocardial lysates. In conclusion , these data suggest a possible therapeutic role for small molecule Gβγ inhibition in halting the progression of HF, potentially via inhibition of the Gβγ-GRK2-PI3Kγ-Akt pathway. The combined effect of halting HF progression and reducing plasma catecholamines suggests a possible systemic role for small molecule Gβγ inhibition in both the heart and the adrenal gland.

Forced exercise changes catecholamine synthesis in the spleen of adult rats

Treadmill training produces modulation of neuro-endocrine and immune functions. This study examined the effects of chronic forced running (CFR) on the plasma concentration of catecholamines and the expression of splenic catecholamine biosynthetic enzymes in rats by using real-time RT-PCR and Western blot analyses. We found that CFR increases the plasma catecholamine levels, decreases splenic tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) mRNA levels and increases splenic PNMT protein levels. This shows that CFR is a very strong stressor which activates the sympatho-adrenomedullary system and increases synthesis of splenic PNMT by 20%, which both can modulate the immune function.

Catecholamine pathway gene variation is associated with norepinephrine and epinephrine concentrations at rest and after exercise.

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. 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. 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. 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.

Epinephrine opens intrapulmonary arteriovenous anastomoses in healthy humans at rest

During exercise or while breathing hypoxic gas mixtures large diameter intrapulmonary arteriovenous anastomoses (IPAVA) open and can be detected with saline contrast echocardiography (SCE). The mechanisms regulating these vessels remain unknown, but both of these conditions activate the sympathetic nervous system and increase plasma catecholamine concentrations. We hypothesized that exogenously increasing the plasma epinephrine concentration would open IPAVA. Using SCE, we studied 5 subjects at rest, before and after continuous infusions of epinephrine at 20, 40, 80, 160, and 320 ng/kg/min for 3 min each. Cardiac output (Q) and pulmonary artery systolic pressure (PASP) were measured using ultrasound. Bubble scores (0–5) increased in a dose‐dependent fashion in all subjects to a max score ranging from 2–4. Q and PASP doubled at the highest infusion rate. After a 30 min break, epinephrine infusions were repeated while subjects breathed 100% O2 and bubble scores did not increase despite similar increases in cardiac output and PASP. These data demonstrate that during exercise or when breathing hypoxic gas mixtures the sympathetically‐mediated release of epinephrine may directly open IPAVA independent of changes in cardiac output or PASP. Mechanisms responsible for hyperoxia‐mediated closure remain elusive.Support: Eugene Evonuk Graduate Fellowship in Exercise &amp; Environmental Physiology

Early adrenaline administration does not improve circulatory recovery during resuscitation from severe asphyxia in newborn piglets

Aim of the studyTo investigate the effects of early intravenous adrenaline administration on circulatory recovery, cerebral reoxygenation, and plasma catecholamine concentrations, after severe asphyxia-induced bradycardia and hypotension. MethodsOne-day-old piglets were left in apnoea until heart rate and mean arterial pressure were less than 50min−1 and 25mmHg, respectively. They randomly received adrenaline, 10μgkg−1 (n=16) or placebo (n=15) and were resuscitated with air ventilation and, when needed, closed-chest cardiac massage (CCCM). Eight not asphyxiated animals served as time controls. ResultsCCCM was required in 13 piglets given adrenaline and in 13 given placebo. Time to return of spontaneous circulation was: 72 (66–85)s vs. 77 (64–178)s [median (quartile range)] (p=0.35). Time until cerebral regional oxygen saturation (CrSO2) had increased to 30% was 86 (79–152)s vs. 126 (88–309)s (p=0.30). The two groups did not differ significantly in CrSO2, heart rate, arterial pressure, right common carotid artery blood flow, or number of survivors: 13 vs. 11 animals. Plasma concentration of adrenaline, 2.5min after resuming ventilation, was 498 (268–868)nmoll−1vs. 114 (80–306)nmoll−1 (p=0.01). Corresponding noradrenaline concentrations were 1799 (1058–4182)nmoll−1vs. 1385 (696–3118)nmoll−1 (ns). In the time controls, the concentrations were 0.4 (0.2–0.6)nmoll−1 of adrenaline and 1.8 (1.3–2.4)nmoll−1 of noradrenaline. ConclusionThe high endogenous catecholamine levels, especially those of noradrenaline, may explain why early administered adrenaline did not significantly improve resuscitation outcome.

Low-Dose Caffeine Administered in Chewing Gum Does Not Enhance Cycling to Exhaustion

Low-dose caffeine administered in chewing gum does not enhance cycling to exhaustion. The purpose of the current investigation was to examine the effect of low-dose caffeine (CAF) administered in chewing gum at 3 different time points during submaximal cycling exercise to exhaustion. Eight college-aged (26 ± 4 years), physically active (45.5 ± 5.7 ml·kg(-1)·min(-1)) volunteers participated in 4 experimental trials. Two pieces of caffeinated chewing gum (100 mg per piece, total quantity of 200 mg) were administered in a double-blind manner at 1 of 3 time points (-35, -5, and +15 minutes) with placebo at the other 2 points and at all 3 points in the control trial. The participants cycled at 85% of maximal oxygen consumption until volitional fatigue and time to exhaustion (TTE) were recorded in minutes. Venous blood samples were obtained at -40, -10, and immediately postexercise and analyzed for serum-free fatty acid and plasma catecholamine concentrations. Oxygen consumption, respiratory exchange ratio, heart rate, glucose, lactate, ratings of perceived exertion, and perceived leg pain measures were obtained at baseline and every 10 minutes during cycling. The results showed that there were no significant differences between the trials for any of the parameters measured including TTE. These findings suggest that low-dose CAF administered in chewing gum has no effect on TTE during cycling in recreational athletes and is, therefore, not recommended.

Heat Stress and Cardiovascular, Hormonal, and Heat Shock Proteins in Humans

Conditions such as osteoarthritis, obesity, and spinal cord injury limit the ability of patients to exercise, preventing them from experiencing many well-documented physiologic stressors. Recent evidence indicates that some of these stressors might derive from exercise-induced body temperature increases. To determine whether whole-body heat stress without exercise triggers cardiovascular, hormonal, and extracellular protein responses of exercise. Randomized controlled trial. University research laboratory. Twenty-five young, healthy adults (13 men, 12 women; age = 22.1 ± 2.4 years, height = 175.2 ± 11.6 cm, mass = 69.4 ± 14.8 kg, body mass index = 22.6 ± 4.0) volunteered. Participants sat in a heat stress chamber with heat (73°C) and without heat (26°C) stress for 30 minutes on separate days. We obtained blood samples from a subset of 13 participants (7 men, 6 women) before and after exposure to heat stress. Extracellular heat shock protein (HSP72) and catecholamine plasma concentration, heart rate, blood pressure, and heat perception. After 30 minutes of heat stress, body temperature measured via rectal sensor increased by 0.8°C. Heart rate increased linearly to 131.4 ± 22.4 beats per minute (F₆,₂₄ = 186, P < .001) and systolic and diastolic blood pressure decreased by 16 mm Hg (F₆,₂₄ = 10.1, P < .001) and 5 mm Hg (F₆,₂₄ = 5.4, P < .001), respectively. Norepinephrine (F₁,₁₂ = 12.1, P = .004) and prolactin (F₁,₁₂ = 30.2, P < .001) increased in the plasma (58% and 285%, respectively) (P < .05). The HSP72 (F₁,₁₂ = 44.7, P < .001) level increased with heat stress by 48.7% ± 53.9%. No cardiovascular or blood variables showed changes during the control trials (quiet sitting in the heat chamber with no heat stress), resulting in differences between heat and control trials. We found that whole-body heat stress triggers some of the physiologic responses observed with exercise. Future studies are necessary to investigate whether carefully prescribed heat stress constitutes a method to augment or supplement exercise.

Short-Term Effects of Manipulation to the Upper Thoracic Spine of Asymptomatic Subjects on Plasma Concentrations of Epinephrine and Norepinephrine—A Randomized and Controlled Observational Study

ObjectiveThe purpose of this study was to investigate the short-term effects of spinal manipulation applied to a hypomobile segment of the upper thoracic spine (T1-T6), on plasma concentrations of norepinephrine (NE) and epinephrine (E) in asymptomatic subjects, under strictly controlled conditions. MethodsFifty-six asymptomatic subjects were randomly assigned to receive either a chiropractic manipulative intervention or a sham intervention in the upper thoracic spine. A 20-gauge catheter fitted with a saline lock was used to sample blood before, immediately after, and 15 minutes after intervention. Plasma NE and E concentrations were determined using an enzyme-linked immunosorbent assay. Changes in plasma catecholamine concentrations were analyzed within and between groups using 1- and 2-sample t tests, respectively. ResultsThe plasma samples of 36 subjects (18 treatment, 18 control) were used in the analysis. Mean plasma concentrations of NE and E did not significantly differ between the 2 groups at any time point and did not change significantly after either the manipulative or sham intervention. ConclusionsThe results of this study indicate that a manipulative thrust directed to a hypomobile segment in the upper thoracic spine of asymptomatic subjects does not have a measurable effect on the plasma concentrations of NE or E. These results provide a baseline measure of the sympathetic response to spinal manipulation.

Low social status impairs hypoxia tolerance in rainbow trout (Oncorhynchus mykiss)

In the present study, chronic behavioural stress resulting from low social status affected the physiological responses of rainbow trout (Oncorhynchus mykiss) to a subsequent acute stressor, exposure to hypoxia. Rainbow trout were confined in fork-length matched pairs for 48-72h, and social rank was assigned based on behaviour. Dominant and subordinate fish were then exposed individually to graded hypoxia (final water PO(2), PwO(2)=40Torr). Catecholamine mobilization profiles differed between dominant and subordinate fish. Whereas dominant fish exhibited generally low circulating catecholamine levels until a distinct threshold for release was reached (PwO(2)=51.5Torr corresponding to arterial PO(2), PaO(2)=24.1Torr), plasma catecholamine concentrations in subordinate fish were more variable and identification of a distinct threshold for release was problematic. Among fish that mobilized catecholamines (i.e. circulating catecholamines rose above the 95% confidence interval around the baseline value), however, the circulating levels achieved in subordinate fish were significantly higher (459.9±142.2nmolL(-1), mean±SEM, N=12) than those in dominant fish (130.9±37.9nmolL(-1), N=12). The differences in catecholamine mobilization occurred despite similar P(50) values in dominant (22.0±1.5Torr, N=6) and subordinate (22.1±2.2Torr, N=8) fish, and higher PaO(2) values in subordinate fish under severely hypoxic conditions (i.e. PwO(2)<60Torr). The higher PaO(2) values of subordinate fish likely reflected the greater ventilatory rates and amplitudes exhibited by these fish during severe hypoxia. At the most severe level of hypoxia, subordinate fish were unable to defend arterial blood O(2) content, which fell to approximately half (0.60±0.13mLO(2)g(-1) haemoglobin, N=9) that of dominant fish (1.08±0.09mLO(2)g(-1) haemoglobin, N=9). Collectively, these data indicate that chronic social stress impacts the ability of trout to respond to the additional, acute stress of hypoxia.

Thiopental dose requirements for induction of anaesthesia and subsequent endotracheal intubation in patients with complete spinal cord injuries

Dose requirements of thiopental depend on patient characteristics and infusion rate. We determined thiopental dose requirements for induction of anaesthesia, and the effects of remifentanil on cardiovascular and bispectral index (BIS) responses to tracheal intubation in spinal cord-injured (SCI) patients undergoing general anaesthesia. Twenty patients with traumatic complete SCI undergoing elective surgery were enrolled. Twenty patients without SCI served as control. Anaesthesia was induced with thiopental, followed by remifentanil 1 μg/kg and rocuronium 0.8 mg/kg, and maintained with 2% sevoflurane and 50% nitrous oxide in oxygen after tracheal intubation. Thiopental was administered at a rate of 50 mg/15 s until abolition of the eyelash reflex. Thiopental doses, BIS values, systolic arterial blood pressure (SAP), heart rate (HR) and plasma catecholamine concentrations were measured. Total thiopental dose required to abolish the eyelash reflex based on total body weight (BW) (5.26 ± 0.87 vs. 3.91 ± 1.07 mg/kg, P < 0.001) or lean BW (6.56 ± 1.37 vs. 5.24 ± 1.36 mg/kg, P < 0.01) were significantly smaller in the SCI group than in the control. SAP was decreased by induction of anaesthesia with thiopental and remifentanil, and increased by tracheal intubation in both groups. However, the peak SAP after intubation was smaller in the SCI patients. HR increased significantly above baseline values following intubation in both groups with no significant intergroup differences. Hypertension was more frequent in the control group. Norepinephrine concentrations remained unaltered following intubation in both groups. These results suggest that the dose requirements of thiopental for induction of general anaesthesia and subsequent tracheal intubation are reduced in the SCI patients.

Influence of gender and estrous cycle on plasma and renal catecholamine levels in rats

Several studies have demonstrated that gonadal hormones show significant effects on the brain and signaling pathways of effector organs/cells that respond to neurotransmitters. Since little information is available concerning the impact of male and female gonadal hormones on the renal and peripheral sympathetic system, the objective of this study was to further assess whether and how the renal content and plasma concentration of catecholamines are influenced by gender and the estrous cycle in rats. To achieve this, males Wistar rats were divided into 4 groups: (i) sham (i.e., control), (ii) gonadectomized, (iii) gonadectomized and nandrolone decanoate replacement at physiological levels or (iv) gonadectomized and nandrolone decanoate replacement at high levels. Female Wistar rats were divided into 6 groups: (i) ovariectomized (OVX), (ii) estrogen replacement at physiological levels and (iii) estrogen replacement at at high levels, (iv) progesterone replacement at physiological levels and (v) progesterone replacement at at high levels, and (vi) sham. The sham group was subdivided into four subgroups: (i) proestrus, (ii) estrus, (iii) metaestrus, and (iv) diestrus. Ten days after surgery, the animals were sacrificed and their plasma and renal catecholamine levels measured for intergroup comparisons. Gonadectomy led to an increase in the plasma catecholamine concentration in females, as well as in the renal catecholamine content of both male and female rats. Gonadectomized males also showed a lower level of plasma catecholamine than the controls. The urinary flow, and the fractional excretion of sodium and chloride were significantly increased in gonadectomized males and in the OVX group when compared with their respective sham groups.