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We studied the effect and safety of ephedrine as add-on treatment for patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG), who do not sufficiently respond to standard treatment. Four patients with AChR MG were included in a placebo-controlled, double-blind, and randomised, multiple crossover series of n-of-1 trials. Each n-of-1 trial consisted of 3 cycles, in which two 5-day intervention periods were followed by 2 days washout. In each cycle, ephedrine 50 mg daily in 2 doses was compared with placebo in the alternate treatment period. Primary outcome was a change in QMG score. Add-on treatment with ephedrine compared with placebo improved QMG score by 1.0 point (95% confidence interval 0.21-1.79), which was significant for the group of trial patients as well as for the population treatment effect. Ephedrine also showed a significant trial average treatment effect for all secondary outcomes, improving MG Composite by 2.7, MG-ADL by 1.0 and VAS score for muscle strength by 1.1. Adverse events were mild and included palpitations, tremor and restlessness. Although all ECGs were normal, ephedrine prolonged the corrected QT interval. Ephedrine as add-on treatment for myasthenia gravis resulted in a small but consistent reduction of symptoms and weakness in patients with moderate disease severity., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Drug addiction is classified as a chronic relapse nature brain disease with complicated neurobiology mechanisms. There are an increasing number of researchers that are investigating the possible mechanisms for solving the thorny problem., Methods: The model of chronic addiction of rhesus monkey ephedrine was established, where changes in body weight and behavior were monitored. The expression of cAMP response element binding protein (CREB) in the hippocampus of rhesus monkeys was identified by real-time PCR and Western blot., Results: We were successful in establishing the chronic ephedrine addiction model in the rhesus macaques. They exhibited changes in body weight and behavior. Immunofluorescence showed that CREB was expressed in the nucleus of the hippocampus, and the expression of CREB mRNA and protein in the hippocampus were increased by real-time PCR and Western blot. The CREB positive expression in the hippocampus of the modeling group was significantly higher than in the control group., Conclusions: The changes of body weight and behavior of the rhesus monkeys after ephedrine chronic addiction were significant. The changes of CREB in the hippocampus of rhesus macaques with ephedrine chronic addiction are important molecular mechanisms, and the upregulation of CREB may be involved in the physiological pathology and behavior process in individuals with chronic ephedrine addiction.

Background: It is known that serious refractory hypotension during anesthesia may develop in some patients treated with antidepressants. However the detail of this phenomenon remains unclear., Methods: We performed a retrospective study based on written anesthesia records from April 2011 through September 2012 (n=5,578). We picked up patients who had received various types of antidepressants. We excluded cases in which neuraxial anesthesia had been performed, and preoperative general condi- tion or performed operation had affected hemodynam- ics greatly. 91 of 5,578 patients were included. All 91 patients received general anesthesia using propofol. We checked type of antidepressants taken and use of vasopressors during anesthesia., Results: Type of antidepressants taken by 91 patients had no effect on the frequency of vasopressor administration. However, 7 of 91 patients showed treatment-resistant refractory hypotension by ephed- rine and phenylephrine. Catecholamines (noradrenaline, dobutamine) were effective. Frequency of refractory hypotension was significantly higher with serotonin and noradrenaline reuptake inhibitors (SNRI) or with two combined antidepressants., Conclusions: Type of antidepressants had no effect on frequency of vasopressor administration. Treat- ment-resistant refractory hypotension by ephedrine and phenylephrine was significantly higher with SNRI or two combined antidepressants. Sympathetic nerve activity may be influenced by interaction of anesthetics and antidepressants in some patients.

Likely, maintained organ and notably cerebral perfusion, secures rapid recovery following anesthesia. To secure cerebral blood flow (CBF) at least mean arterial pressure (MAP) and the arterial carbon dioxide tension (PaCO 2 ) need to be considered. CBF is "autoregulated", i.e. stays more or less stable within a MAP of 50-150 mmHg, but the lower limit appears to depend on the central blood volume and/or cardiac output, illustrated by a decrease in CBF at a MAP of 80 mmHg with a compromised central blood volume, while CBF remains constant with a MAP < 40 mmHg, if the central blood volume is maintained. During anesthesia, MAP is often around 50 mmHg meaning that it remains unknown whether CBF is maintained, why an evaluation of CBF, e.g. by near-infrared spectroscopy (NIRS) seems desirable. NIRS is sensitive to changes in PaCOa 2 , detects hypoxemia, identifies cerebral autoregulation as well as regional distribution of CBF. As summarized, especially elderly patients and patients undergoing complex surgery and notably heart and liver surgery, seem to benefit from a strategy focusing on maintaining NIRS-determined cerebral oxygenation during anesthesia. Similarly, NIRS may be applied to guide the ventilatory strategy during anesthesia when there are large deviations in metabolism, seen when clamping of the aorta and with reperfusion of the lower body during open aortic surgery, as with hepatectomy and following reperfusion of the donated liver during liver transplantation surgery. Finally, it is illustrated how NIRS can be applied to select sympathomimetic agents, used to correct anesthesia-induced hypotension in order to preserve CBF and skin oxygenation.

Background: Previous evidence showed that use of phenylephrine was associated with higher umbilical artery pH (UA pH) than ephedrine after elective cesarean delivery (CD). However, the best choice of vasopressor and its effect on funic gases in cases of acute fetal compromise require additional studies., Methods: Ninety parturients showing acute fetal compromise during intrapartum period and taken up for CD (category II) under spinal anesthesia were randomized to receive prophylactic infusion of ephedrine 2.5mg/min or phenylephrine 30μg/min. Systolic blood pressure was targeted between 90% and 110% of baseline. Incidence of fetal acidosis (UA pH <7.2 and/or base deficit >12mmol/L) was recorded. Other parameters of cord gases, Apgar score, need for immediate resuscitation, maternal hemodynamics, and adverse events were also compared., Results: Number of neonates showing acidosis with ephedrine or phenylephrine was comparable (P=.22). Of these, newborns with base deficit >12mmol had low 1-minute Apgar scores (n=15/23). The ephedrine group had higher oxygen content in UA (P=.03). There was no adverse neonatal outcome during the period of observation. Incidence of maternal nausea and vomiting was higher with ephedrine than with phenylephrine (22.2% vs 4.4%; P=.02). Maternal bradycardia was observed with phenylephrine (P=.02)., Conclusion: Our data report similar fetal acidosis with either phenylephrine or ephedrine administered during spinal anesthesia for treating maternal hypotension in cases of emergency CD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Study Objective: To elucidate and compare the pressor response to ephedrine in the prone or supine position during general anesthesia (GA)., Design: Prospective cohort study., Setting: Department of General Surgery or Spine Surgery, Zhongda Hospital, Southeast University, Nanjing, China., Patients: Fifty-six patients who were scheduled to undergo elective surgery in the supine or prone position (n = 28 each) and using a generic GA protocol., Interventions: During surgery, the patients received intravenous (IV) ephedrine when their systolic blood pressure (SBP) decreased to 90 to 110 mm Hg., Measurements: Hemodynamic changes were measured at 1-minute intervals for 10 minutes and were compared with baseline., Main Results: Forty-nine patients (23 in the prone position and 26 in the supine position) completed the study. There were no significant differences between the groups with regard to demographic characteristics, hemodynamic parameters, end-tidal concentration of sevoflurane, and dose of propofol and remifentanil (all P> .05). After the bolus injection of ephedrine, a significant increase in SBP was observed in both groups compared to baseline, but the duration and magnitude of the increase in SBP were longer and greater in the prone position than in the supine position. The magnitude of increase of the mean blood pressure was significantly greater in the prone position compared to the supine position at 2 to 7 minutes after ephedrine injection. Ephedrine could cause significant increase in diastolic blood pressure 2 minutes after IV injection, which could last until at least 9 minutes in the prone position group compared to only for 5 minutes in the supine position group (all P< .05)., Conclusion: Compared to the supine position, the prone position could augment the pressor response to IV ephedrine during GA. Further studies are recommended to identify its association with other confounding factors such as surgery type or duration, patient history of cardiovascular disease, or patient hydration status., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non-stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non-stimulatory thermogenic agents include p-synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. © 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd., (© 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd.)

Introduction: The anesthetized guinea pig (ANES GP) has proven to be an effective small animal model to evaluate cardiac electrophysiologic effects of drug-candidate molecules during lead optimization. While heart rate (HR) corrected QT interval (QTc) is a key variable to determine test article-dependent repolarization effects, ideal correction methods are an area of constant debate given the potential influence of anesthesia, autonomic tone, species, strain and gender on the QT/HR relationship. The aim of this study was to characterize the ability of common correction formulas to normalize rate-dependent effects on the QT interval in the ketamine/xylazine ANES GP., Methods: Atrial pacing (n=10), ivabradine or ephedrine (n=6/group) infusions were used, respectively to evaluate the effects of a wide range of HRs on the QT/HR relationship. Correction formulas (Bazett [QTcb], Fridericia [QTcf] and Van de Water [QTcVdW]) were applied and the best fit formula was determined with the aid of the slope of their QT-HR linear relationship., Results: From 100 to 220bpm, QTcb underestimated the change in QT interval duration (QT/HR slope=0.35 to 0.67). However, QTcVdW was more appropriate in this HR range (QT/HR slope=-0.07 and 0.09). At higher HRs (>220bpm), QTcb performed better (QT/HR slope=-0.02 and 0.07) as compared to QTcf (QT/HR slope=-0.18 to -0.1) and QTcVdW (QT/HR slope=-0.2 to -0.17) (p<0.01). All the correction formulas identified dofetilide- and sotalol-dependent repolarization delay (n=6/group) but QTcb and QTcf demonstrated reduced sensitivity as compared to fixed cardiac pacing (p<0.01). In contrast, QTcVdW resulted in an apparent underestimation of the QT interval duration at HR levels above the basal ketamine/xylazine ANES GP HRs (>220bpm) with ephedrine (n=6)., Discussion: The best fit correction formula in the ANES GP was highly dependent on the HR range. In the ketamine/xylazine model, QTcVdW performed best with HR <220bpm and QTcb performed best with HR >220bpm. The QTcVdW correction formula was thus selected in the ketamine/xylazine ANES GP since HRs in this model are generally within the optimal range for this correction formula., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Study Objectives: To evaluate changes in cerebral tissue oxygen index (TOI) values under the beach chair position before and during general anesthesia in surgical patients with or without cardiovascular risk factors., Design: Prospective study., Setting: Operating room in the university hospital., Patients: Ninety-one patients undergoing surgery, including healthy patients (n = 28), patients with 1 cardiovascular risk factor (n = 33), and those with more than 1 risk factor (n = 30)., Interventions and Measurements: Cerebral TOI the day before and during general anesthesia was evaluated using a near-infrared spectroscopy NIRO-200 (Hamamatsu Photonics, Hamamatsu, Japan) for each patient. The initial TOI measurement in the supine position after a 10-minute rest or 10 minute after the endotracheal intubation was followed by measurements in 30° and subsequent 60° upright position for 5 minutes. Phenylephrine 0.1 mg and/or ephedrine 4 mg was administered intravenously to maintain mean blood pressure above 60 mm Hg accordingly., Main Results: The beach chair position decreased mean arterial blood pressure and heart rate under general anesthesia, although patients with more than 1 cardiovascular risk factor needed significantly more phenylephrine doses to maintain mean blood pressure above 60 mm Hg. Values of TOI were within the normal range of about 70% before and during anesthesia in all groups., Conclusions: The beach chair position under general anesthesia did not alter cerebral oxygenation in patients with or without cardiovascular risk factors showing normal preoperative cerebral TOI values when the mean blood pressure was maintained above 60 mm Hg. The careful management using the cerebral oxygenation monitoring appears to maintain cerebral perfusion in the beach chair position during general anesthesia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims/hypothesis: Brown adipose tissue (BAT) activation increases energy expenditure and may have therapeutic potential to combat obesity. The primary activating and adaptive signal for BAT is via β-adrenergic signalling. We previously demonstrated that human BAT is acutely responsive to oral administration of the sympathomimetic, ephedrine. Here we aimed to determine whether adaptive thermogenesis can be induced via chronic treatment with ephedrine., Methods: Twenty-three healthy young men, recruited from the general public in Melbourne, Australia, who were non-smokers, physically inactive and non-medicated with no prior history of cardiovascular disease or diabetes were recruited for this study. They were assigned to receive either 1.5 mg kg(-1) day(-1) ephedrine ('active' group; n = 12, age 23 ± 1 years, BMI 24 ± 1 kg/m(2)) or placebo (n = 11; 22 ± 2 years, 23 ± 2 kg/m(2)) for 28 days in a randomised (computer-generated random order sequence), placebo-controlled, parallel-group trial. Participants and all investigators were blinded to treatments. Body composition was measured before and after the intervention by dual energy X-ray absorptiometry. BAT activity, measured via (18)F-fluorodeoxyglucose positron emission tomography-computed tomography, in response to a single dose of 2.5 mg/kg ephedrine, was the primary outcome measure to be determined before and after the 28 day treatment period., Results: Twenty-eight individuals were randomised and consented to the study. Twenty-three completed the trial and only these participants were included in the final analyses. After 28 days of treatment, the active group lost a significant amount of total body fat (placebo 1.1 ± 0.3 kg, ephedrine -0.9 ± 0.5 kg; p < 0.01) and visceral fat (placebo 6.4 ± 19.1 g, ephedrine -134 ± 43 g; p < 0.01), with no change in lean mass or bone mineral content compared with the placebo group. In response to acute ephedrine, BAT activity (change in mean standardised uptake value: placebo -3 ± 7%, ephedrine -22 ± 6%) and the increase in systolic blood pressure were significantly reduced (p < 0.05) in the active group compared with placebo., Conclusions/interpretation: Chronic ephedrine treatment reduced body fat content, but this was not associated with an increase in BAT activity. Rather, chronic ephedrine suppressed BAT glucose disposal, suggesting that chronic ephedrine treatment decreased, rather than increased, BAT activity., Trial Registration: ClinicalTrials.gov NCT02236962 FUNDING: This study was funded by the National Health and Medical Research Council of Australia Program Grant (1036352) and the OIS scheme from the Victorian State Government.

Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery. Clarifying the bioactivity of the combined mechanisms of the ingredients in complex traditional Chinese medicine formulas is challenging. A classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment for prevalent chronic lung disease, was investigated in this work. A mutually enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) characterization system was proposed, coupled with a dual-luciferase reporter assay for β2AR-agonist cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed. The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence. The relaxant and contractile responses of airway smooth muscle are regulated by crosstalk between the intracellular cAMP and calcium signaling pathways. Our data indicated the non-selective βAR agonist ephedrine as the principal bronchodilator of the formula, whereas the lignin ingredients served as adjuvant ingredients. A greater understanding of the mechanisms governing the control of these pathways, based on conventional wisdom, could lead to the identification of novel therapeutic targets or new agents for the treatment of asthma and COPD.

Cardiolipin (CL) is crucial for mitochondrial energy metabolism and structural integrity. Alterations in CL quantity or CL species have been associated with mitochondrial dysfunction in several pathological conditions and diseases, including mitochondrial dysfunction-related compound attrition and post-market withdrawal of promising drugs. Here we report alterations in the CL profiles in conjunction with morphology of soleus muscle (SM) and brown adipose tissue (BAT) in diet-induced obese (DIO) mice, subjected to ephedrine treatment (EPH: 200 mg kg(-1)  day(-1) orally), treadmill exercise (EX: 10 meters per min, 1 h per day), or dietary restriction (DR: 25% less of mean food consumed by the EX group) for 7 days. Mice from the DR and EPH groups had a significant decrease in percent body weight and reduced fat mass compared with DIO controls. Morphologic alterations in the BAT included brown adipocytes with reduced cytoplasmic lipid droplets and increased cytoplasmic eosinophilia in the EX, DR and EPH groups. Increased cytoplasmic eosinophilia in the BAT was ultrastructurally manifested by increased mitochondrial cristae, fenestration of mitochondrial cristae, increased electron density of mitochondrial matrix, and increased complexity of shape and elongation of mitochondria. Mitochondrial ultrastructural alterations in the SM of the EX and DR groups included increased mitochondrial cristae, cup-shaped mitochondria and mitochondrial degeneration. All four CL species (tri-linoleoyl-mono-docosahexaenoyl, tetralinoleoyl, tri-linoleoyl-mono-oleoyl, and di-linoleoyl-di-oleoyl) were increased in the BAT of the DR and EPH groups and in the SM of the EPH and EX groups. In conclusion, cardiolipin profiling supported standard methods for assessing mitochondrial biogenesis and health, and may serve as a potential marker of mitochondrial dysfunction in preclinical toxicity studies., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: Phenylephrine and ephedrine affect frontal lobe oxygenation ([Formula: see text]) differently when assessed by spatially resolved near infrared spectroscopy. We evaluated the effect of phenylephrine and ephedrine on extra- vs intra-cerebral blood flow and on [Formula: see text]., Methods: In 10 healthy males (age 20-54 yr), phenylephrine or ephedrine was infused for an ∼20 mm Hg increase in mean arterial pressure. Cerebral oxygenation (SavO₂) was calculated from the arterial and jugular bulb oxygen saturations. Blood flow in the internal carotid artery (ICAf) and blood flow in the external carotid artery (ECAf) were assessed by duplex ultrasonography. Invos-5100c (SinvosO₂) and Foresight (SforeO₂) determined [Formula: see text] while forehead skin oxygenation (SskinO₂) was assessed., Results: Phenylephrine reduced SforeO₂ by 6.9% (95% confidence interval: 4.8-9.0%; P<0.0001), SinvosO₂ by 10.5 (8.2-12.9%; P<0.0001), and ECAf (6-28%; P=0.0001), but increased ICAf (5-21%; P=0.003) albeit with no consequence for SskinO₂ or SavO₂. In contrast, SforeO₂ was maintained with administration of ephedrine while SinvosO₂ and SavO₂ decreased [by 3.1 (0.7-4.5%; P=0.017) and 2.1 (0.5-3.3%; P=0.012)] as arterial carbon dioxide pressure decreased (P=0.003). ICAf was stable and ECAf increased by 11 (4-18%; P=0.005) with administration of ephedrine while SskinO₂ did not change., Conclusions: The effect of phenylephrine on ScO₂ is governed by a decrease in external carotid blood flow since it increases cerebral blood flow as determined by flow in the internal carotid artery. In contrast, ScO₂ is largely maintained with administration of ephedrine because blood flow to extracerebral tissue increases., (© The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Unlabelled: Ephedrine/caffeine combination (EC) has been shown to induce a small-to-moderate weight loss in obese patients. Several mechanisms have been proposed, among which an increased thermogenic capacity of skeletal muscle consequent to the EC-induced up-regulation of uncoupling protein 3 (UCP3) gene expression. We did a parallel group double-blind, placebo-controlled, 4-week trial to investigate this hypothesis. Thirteen morbidly obese women (25-52 years of age, body-mass index 48.0±4.0 kg/m2, range 41.1-57.6) were randomly assigned to EC (200/20 mg, n = 6) or to placebo (n = 7) administered three times a day orally, before undergoing bariatric surgery. All individuals had an energy-deficit diet equal to about 70% of resting metabolic rate (RMR) diet (mean 5769±1105 kJ/day). The RMR analysed by intention to treat and the UCP3 (long and short isoform) mRNA levels in rectus abdominis were the primary outcomes. Body weight, plasma levels of adrenaline, noradrenaline, triglycerides, free fatty acids, glycerol, TSH, fT4, and fT3 were assessed, as well as fasting glucose, insulin and HOMA index, at baseline and at the end of treatments. Body weight loss was evident in both groups when compared to baseline values (overall -5.2±3.2%, p<0.0001) without significant differences between the treated groups. EC treatment increased the RMR (+9.2±6.8%, p = 0.020), differently from placebo which was linked to a reduction of RMR (-7.6±6.5%, p = 0.029). No significant differences were seen in other metabolic parameters. Notably, no changes of either UCP3 short or UCP3 long isoform mRNA levels were evident between EC and placebo group. Our study provides evidence that 4-week EC administration resulted in a pronounced thermogenic effect not related to muscle UCP3 gene expression and weight loss in morbidly obese females under controlled conditions., Trial Registration: ClinicalTrials.gov NCT02048215.

Ethnopharmacological Relevance: The herbal decoction is a complex dispersion system containing solutes, colloid, aggregates, emulsions and precipitates. In which phase bioactive phytochemicals are dispersed determines their delivery, action and metabolism. This study took ephedrine, a well-studied and widely used phytochemical, as an example to elucidate its exact distribution in the phases of Ma-Xing-Shi-Gan-Tang decoction (MXSGT), which is an Ephedra sinica Stapf. containing traditional Chinese medicinal formula, and the biological meaning of this distribution correspondingly. It may provide an important update to the safety and efficacy assessment of the herbal decoction and its active phytochemicals., Materials and Methods: In this study, the decoction was fractionated with size-exclusion chromatography coupled with multi-angle laser light scattering detector. The morphology of fractionated nanoparticles was observed with AFM and SEM. The bioactivities of the decoction, the ephedrine alkaloids loaded NPs (prepared by chromatography isolation) and the synthetic ephedrine were assessed by cell proliferation tests using five cell lines, namely Caco-2, L-02, Hep-G2, NR-8383, and Hela-229., Results: Nanoparticles with radii of gyration ranged from 50 to 150 nm were isolated, in spherical shape. Further analysis of nanoparticles on the subsequent reversed phase chromatography revealed that the majority of ephedrine (99.7%) and pseudoephedrine (95.5%) were associated with these nanoparticles, rather than dispersed freely in the real solution. The addition of both the herbal decoction and the separated ephedrine-loaded nanoparticles reserved higher cell viability/proliferation than that of the sole synthetic ephedrine among the Caco-2, L-02, Hep-G2, and NR-8383 cells. In contrast, the nanoparticles reduced the proliferating power of ephedrine on Hela-229 cells. In general, the ephedrine-loaded NPs conducted the intermediate influences on the cell viability, in either way., Conclusions: The colloidal nanoparticles were separated from the decoction. The association of ephedrine alkaloids with nanoparticles was demonstrated and may have changed the bioactivity of the alkaloids. The naturally occurred colloidal nanoparticles may play an important role in the pharmacological properties of both the decoction and its active phytochemicals, therefore warrant further studies., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Plant alkaloids are found in foods, beverages, and supplements consumed by athletes for daily nutrition, performance enhancement, and immune function improvement. This paper examined possible immunomodulatory roles of alkaloids in exercise contexts, with a focus on human studies. Four representative groups were scrutinized: (a) caffeine (guaranine, mateine); (b) theophylline and its isomers, theobromine and paraxanthine; (c) ginger alkaloids including gingerols and shogaol; and (d) ephedra alkaloids such as ephedrine and pseudoephedrine. Emerging or prospective alkaloid sources (Goji berry, Noni berry, and bloodroot) were also considered. Human in vitro and in vivo studies on alkaloids and immune function were often conflicting. Caffeine may be immunomodulatory in vivo depending on subject characteristics, exercise characteristics, and immune parameters measured. Caffeine may exhibit antioxidant capacities. Ginger may exert in vivo anti-inflammatory effects in certain populations, but it is unclear whether these effects are due to alkaloids or other biochemicals. Evidence for an immunomodulatory role of alkaloids in energy drinks, cocoa, or ephedra products in vivo is weak to nonexistent. For alkaloid sources derived from plants, variability in the reviewed studies may be due to the presence of unrecognized alkaloids or non-alkaloid compounds (which may themselves be immunomodulatory), and pre-experimental factors such as agricultural or manufacturing differences. Athletes should not look to alkaloids or alkaloid-rich sources as a means of improving immune function given their inconsistent activities, safety concerns, and lack of commercial regulation.

Background and Objective: Vasopressors ephedrine and phenylephrine are commonly used with spinal anesthesia during cesarean delivery. Studies on them have focused on the period before the umbilical cord is clamped, although anesthesia is continuously administered throughout and after this event. This study aimed to compare the effects of these drugs on maternal hemodynamics at and after clamping of the umbilical cord., Study Design: Prospective, randomized, double-blind study., Setting: Parturients (n = 60) scheduled for elective cesarean delivery were randomly divided into an ephedrine group and a phenylephrine group. Each woman received an intrathecal injection of bupivacaine (7.5 mg)., Measurements: Patients in the ephedrine and phenylephrine groups were infused continuously with ephedrine (0.02 mg×kg-1×min-1) or phenylephrine (0.25 μg×kg-1×min-1), respectively, from immediately after the injection of bupivacaine until termination 10 minutes after the umbilical cord was clamped (the endpoint). Hemodynamic changes were recorded., Results: After clamping the umbilical cord, the patients who were administered ephedrine experienced significant increases in heart rate (89 ± 11 beats/min to 106 ± 15 beats/min), cardiac output (6.4 ± 0.9 l/min to 7.6 ± 1.2 l/min) and cardiac index (3.5 ± 0.39 l×min-1×m-2 to 4.3 ± 0.48 l×min-1×m-2), while the systemic vascular resistance decreased (908 ± 296 dyne·s/cm5 to 711 ± 285 dyne·s/cm5). Such differences were not observed in the patients who received phenylephrine. Moreover, the heart rate of patients administered ephedrine was higher than that of patients given phenylephrine after clamping the umbilical cord., Conclusion: Continuous infusion of phenylephrine during cesarean delivery maintains a stable maternal hemodynamic status better than ephedrine.

The paper is a review of literature data on interaction of the mammalian erythrocyte acetylcholinesterase and blood serum butyrylcholinesterase with a group of isomer complex ester derivatives (acetates, propionates, butyrates, valerates, and isobutyrates) of bases and iodomethylates of ephedrine and its enantiomer pseudoephedrine. For 20 alkaloid monoesters, parameters of enzymatic hydrolysis are determined and their certain specificity toward acetylcholinesterase is revealed, whereas 5 diesters of iodomethylates of pseudoephedrine were hydrolyzed only by butyrylcholinesterase. The studied 20 aklaloid diesters and 10 trimethylammonium derivatives turned out to be non-competitive reversible inhibitors of acetylcholinesterase and competitive inhibitors of butyrylcholinesterase. The performed for the first time isomer and enantiomer analysis "structure-efficiency" has shown that in most cases it is possible to state the greater comlementarity of the catalytical surface of enzymes for ligands of the pseudoephedrine structure, such differentiation being realized more often at the reversible inhibition of enzymes. pseudoephedrine.

In the slow channel congenital myasthenic syndrome mutations in genes encoding the muscle acetylcholine receptor give rise to prolonged ion channel activations. The resulting cation overload in the postsynaptic region leads to damage of synaptic structures, impaired neuromuscular transmission and fatigable muscle weakness. Previously we identified and characterised in detail the properties of the slow channel syndrome mutation εL221F. Here, using this mutation, we generate a transgenic mouse model for the slow channel syndrome that expresses mutant human ε-subunits harbouring an EGFP tag within the M3-M4 cytoplasmic region, driven by a ~1500 bp region of the CHRNB promoter. Fluorescent mutant acetylcholine receptors are assembled, cluster at the motor endplates and give rise to a disease model that mirrors the human condition. Mice demonstrate mild fatigable muscle weakness, prolonged endplate and miniature endplate potentials, and variable degeneration of the postsynaptic membrane. We use our model to investigate ephedrine as a potential treatment. Mice were assessed before and after six weeks on oral ephedrine (serum ephedrine concentration 89 ± 3 ng/ml) using an inverted screen test and in vivo electromyography. Treated mice demonstrated modest benefit for screen hang time, and in measures of compound muscle action potentials and mean jitter that did not reach statistical significance. Ephedrine and salbutamol show clear benefit when used in the treatment of DOK7 or COLQ congenital myasthenic syndromes. Our results highlight only a modest potential benefit of these β2-adrenergic receptor agonists for the treatment of the slow channel syndrome., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effects of combination caffeine/ephedrine and leptin A-200 on visceral fat mass and weight loss over 24 weeks., Design and Methods: In this randomized, double-blind, parallel-arm trial, 90 obese subjects received one of the three treatments for 24 weeks: 200 mg caffeine/20 mg ephedrine t.i.d. (CE), leptin A-200 (recombinant methionyl human Fc-leptin, 20 mg q.d.) (L), or combination leptin A-200 and caffeine/ephedrine (LCE). Outcomes included change in weight, visceral fat mass by computed tomography, lean mass and fat mass by dual energy X-ray absorptiometry., Results: Groups treated with CE and LCE lost significant amounts of weight (-5.9 ± 1.2% and -6.5 ± 1.1%, P < 0.05) and whole body fat mass (-9.6 ± 2.4% and -12.4 ± 2.3%, P < 0.05) compared to leptin only group. Only treatment with LCE significantly reduced visceral fat mass (-11.0 ± 3.3%, P < 0.05). There were no differences in lean mass between treatment groups., Conclusions: Our study provides evidence that CE is a modestly effective weight loss agent and produces significant reductions in fat mass. Leptin A-200 was not effective in producing weight loss and did not have any significant additive or synergistic actions when combined with CE., (Copyright © 2013 The Obesity Society.)

Given the underlying assumption that reasonable maternal hemodynamics can be achieved with either ephedrine or phenylephrine, this focused meta-analysis addresses the impact of vasopressor choice on resultant neonatal Apgar scores during regional anesthesia. The literature was systematically searched for randomized trials of obstetric vasopressor use employing standard search tools. Only the highest quality trials were included. Of 142 studies retrieved, 9 met the defined inclusion criteria. Apgar scores at 1 and 5 minutes in the ephedrine group (served as control) vs the phenylephrine group did not differ at either time epoch; no abnormal values prevailed in either group (relative risk, 0.88; CI, 0.79-1.16). This meta-analysis focused on the most clinically relevant, immediately available information pertinent in the obstetric suite, the Apgar score, and found that ephedrine and phenylephrine did not differ in their effect on this metric. The current meta-analysis provides an updated, evidence-based validation of vasopressor use from the American Society of Anesthesiologists' 2007 "Practice Guidelines for Obstetric Anesthesia".

Approaches for controlling inflammatory responses and reducing the mortality rate of septic patients remain clinically ineffective; new drugs need to be identified that can induce anti-inflammatory responses. Ephedrine hydrochloride (EH) is a compound that is widely used in cardiovascular diseases, especially to treat hypotension caused by either anesthesia or overdose of antihypertensive drugs. In this study, we reported that EH also plays an important role in the control of the inflammatory response. EH increased IL-10 and decreased proinflammatory cytokine (IL-6, tumor-necrosis factor (TNF)-α, IL-12 and IL-1β) expression in primary peritoneal macrophages and Raw264.7 cells treated with peptidoglycan (PGN), a Gram-positive cell wall component. The anti-inflammatory role of EH was also demonstrated in an experimental mouse model of peritonitis induced by intraperitoneal PGN injection. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway was found to be responsible for the EH-mediated increase in IL-10 production and decrease in IL-6 expression. Therefore, our results illustrated that EH can help maintain immune equilibrium and diminish host damage by balancing the production of pro- and anti-inflammatory cytokines after PGN challenge. EH may be a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection.

Objective: To assess the cardiopulmonary effects of ephedrine and phenylephrine for management of isoflurane-induced hypotension in horses., Study Design: Prospective randomized clinical study., Animals: Fourteen isoflurane-anesthetized horses undergoing digital palmar neurectomy., Methods: Ephedrine (EPH group; 0.02 mg kg(-1) minute(-1); n = 7) or phenylephrine (PHE group; 0.002 mg kg(-1) minute(-1); n = 7) was administered to all horses when mean arterial pressure (MAP) was <60 mmHg. The infusions were ended when the target MAP was achieved, corresponding to a 50% increase over the pre-infusion MAP (baseline). The horses were instrumented with an arterial catheter to measure blood pressure and allow the collection of blood for pH and blood-gas analysis and a Swan-Ganz catheter for measurement of cardiac output using thermodilution. Cardiopulmonary parameters were recorded at baseline and at 5, 30, 60 and 90 minutes after achieving the target MAP., Results: In both groups, the MAP and systemic vascular resistance (SVR) increased significantly at 5, 30, 60 and 90 minutes post infusion compared to baseline (p < 0.05). The EPH group had a significant increase in cardiac index (CI) and systemic oxygen delivery index at 5, 30, 60 and 90 minutes post infusion compared to baseline (p < 0.05) and compared to the PHE group (p < 0.05). The PHE group had significantly higher SVR and no decrease in oxygen extraction compared with the EPH group at 30, 60 and 90 minutes post infusion (p < 0.05). No significant differences in ventilatory parameters were observed between groups after the infusion., Conclusions: Ephedrine increased the MAP by increasing CI and SVR. Phenylephrine increased MAP by increasing SVR but cardiac index decreased. Ephedrine resulted in better tissue oxygenation than phenylephrine., Clinical Relevance: Ephedrine would be preferable to phenylephrine to treat isoflurane-induced hypotension in horses since it increases blood flow and pressure.

In neutrophils, activation of the β2-adrenergic receptor (β2AR), a Gs-coupled receptor, inhibits inflammatory responses, which could be therapeutically exploited. The aim of this study was to evaluate the effects of various β2AR ligands on adenosine-3',5'-cyclic monophosphate (cAMP) accumulation and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced superoxide anion (O2(•-)) production in human neutrophils and to probe the concept of ligand-specific receptor conformations (also referred to as functional selectivity or biased signaling) in a native cell system. This is an important question because so far, evidence for functional selectivity has been predominantly obtained with recombinant systems, due to the inherent difficulties to genetically manipulate human native cells. cAMP concentration was determined by HPLC/tandem mass spectrometry, and O2(•-) formation was assessed by superoxide dismutase-inhibitable reduction of ferricytochrome c. β2AR agonists were generally more potent in inhibiting fMLP-induced O2(•-) production than in stimulating cAMP accumulation. (-)-Ephedrine and dichloroisoproterenol were devoid of any agonistic activity in the cAMP assay, but partially inhibited fMLP-induced O2(•-) production. Moreover, (-)-adrenaline was equi-efficacious in both assays whereas the efficacy of salbutamol was more than two-fold higher in the O2(•-) assay. Functional selectivity was visualized by deviations of ligand potencies and efficacies from linear correlations for various parameters. We obtained no evidence for involvement of protein kinase A in the inhibition of fMLP-induced O2(•-) production after β2AR-stimulation although cAMP-increasing substances inhibited O2(•-) production. Taken together, our data corroborate the concept of ligand-specific receptor conformations with unique signaling capabilities in native human cells and suggest that the β2AR inhibits O2(•-) production in a cAMP-independent manner.

Ephedrine (Eph) is one of alkaloids that has been isolated from the ancient herb ephedra (ma huang) and is used as the treatment of asthma, hypotension and fatigue. However, its molecular mechanism remains unknown. Thioredoxin-1 (Trx-1) is a redox regulating protein, which has various biological activities, including regulating transcription factor DNA binding activity and neuroprotection. In this study, we found that Eph induced Trx-1 expression, which was inhibited by propranolol (β-adrenergic receptor inhibitor), but not by phenoxybenzamine (α-adrenergic receptor inhibitor) in rat pheochromocytoma PC12 cells. Moreover, the increase of Trx-1 expression was inhibited by SQ22536 (adenylyl cyclase inhibitor) and H-89 (protein kinase A inhibitor). Interestingly, the effect of Eph on dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32) was similar to Trx-1. Thus, the relationship between Trx-1 and DARPP-32 was further studied. The DARPP-32 siRNA significantly reduced Trx-1 expression, but Trx-1 siRNA did not exchange DARPP-32. These results suggested that Eph induced the Trx-1 expression through β-adrenergic receptor/cyclic AMP/PKA/DARPP-32 signaling pathway. Furthermore, Eph induced PKA-mediated cyclic AMP response element-binding protein (CREB) phosphorylation. Down-regulation of DARPP-32 expression decreased phosphorylated CREB. In addition, Eph had a significant effect on the viability of the rat pheochromocytoma PC12 cells through β-adrenergic receptors. Trx-1 may play an important role in the actions of Eph., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Ephedrine is a direct/indirect vasoactive drug. In addition, it also possesses intrinsic local anesthetic properties, mainly due to its sodium-channel blockage. We investigated whether ephedrine demonstrates a synergistic effect with bupivacaine and lidocaine when injected via a spinal catheter into the spinal space of rats., Methods: Spinal catheters were surgically placed in 47 rats (n = 8 per group; 7 rats were excluded.) Bupivacaine, lidocaine, and ephedrine in various concentrations and constant volumes (60 μL) were injected into the spinal catheters to determine the equipotency of each drug. Ephedrine in combination with either bupivacaine or lidocaine was then injected into the spinal catheters., Results: Ephedrine demonstrated statistically significant synergistic effects with bupivacaine as well as with lidocaine in fixed combinations. The combination index reflecting a synergistic effect was 0.792 (95% confidence interval: 0.665-0.919) for ephedrine + bupivacaine and 0.663 (95% confidence interval: 0.532-0.794) for ephedrine + lidocaine., Conclusion: Ephedrine combined with either bupivacaine or lidocaine acted synergistically to block motor function and has the potential to reduce the amount of local anesthetic needed for spinal block. The synergistic effect of ephedrine in combination with local anesthetics is an interesting pharmacological phenomenon that warrants further clinical evaluation.

Aims/hypothesis: Brown adipose tissue (BAT) activation increases energy consumption and may help in the treatment of obesity. Cold exposure is the main physiological stimulus for BAT thermogenesis and the sympathetic nervous system, which innervates BAT, is essential in this process. However, cold-induced BAT activation is impaired in obese humans. To explore the therapeutic potential of BAT, it is essential to determine whether pharmacological agents can activate BAT., Methods: We aimed to determine whether BAT can be activated in lean and obese humans after acute administration of an orally bioavailable sympathomimetic. In a randomised, double-blinded, crossover trial, we administered 2.5 mg/kg of oral ephedrine to nine lean (BMI 22 ± 1 kg/m²) and nine obese (BMI 36 ± 1 kg/m²) young men. On a separate day, a placebo was administered to the same participants. BAT activity was assessed by measuring glucose uptake with [¹⁸F]fluorodeoxyglucose and positron emission tomography-computed tomography imaging., Results: BAT activity was increased by ephedrine compared with placebo in the lean, but unchanged in the obese, participants. The change in BAT activity after ephedrine compared with placebo was negatively correlated with various indices of body fatness., Conclusions/interpretation: BAT can be activated via acute, oral administration of the sympathomimetic ephedrine in lean, but not in obese humans.

Congenital myasthenic syndrome shows a wide clinical heterogeneity. However, the unusual pattern of muscle weakness and the presence of variable degree of muscle pathology, subtle electrophysiological abnormalities and lack of circadian variability of symptoms may complicate its recognition. We have previously reported a Palestinian family with suspected congenital muscular dystrophy and linkage to chromosome 4p16.3. As the DOK7 gene is located in this genetic interval, we considered it a potential candidate for this condition. Patients showed a homozygous DOK7 pathogenic mutation (c.957delC). We have re-examined six patients and found permanent limb-girdle weakness, but also episodic crises without clear precipitating factors. Following the revised diagnosis, patients were treated with salbutamol for 8 months with significant improvement in their muscle strength and function. This family needs to be reclassified as congenital myasthenic syndrome rather than congenital muscular dystrophy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Autonomic drugs are used clinically to either imitate or inhibit the normal functions of the sympathetic and parasympathetic nervous systems. A large number of additional drug classes also interact with these systems to produce a stunning number of possible side effects. This article reviews the basic function of the autonomic nervous system and the various drug classes that act within these neural synapses.

Background: Application of positive end-expiratory pressure (PEEP) has been used to increase the cross-sectional area (CSA) of the right internal jugular vein (IJV) in order to facilitate catheterisation. We aimed to determine the PEEP level at which the maximum increase of CSA occurred., Methods: We enrolled 60 American Society of Anesthesiologists physical status I and II patients undergoing general endotracheal anaesthesia. The CSA was measured in the supine position with no PEEP (control condition, P0) and after applying five different PEEPs in random order: 3 (P3), 6 (P6), 9 (P9), 12 (P12), and 15 (P15) cm H(2) O. Ultrasound was used to measure and record the CSA of the right IJV at the level of the cricoid cartilage., Results: All PEEP levels increased the CSA of the right IJV relative to the control (all P < 0.05). On average, P3, P6, P9, P12, and P15 increased the CSA by 21.5, 37.4, 51.9, 66.5, and 72.4%, respectively. There was no significant increase in CSA above a PEEP of 12 cm H(2) O., Conclusion: The application of PEEP effectively increases the CSA of the right IJV. The PEEP giving the largest CSA is 12 cm H(2) O., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Background: Ephedrine is used in treatment of hypotension during anesthesia. We investigated its effects on the psychomotor recovery and its potential adverse reactions on cardiorespiratory functions in rhesus monkeys., Methods: The monkeys received 50 μg/kg medetomidine, 2.0 mg/kg S-ketamine with 150 IU hyaluronidase i.m. Pulse rate, blood pressure and saturation of haemoglobin were monitored for 20 minutes. Thereafter, 1 mg/kg of ephedrine or a placebo was administered i.m. and behavioural changes, pulse rate, blood pressure and saturation of haemoglobin were monitored every 5 minutes., Results: Ephedrine shortened recovery from anaesthesia from 80.4 ± 25.8 to 14.83 ± 13.70 minutes. Ephedrine also increased oxygen saturation of haemoglobin and systolic blood pressure and caused significant decrease in pulse rate 5 minutes after its administration., Conclusions: Ephedrine can be successfully used to accelerate psychomotor recovery after the use of common anesthetic protocols combining dissociative anesthetic agent and alpha 2-adrenoceptor agonist in primates., (© 2012 John Wiley & Sons A/S.)

Purpose of Review: This review assesses the maternal and fetal effects of vasopressor administration during spinal anaesthesia for caesarean delivery, with emphasis on recent findings., Recent Findings: Maternal heart rate is a good surrogate for cardiac output. The initial hypotensive effect of spinal anaesthesia is caused by a rapid decrease in systemic vascular resistance, which makes α-agonists the logical first-line therapy. Effective prophylactic phenylephrine administration can be associated with reduced maternal cardiac output, but this has not been associated with adverse maternal or fetal effects. Prophylactic phenylephrine infusion can cause hypertension if increasing arterial pressure does not trigger a timely reduction in the rate of administration. Phenylephrine has been used safely in mothers with cardiac disease and in pregnancies with suspected fetal compromise. Fetal genotype may increase resistance to ephedrine-induced acidosis. The combination of vagolytics and vasopressors has caused maternal hypertensive crises with serious adverse outcome., Summary: Phenylephrine is the current vasopressor of choice for the prevention of maternal hypotension and nausea. Phenylephrine regimens need to be developed that can reliably and safely be used with noninvasive blood pressure cycle times less frequent than every minute. Further vasopressor should be used with caution when vagolytic therapy is, quite rightly, used to treat bradycardia associated with hypotension.

Sepsis and its derivative endotoxic shock are still serious conditions with high mortality in the intensive care unit. The mechanisms that ensure the balance of proinflammatory cytokines and anti-inflammatory cytokine production are of particular importance. As an active α- and β-adrenergic agonist, ephedrine hydrochloride (EH) is a widely used agent for cardiovascular diseases, especially boosting blood pressure. Here we demonstrate that EH increased Toll-like receptor 4 (TLR4)-mediated production of interleukin 10 (IL-10) through p38 MAPK activation. Simultaneously, EH negatively regulated the production of proinflammatory cytokines. Consistently, EH increased lipopolysaccharide (LPS)-induced serum IL-10 and inhibited tumor necrotic factor-α (TNFα) production in vivo. As a result, EH treatment protected mice from endotoxic shock by lethal LPS challenge. In brief, our data demonstrated that EH could contribute to immune homeostasis by balancing the production of proinflammatory cytokines and anti-inflammatory cytokine in TLR4 signaling. This study provides a potential usage of EH in autoimmunologic diseases or other severe inflammations., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This study investigated the effects of a single oral administration of ephedrine (2 mg/kg) or phenylpropanolamine (PPA) (1.5 mg/kg) on the vesico-urethral and cardiovascular functions in continent female dogs. Urethral pressure profilometry (UPP), arterial blood pressures and heart rate were measured in five control dogs and after single-dose treatment with ephedrine or PPA at T(0), T(2h), T(4h), T(6h), T(12h), T(18h) and T(24h). UPPs were performed under propofol anaesthesia and other measurements were performed on awake dogs. A telemetric urodynamic investigation was performed on three additional dogs for 24 h after the administration of each drug. Urethral pressures increased over 4-6 h and urethral functional lengths increased 2-6h after administration of both drugs. During micturition, a decrease in detrusor pressure coupled with an increase in bladder volume was observed after ephedrine administration and there was also an increase in bladder volume after PPA had been given. With both drugs increased arterial blood pressures at 4-6 h were compensated by a decreased heart rate over 12 h. Urethral function was improved after both ephedrine and PPA, and bladder function also improved during micturition following ephedrine., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: This study was designed to show the relationship between tricuspid annular plane systolic excursion (TAPSE) and stroke volume (SV) by thermodilution using three different methods and also to assess whether TAPSE can track hemodynamic changes associated with volume loading and ephedrine administration., Methods: This was an observational study in 61 elective patients with a pulmonary artery catheter who were undergoing coronary artery bypass graft surgery in a cardiac surgical centre. We measured TAPSE by three methods using transesophageal echocardiography: M mode, speckle tracking at the lateral wall, and tissue tracking at the inferior wall. There were two interventions: leg raising (volume recruitment) or administration of ephedrine 5 mg iv. Echo and hemodynamic measurements were performed before and after each intervention., Results: Eleven patients were excluded due to poor imaging. There were 26 patients in the leg raising group and 24 patients in the ephedrine group. The correlation coefficient between stroke volume (SV) and TAPSE by M mode, speckle tracking, and tissue tracking was 0.48, 0.44, and 0.09, respectively. There was a significant increase in SV following each intervention; however, the changes in TAPSE by any method and velocity were not large enough to reach statistical significance., Conclusion: Tricuspid annular plane systolic excursion by M mode and by speckle tracking correlates modestly with SV. There was no correlation between TAPSE and SV by tissue tracking at the inferior wall of the right ventricle. Tricuspid annular plane systolic excursion by M mode and by speckle tracking does not track changes in SV following either volume loading or ephedrine administration.

Objective: To compare the different effects in fetus and puerpera with an equivalent dose of ephedrine (E) and phenylephrine (Ph) for maintaining maternal blood pressure near baseline during spinal anesthesia for a cesarean delivery., Methods: Ninety mature parturient women with single-embryo scheduled for an elective cesarean delivery under spinal anesthesia at our hospital during January-June 2010 were randomly divided into 3 groups (E, E + Ph and Ph, n = 30 each). Group E received an infusion of ephedrine (ephedrine 4 g/L), Group E + Ph ephedrine plus phenylephrine (ephedrine 2 g/L + phenylephrine 25 mg/L) and Group Ph phenylephrine (phenylephrine 50 mg/L). The blood pressure was maintained near baseline by adjusting the infusion rate during anesthesia. The maternal blood pressure, heart rate and fetal heart rate were measured at the time points of 1, 3, 5 and 10 min, skin incision and uterine incision after injecting anesthetic into subarachnoid space. Immediately after delivery, maternal arterial, umbilical arterial and umbilical venous blood samples were withdrawn for the measurements of blood gases and plasma concentrations of lactate and glucose., Results: The fetal heart rate of groups E and E + Ph significantly increased after infusion [5 min: (150 ± 10) times/min vs (142 ± 13) times/min, (146 ± 10) times/min vs (142 ± 9) times/min, both P < 0.05] while those of group Ph had no significant changes [5 min: (143 ± 9) times/min vs(143 ± 6) times/min, P > 0.05]. The incidence of fetal tachycardia in groups E and E + Ph was greater than that in group Ph. In group E, umbilical arterial and umbilical venous pH and base excess were lower than those in groups E + Ph and Ph [umbilical arterial: 7.20 ± 0.10 vs 7.27 ± 0.05, 7.28 ± 0.03, (-3.1 ± 3.1) mmol/L vs (-0.9 ± 1.7) mmol/L, (-0.3 ± 1.7) mmol/L, umbilical venous:7.29 ± 0.09 vs 7.34 ± 0.03, 7.34 ± 0.03, (-3.3 ± 2.9) mmol/L vs (-2.0 ± 1.7) mmol/L, (-0.9 ± 1.5) mmol/L, all P < 0.05]. Umbilical arterial PCO2 and plasma concentrations of lactate and glucose in group E were greater than those in group Ph (all P < 0.05). Umbilical arterial and umbilical venous plasma concentrations of lactate and glucose were greater in group E + Ph than those in group Ph (all P < 0.05). But base excess was lower (P < 0.05)., Conclusion: Phenylephrine may be more ideal for treating the hypotension of spinal anesthesia for a cesarean delivery. It corrects hypotension following spinal anesthesia, improves fetal oxygen supply and demand balance but induces no metabolic excitation in fetus as compared with ephedrine.

Background: How phenylephrine and ephedrine treatments affect global and regional haemodynamics is of major clinical relevance. Cerebral tissue oxygen saturation (Sct(O2) )-guided management may improve postoperative outcome. The physiological variables responsible for Sct(O2) changes induced by phenylephrine and ephedrine bolus treatment in anaesthetized patients need to be defined., Methods: A randomized two-treatment cross-over trial was conducted: one bolus dose of phenylephrine (100-200 µg) and one bolus dose of ephedrine (5-20 mg) were given to 29 ASA I-III patients anaesthetized with propofol and remifentanil. , mean arterial pressure (MAP), cardiac output (CO), and other physiological variables were recorded before and after treatments. The associations of changes were analysed using linear-mixed models., Results: The CO decreased significantly after phenylephrine treatment [▵CO = -2.1 (1.4) litre min(-1), P<0.001], but was preserved after ephedrine treatment [▵CO = 0.5 (1.4) litre min(-1), P>0.05]. The was significantly decreased after phenylephrine treatment [▵ = -3.2 (3.0)%, P<0.01] but preserved after ephedrine treatment [▵ = 0.04 (1.9)%, P>0.05]. CO was identified to have the most significant association with (P<0.001). After taking CO into consideration, the other physiological variables, including MAP, were not significantly associated with (P>0.05)., Conclusions: Associated with changes in CO, decreased after phenylephrine treatment, but remained unchanged after ephedrine treatment. The significant correlation between CO and implies a cause-effect relationship between global and regional haemodynamics.

Objective: To compare the behavioral effects of psychoactive drugs between two strains of mice., Methods: The Kunming (KM) and ICR mice were injected intraperitoneally with caffeine (3, 10, 30, 100 mg/kg), ephedrine (3, 10, 30, 100 mg/kg), diazepam (1, 3,1 0 mg/kg) and chloral hydrate (10, 30, 100 mg/kg), respectively. Ten min after injection, the locomotor activity in the open field was recorded for 2 h. The total distance, the distance ratio to total distance and the time in central region were analyzed for each drugs. Thirty min after injection, the latent time in the passive avoidance test was measured in a shuttle box., Results: Caffeine and diazepam prolonged the latent time, and ephedrine and chloral hydrate decreased the latent time, but there were no differences between the two strains. The two strains of mice exhibited significant differences in the total distance after injection of ephedrine 10 mg/kg, diazepam 3 mg/kg and chloral hydrate 100 mg/kg. Compared to KM mice, ICR mice exhibited an increase in the distance ratio and the time in central region after injection of ephedrine 10-100 mg/kg, but a decrease after diazepam 3-10 mg/kg., Conclusion: KM and ICR mice show no differences in latent time, but significant differences in the total distance, the distance ratio and the time in central region in the locomotor activity. Therefore, selection of mouse strains is important in the study of psychoactive drugs.

Background: Previous work demonstrated that maternal haplotypes of the β₂-adrenoceptor gene (ADRB2) influence ephedrine requirements during cesarean delivery. The use of ephedrine versus a pure α-adrenergic agonist such as phenylephrine has been associated with lower umbilical artery (UA) pH, thought to be secondary to increased fetal metabolism. There are no data evaluating the effect of fetal/neonatal genotypes on the metabolic response to maternally administered vasopressors. We hypothesized that neonatal ADRB2 genotype would affect the extent of neonatal acidemia. We also examined the effect of maternal ADRB2 and the endothelial nitric oxide synthase gene (NOS3) on ephedrine and phenylephrine requirements for treatment of maternal hypotension., Methods: The study was performed on 104 Chinese women scheduled for cesarean delivery under spinal anesthesia who were participating in a double-blind randomized clinical trial evaluating the maternal and neonatal effects of ephedrine versus phenylephrine infusions. Blood samples were drawn from the UA, umbilical vein, and maternal radial artery to measure blood gas values and lactate, ephedrine, and phenylephrine concentrations, and to determine maternal and neonatal genotype at nonsynonymous single nucleotide polymorphisms at codons 16 (rs1042713) and 27 (rs1042714) of ADRB2 and codon 298 (rs1799983) of NOS. Clinical variables (UA pH, UA lactate, and dose of vasopressors) among genotypes were compared, and regression models were created to assess the effect of genotype on vasopressor dose and fetal acid-base status., Results: Maternal ADRB2 genotype did not affect the ephedrine dose. Neonatal genotype at codon 16 influenced fetal acid-base status. UA pH was higher in Arg16 homozygous neonates (7.31 ± 0.03 in p.16Arg/Arg vs. 7.25 ± 0.11 in p.16 Arg/Gly and p.16 Gly/Gly; P < 0.001, 95%confidence interval (CI) of difference 0.03 ~ 0.09) and UA lactate was lower (2.67 mmol/L ± 0.99 in p.16Arg/Arg vs 4.28 mmol/L ± 2.79 in. p.16 Arg/Gly and p.16 Gly/Gly; P < 0.001, 95% CI of difference -2.40 ~ -0.82). In neonates born to mothers receiving ephedrine, the magnitude of the difference among genotypes was even greater (pH 7.30 ± 0.02 in p.16Arg/Arg vs. 7.19 ± 0.10 in p.16 Arg/Gly and p.16 Gly/Gly; P < 0.001, 95% CI of difference 0.07 ~ 0.14) and UA lactate was lower (3.66 mmol/L ± 1.30 in p.16Arg/Arg vs. 5.79 mmol/L ± 2.88 in p.16 Arg/Gly and p.16 Gly/Gly; P = 0.003, 95% CI of difference -3.48 ~ -0.80). In a multiple linear regression model (R² = 63.6%; P = 0.03), neonatal ADRB2 genotypes (p.16Arg/Arg and p.27Gln/Glu) and lower neonatal birth weight predicted lower UA lactate concentrations. Phenylephrine dose was not affected by maternal ADRB2 or NOS3 genotypes, and neonatal NOS3 genotype did not affect UA pH or UA lactate., Conclusion: In contrast to previous findings in a North American cohort, maternal ADRB2 genotype did not affect ephedrine requirements during elective cesarean delivery in a Chinese cohort. However, our findings suggest that neonatal ADRB2 p.Arg16 homozygosity confers a protective effect against developing ephedrine-induced fetal acidemia.

Purpose: We previously showed that compression of the nondependent lung during one-lung ventilation (OLV) in patients undergoing esophagectomy improves arterial oxygenation but impairs cardiac output (CO) and systemic oxygen delivery (DO(2)). The objective of this study was to test the hypothesis that the combination of nondependent lung compression and ephedrine improves arterial oxygenation without compromising DO(2)., Methods: Twenty patients undergoing esophagectomy through a right thoracotomy were studied. Under general anesthesia, a left-sided double-lumen tube was placed, and the dependent lung was mechanically ventilated with a tidal volume of 8 ml/kg and a fraction of inspiratory oxygen of 0.8 during OLV. When nondependent lung was compressed by surgeons to improve surgical exposure, a randomly determined intravenous bolus of either ephedrine 4 mg (group E) or an identical volume of saline (group S) was administered. Arterial blood was sampled during two-lung ventilation (TLV), at 10 min of OLV (OLV1), and 5 min after nondependent lung compression (OLV2)., Results: The initiation of OLV resulted in a significant drop in PaO(2) at OLV1 (group E, 136 ± 69 mmHg; group S, 138 ± 83 mmHg; P < 0.01) compared with TLV (group E, 404 ± 44 mmHg; group S; 367 ± 51 mmHg) and tended to improve at OLV2 (group E, 170 ± 63 mmHg; group S; 196 ± 121 mmHg). However, although CO and DO(2) significantly decreased in group S at OLV2 (4.0 ± 0.8 l/min, 621 ± 116 ml/min; P < 0.01) compared with OLV1 (5.1 ± 0.7 l/min, 811 ± 140 ml/min), there was no significant difference in these parameters in group E for the two time points., Conclusion: Although arterial oxygenation was not significantly improved by the nondependent lung compression, the addition of intravenous ephedrine to nondependent lung compression prevented the decrease in systemic oxygen delivery without deterioration of arterial oxygenation during OLV in patients undergoing esophagectomy.

Objectives: Dexmedetomidine, a highly selective alpha-2-adrenoceptor agonist, was recently introduced into clinical practice for its sedative and analgesic properties. The purpose of this study was to evaluate whether the psychostimulant drug ephedrine has any effect on dexmedetomidine-induced antinociception and locomotor inhibitor activity in mice in acute application., Methods: In both sexes of swiss albino mice; antinociception was assessed with hot-plate test and the locomotor, exploratory activities were assessed with holed open field test. The animals were received; saline + saline, ephedrine (10 mg/kg) + saline, saline + dexmedetomidine (15 μg/kg) and ephedrine (10 mg/kg) + dexmedetomidine (15 μg/kg), intraperitoneally, 30 min before hot plate or holed open field tests., Results: In the hot plate test in mice, co-administration of 15 μg/kg dexmedetomidine with 10 mg/kg ephedrine intraperitoneally not only enhanced, but also prolonged the duration of antinociception induced by dexmedetomidine. At the same time, the locomotor inhibitory effect of dexmedetomidine was counteracted by ephedrine., Conclusion: We concluded that the combined administration of dexmedetomidine with ephedrine may have beneficial effects in the treatment of pain without causing sedation, which limits the use of dexmedetomidine as an analgesic in humans.

Study Objective: To determine whether low-dose ephedrine plus priming with low-dose cisatracurium improves intubating conditions., Design: Prospective, randomized, double-blinded study., Setting: Operating room., Patients: 124 ASA physical status I and II patients scheduled for elective surgery., Interventions: Patients were randomly assigned to 4 groups (n = 31): Group PE (priming + ephedrine), Group P (priming), Group E (ephedrine), and Group NPE (no priming, no ephedrine). All patients were induced with propofol two mg/kg and sulfentanil 0.15 μg/kg. In the priming groups, 0.005 mg/kg (10% ED(95)) cisatracurium was given, followed three minutes later by 0.145 mg/kg of cisatracurium. In Groups E and NPE, a single dose of 0.15 mg/kg cisatracurium was given. Intravenous ephedrine 70 μg/kg was given in Groups PE and E. Tracheal intubation was attempted 60 seconds after the intubating dose of cisatracurium and was considered successful only if performed within 20 seconds., Measurements: Intubating conditions were graded. Heart rate and non-invasive blood pressure, at one-minute intervals, were recorded during and 5 minutes after induction., Main Results: The tracheas of all patients in Group PE were successfully intubated within 20 seconds versus 74% in Group P, 77% in Group E, and 64% in Group NPE (P < 0.001 vs. Group PE). Intubating conditions were graded good to excellent in all PE patients, but in only 52% of Groups P and E, and 48% of NPE patients (P < 0.001). Hemodynamic variables were comparable among groups (P = ns)., Conclusions: Low-dose ephedrine plus priming with low-dose cisatracurium before an intubating dose, significantly improved clinical intubating conditions at 60 seconds., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Neuraxial anaesthesia improves tissue perfusion and tissue oxygen tension. Vasodilation induced by this technique may result in hypotension requiring the administration of vasoactive drugs. The use of peripheral vasoconstrictors might counteract the improved tissue perfusion and its potentially beneficial effects. We therefore investigated the effect of i.v. norepinephrine and ephedrine on skin perfusion using laser-Doppler flowmetry (LDF) in patients during spinal anaesthesia., Methods: Skin blood flow expressed in perfusion units (PU) provided by LDF was measured simultaneously at the foot and the manubrium levels in 44 patients during spinal anaesthesia with a sensory level below T5. Norepinephrine infusion was then titrated to normalize mean arterial pressure (MAP) in 23 patients (Group NOR). Ephedrine (max. 10 mg) was administered in 21 patients (Group EPH). Changes in relative PU were compared between the two sites of measurements in each group during drug administration. The same doses of norepinephrine were assessed in 11 normal volunteers to assure comparable vasoreactivity at the foot and manubrium levels., Results: Spinal anaesthesia resulted in a 10% decrease in MAP (P<0.001), an increase in relative PU values at the foot level (P<0.001), and a decrease at the sternum level (P<0.05). Norepinephrine and ephedrine produced a significant increase in relative PU values at the foot level when compared with the sternum level (NOR: P=0.02; EPH: P=0.0035). In volunteers, norepinephrine decreased cutaneous perfusion similarly at the manubrium and foot levels., Conclusions: Improved skin perfusion induced by spinal anaesthesia was not counteracted by the use of norepinephrine or ephedrine.