Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensit...Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.展开更多
BACKGROUND: It has been proved by many experimental studies from the aspects of morphology and immunocytochemistry in recent years that bone marrow stromal cells (BMSCs) can in vitro induce and differentiate into the ...BACKGROUND: It has been proved by many experimental studies from the aspects of morphology and immunocytochemistry in recent years that bone marrow stromal cells (BMSCs) can in vitro induce and differentiate into the cells possessing the properties of nerve cells. But the functions of BMSCs-derived neural stem cells(NSCs) and the differentiated neuron-like cells are still unclear. OBJECTIVE: To observe whether bone marrow-derived NSCs can secrete norepinephrine (NE) under the condition of in vitro culture, induce and differentiation, and analyze the biochemical properties of BMSCs-derived NSCs. DESIGN: A non-randomized and controlled experimental observation. SETTING: Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. MATERIALS: This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5- month-old healthy New Zealand white rabbits. METHODS: This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5 month-old healthy New Zealand white rabbits. BMSCs of rabbits were isolated and performed in vitro culture, induce and differentiation with culture medium of NSCs and differentiation-inducing factor, then identified with immunocytochemical method. Experimental grouping: ①Negative control group: L-02 hepatic cell and RPMI1640 culture medium were used. ② Background culture group: Only culture medium of NSCs as culture solution was added into BMSCs to perform culture, and 0.1 volume fraction of imported fetal bovine serum was supplemented 72 hours later. ③Differentiation inducing factor group: After culture for 72 hours, retinoic acid and glial cell line-derived neurotrophic factors were added in the culture medium of BMSCs and NSCs as corresponding inducing factors. The level of NE in each group was detected on the day of culture and 5, 7, 14 and 20 days after culture with high performance liquid chromatography(HPLC). The procedure was conducted 3 times in each group.Standard working curve was made according to the corresponding relationship of NE concentration and peak area. The concentration of NE every 1×107 cells was calculated according to standard curve and cell counting. MAIN OUTCOME MEASURES: The level of NE of cultured cells was detected with HPLC; immunocytochemistrical identification of Nestin and neuron specific nuclear protein was performed. RESULTS: ① On the 14th day after cell culture, BMSCs turned into magnus and round cells which presented Nestin-positive antigen, then changed into neuron-like cells with long processus and presented neuron specific nuclear protein -positive antigen at the 20th day following culture. ② The ratio of NE concentration and peak area has good linear relationship, and regression equation was Y=1.168 36+0.000 272 8X,r=0.998 4.Coefficient variation (CV) was < 5% and the recovery rate was 92.39%(Y referred to concentration and X was peak area).③NE was well detached within 10 minutes under the condition of this experiment. ④ NE was detected in NSCs and their culture mediums, which were cultured for 7, 14 and 20 days respectively, but no NE in BMSCs, NSCs-free culture medium and L-02 hepatic cell which were as negative control under the HPLC examination. Analysis of variance showed that the level of NE gradually increased following the elongation of culture time (P < 0.01). No significant difference in the level of NE existed at the same time between differentiation inducing factor group and basic culture group(P > 0.05). CONCLUSION: BMSCs of rabbits can proliferate in vitro and express Nestin antigen; They can differentiate into neuron-like cells, express specific neucleoprotein of mature neurons, synthesize and secrete NE as a kind of neurotransmitter.展开更多
Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception...Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I2 statistic, we used a fixed effects model(P≥0.1) and expressed the results as risk ratios(RRs) for dichotomous outcomes or as standardized mean differences(SMDs) for continuous data with 95% confidence intervals(CIs). Meta-analysis was conducted using Review Manager 5.1 software.Results: Seven trials(n=2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2%(840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin(RR 1.07; 95%CI 0.97-1.20; P=0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate(HR)(SMD 0.21; 95%CI-0.08-0.50; P=0.15), mean arterial pressure(MAP)(SMD 0.15; 95%CI-0.15-0.44; P=0.33), cardiac index(CI)(SMD-0.10; 95%CI-0.64-0.44; P=0.73), systemic vascular resistance index(SVRI)(SMD 0.15; 95%CI-0.39-0.70; P=0.58), oxygen delivery(DO2)(SMD-0.06; 95%CI-0.62-0.49; P=0.82), oxygen consumption(VO2)(SMD 0.03; 95%CI-0.52-0.59; P=0.91) or lactic acid(SMD 0.07; 95%CI-0.23-0.36; P=0.66). No significant heterogeneity was found in these comparisons(P≥0.1).Conclusions: There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.展开更多
The current survival sepsis guideline proposes the use of vasopressors and fluid resuscitation to maintain the mean arterial pressure (MAP) ≥ 65 mmHg. Titrating catecholamine infusion to achieve higher MAP has been d...The current survival sepsis guideline proposes the use of vasopressors and fluid resuscitation to maintain the mean arterial pressure (MAP) ≥ 65 mmHg. Titrating catecholamine infusion to achieve higher MAP has been demonstrated to improve tissue oxygenation, microcirculation, renal function and overall outcome of the patient in some studies and literature on actual hemodynamic goals is scarce. AIM: To study the influence of two MAP on tissue oxygenation and perfusion parameters in patients of septic shock on norepinephrine infusion. SUBJECT AND MATERIALS: Forty adult patients with the diagnosis of septic shock were enrolled. In all patients norepinephrine was titrated to first stabilize the MAP at 65 ± 5 mmHg (Set I), followed by MAP of 85 ± 5 mmHg (Set II). Heart rate (HR), Central venous oxygen saturation (SCVO2), Transcutaneous partial pressure of oxygen (PtcO2) by TCM 400/TINA (using miniature Clark electrode), Arterial partial pressure of oxygen(PaO2), PtO2/PaO2 ratio, Urine output and Serum Base deficit were recorded in each Set after 2 hrs of stabilization. RESULTS: There was a significant increase in transcutaneous partial pressure of oxygen PtcO2 (p tO2/PaO2 (p < 0.0001), ScvO2 (p < 0.0001), urine output (p < 0.006) on increasing the MAP from 65mmHg to 85mmHg. Serum base deficit also improved (p < 0.0001). CONCLUSION: Higher MAP with norepinephrine is associated with better perfusion, oxygenation parameters in patients with established septic shock. These findings suggest that there is improvement in tissue oxygenation parameters using escalating doses of norepinephrine to achieve higher MAP without inherent adverse展开更多
Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been ...Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been fully determined. The objective of this trial was to determine the effect of melatonin on blood pressure morning increase and a peripheral vasoconstriction challenge in healthy volunteers. Twelve healthy male volunteers were included in a prospective, comparative, randomized, crossover trial in which changes on blood pressure (BP) and heart rate (HR) after the first morning orthostatism and endovenous norepinephrine (NE) infusion were measured one hour after the administration of placebo (PL) or 10 mg of melatonin in double blind conditions. Melatonin blunted the effects of the first orthostatism on BP and HR. Melatonin also reduces the pressor effect of NA. One concludes that melatonin has central and peripheral hypotensive effects that support a potential role of this hormone in cardiovascular therapeutics.展开更多
Norepinephrine(NE;also known as noradrenaline)is the body’s primary adrenergic neurotransmitter which belongs to the catecholamine family.Norepinephrine has pharmacologic effects on theα1(Suita et al.,2015),α2(Schw...Norepinephrine(NE;also known as noradrenaline)is the body’s primary adrenergic neurotransmitter which belongs to the catecholamine family.Norepinephrine has pharmacologic effects on theα1(Suita et al.,2015),α2(Schwartz,1997),β1,β2 andβ3(Tsukada et al.,2003)adrenoceptors.In the brain,norepinephrine increases arousal and alertness,promotes vigilance,enhances formation and retrieval of memory,and focuses attention.It also increases restlessness and anxiety.In the remainder of the body,norepinephrine increases heart rate and blood pressure,triggers the release of glucose from energy stores,increases blood flow to skeletal muscle and increases muscle contraction,reduces blood flow to the gastrointestinal system and its motility and lastly,inhibits voiding of the bladder(Goldstein,2010).This last point is particularly interesting in the context of this perspective piece.展开更多
The relationship between 5-HT receptor and α-adrenoceptor was investigated inrat medullary slice preparations.In 57 nucleus tractus solitarii(NTS)neurons,47(82.5%)responded to both serotonin(5-HT)and norepinephrine(N...The relationship between 5-HT receptor and α-adrenoceptor was investigated inrat medullary slice preparations.In 57 nucleus tractus solitarii(NTS)neurons,47(82.5%)responded to both serotonin(5-HT)and norepinephrine(NE).After synapse transmissionwas blocked by perfusion of artificial cerebrospinal fluid(ACSF)with low calcium andhigh magnesium,5 in 8 neurons were still sensitive to both 5-HT and NE.On the otherhand,3 in 5 neurons responding only to 5-HT or NA were sensitive to both 5-HT andNE after the synapse transmission blockage.In some neurons which exhibited excitatoryor inhibitory responses to 5-HT or NE alone,the responses were inversed when perfusedwith 5-HT and NE in combination.These results suggest that there may exist aninhibitory interaction between 5-HT receptors and α-adrenoceptors in NTS and that most5-HT and α-adrenoceptors coexist in the same NTS neurons.展开更多
The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group wer...The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group were perfused with modified Krebs-Henseleit buffer containing different concentrations of testosterone (0.1,1.0,10.0,and 100.0 nmol/L,respectively).Myocardial ischemia was induced by globally stopping the perfusion flow.Exocytotic norepinephrine release was induced by electrical field stimulation at 5 V (effective voltage) and 6 Hz (pulse width of 2 ms) for 1 min.The overflow of norepinephrine was determined by high pressure liquid chromatography and electrochemical detec-tion (HPLC-EC).Following acute ischemia,testosterone (1.0,10.0 and 100.0 nmol/L) significantly re-duced norepinephrine release (P<0.01),and the norepinepherine overflow was similar between the con-trol and 0.1 nmol/L testosterone group (P>0.05).Electrical stimulation of the ventricle evoked norepi-nepherine release,and this was diminished by the perfusion with testosterone at the concentrations of 1.0,10.0 and 100.0 nmol/L (P<0.01).It is suggested that testosterone suppresses ischemia-and electri-cal stimulationinduced norepinepherine release in the isolated rat hearts.展开更多
Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the additio...Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.展开更多
Objective The aim of this study was to explore the effect of norepinephrine(NE)on renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis.Methods Atherosclerosis was induced in...Objective The aim of this study was to explore the effect of norepinephrine(NE)on renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis.Methods Atherosclerosis was induced in 21 New Zealand white rabbits by feeding them a cholesterol-rich diet for 16 weeks.Thirteen healthy New Zealand white rabbits were randomly selected as controls.After atherosclerosis induction,standard ultrasonography was performed to confirm that there was no plaque or accelerated flow at the origin of the renal artery.Contrast-enhanced ultrasound(CEUS)was performed at baseline and during intravenous injection of NE.The degree of contrast enhancement of renal cortex and medulla after the injection of contrast agents was quantified by calculating the enhanced intensity.Results The serum nitric oxide(NO)level in atherosclerotic rabbits was higher than that in healthy rabbits(299.6±152 vs.136.5±49.5,P<0.001).The infusion of NE induced a significant increase in the systolic blood pressure(112±14 mmHg vs.84±9 mmHg,P=0.016)and a significant decrease in the enhanced intensity in renal cortex(17.78±2.07 dB vs.21.19±2.03 dB,P<0.001)and renal medulla(14.87±1.82 dB vs.17.14±1.89 dB,P<0.001)during CEUS.However,the enhanced intensity in the cortex and medulla of healthy rabbits after NE infusion showed no significant difference from that at baseline.Conclusion NE may reduce renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis,partly by reducing the serum NO level.展开更多
BACKGROUND Bleeding in the gastrointestinal tract is common and transarterial embolization enables the clinician to control gastrointestinal bleeding.Contrast extravasation is a prerequisite for successful embolizatio...BACKGROUND Bleeding in the gastrointestinal tract is common and transarterial embolization enables the clinician to control gastrointestinal bleeding.Contrast extravasation is a prerequisite for successful embolization.Provocative angiography is helpful in the detection of elusive bleeding.AIM We performed a retrospective analysis of angiographic treatment in patients with lower gastrointestinal hemorrhage and initially negative angiographies,as well as the role of norepinephrine(NE)in unmasking bleeding.METHODS We analyzed 41 patients with lower gastrointestinal bleeding after angiography who had undergone treatment over a period of 10 years.All patients had a positive shock index and needed intensive care.RESULTS In three of four patients,angiography disclosed the site of bleeding when NE was used during the procedure for hemodynamic stabilization.CONCLUSION We suggest that angiography performed after the administration of NE in unstable patients with gastrointestinal bleeding and an initially negative angiography has the potential to unmask bleeding sites for successful embolization.However,this statement must be confirmed in prospective studies.展开更多
BACKGROUND: Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotect...BACKGROUND: Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotective effects. OBJECTIVE: To observe the effect of 17 beta-estradiol on the content of norepinephrine (NE) and level of tumor necrosis factor (TNF) in submandibular glands of rats with sympathetic nerve injury, and analyze the dose-dependence and pathway of action. DESIGN: A randomized control animal study.SETTINGS: Department of Hand Surgery, the 252 Hospital of Chinese PLA; Department of Hand Surgery, Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: Fifty healthy female Wistar rats were randomly divided into 5 groups with 10 rats in each group: sham-operated group, ovariectomy+6-OHDA+saline group, ovariectomy+6-OHDA+17β-estradiol 50, 200 and 500 μg/kg groups. METHODS: The experiments were carried out in Tongji Medical College, Huazhong University of Science and Technology between October 2005 and March 2006. Bilateral ovaries were only exposed but not resected for the rats in the sham-operated group, but bilateral ovaries were resected in all the other groups. In the ovariectomy+6-OHDA+17β-estradiol 50, 200 and 500 μg/kg groups, the rats were administrated with intraperitoneal injection of 6-OHDA (8 mg/kg), and then immediately given 17β-estradiol of corresponding dosages respectively, once a day for 10 days continuously. Rats in the sham-operated group and ovariectomy+6-OHDA+saline group were administrated with saline of the same volume. After administration, 5 rats in each group were killed to determine the NE contents in bilateral submandibular glands with high performance liquid chromatography-electrochemical detector (HPLC-ECD), and the other 5 rats were used to determine the TNF levels in submandibular glands with enzyme-linked immunosorbant assay.MAIN OUTCOME MEASURES: The NE contents and TNF levels in submandibular glands of rats in each group were observed. RESULTS: All the 50 rats were involved in the analysis of results. ① The NE content was obviously lower in the ovariectomy+6-OHDA+saline group than in the sham-operated group [(1 035±196), (1 823±314) ng/g, P < 0.05], there were no significant differences between the ovariectomy+6-OHDA+17β-estradiol 50 μg/kg group and ovariectomy+6-OHDA+saline group [(1 004±253), (1 035±196) ng/g, P > 0.05], but obviously higher in the ovariectomy+6-OHDA+17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy+6-OHDA+saline group [(1 487±268), (1 939±274), (1 035±196) ng/g, P < 0.05]. ② The TNF level was obviously higher in the ovariectomy+6-OHDA+saline group than in the sham-operated group [(3.498±0.792), (1.893±0.533) ng/g, P < 0.05], there were no significant differences between the ovariectomy+ 6-OHDA+17β-estradiol 50 μg/kg group and ovariectomy+6-OHDA+saline group [(3.328±0.712), (3.498±0.792) ng/g, P > 0.05], but obviously lower in the ovariectomy+6-OHDA+17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy+6-OHDA+saline group [(2.639±0.438), (2.016±0.619), (3.498±0.792) ng/g, P < 0.05]. CONCLUSION: Estrogen has obvious protective effect dose-dependently on 6-OHDA induced chemical sympathetic nerve terminal injury in rats, and it may play its protective role by reducing TNF level and ameliorating inflammatory reaction.展开更多
The primary neurotransmitters targeted by currently used antidepressants, such as duloxetine, venlafaxine and fluoxetine, are serotonin and norepinephrine, which also are released in significant amounts in the central...The primary neurotransmitters targeted by currently used antidepressants, such as duloxetine, venlafaxine and fluoxetine, are serotonin and norepinephrine, which also are released in significant amounts in the central nervous system in response to sympathetic nervous system activation. In cultured hippocampal neurons, we have previously shown that norepinephrine induces increased expression of brain-derived neurotrophic factor (BDNF), the PI-3 K/Akt, MAPK pro-survival pathways, the BDNF receptor, TrkB, a transcription factor, and cyclic AMP response element binding protein (CREB). In the present study, we extend these findings of increased BDNF expression to its kinetics of release into the surrounding media. We also evaluate these two cell survival pathways, TrkB and CREB, in response to application of serotonin and/or norepinephrine. Serotonin elicits an earlier, but brief expression and release of BDNF, whereas norepinephrine elicits a more delayed and sustained release of BDNF. In response to both norepinephrine and 5-HT, the presence of BDNF in lysates and subsequent release into the media is significantly increased out to 4 h, as is PI-3 K/Akt activation. Together, these two neurotransmitters increase BDNF expression and release covering the entire 8 h continuum evaluated. The results of this study provide further evidence for a G protein-coupled receptor and a crosstalk-to-TrkB receptor with transactivation signaling across pathways.展开更多
Objective: To compare the preventive effect of ephedrine, phenylephrine and norepinephrine on hypotension after lumbar anesthesia in cesarean section and their effects on newborns. Methods: 25 cesarean section women i...Objective: To compare the preventive effect of ephedrine, phenylephrine and norepinephrine on hypotension after lumbar anesthesia in cesarean section and their effects on newborns. Methods: 25 cesarean section women in our hospital from December 2016 to January 2018 were selected and divided into three groups according to different surgical medication, namely, ephedrine group (n=40), phenylephrine group (n=45) and norepinephrine group (n=40). Then the vital signs, neonatal blood gas analysis, neonatal Apgar score, adverse reactions of the three groups were compared. Results: The HR at T0~T3, and SBP and DBP at T0 and T1 had no difference among three groups (P>0.05). The HR, SBP and DBP at T3 ranking in a descending order was norepinephrine group, ephedrine group and phenylephrine group (P<0.05). The PCO2 and PO2 had no difference among three groups (P>0.05). The pH ranking in a descending order was norepinephrine group, ephedrine group and phenylephrine group (P<0.05). The SpO2 ranking in a descending order was phenylephrine group, ephedrine group and norepinephrine group (P<0.05). The Apgar score at birth in ephedrine group and norepinephrine group was significantly lower than that in phenylephrine group (P<0.05), while the Apgar score at post-birth 5 min and 10 min had no difference among three groups (P>0.05). The incidence of hypertension, gastrointestinal reaction, hyperhidrosis and palpitation in the phenylephrine group was significantly lower than that in the norepinephrine group (P<0.05). Conclusion: The phenylephrine and norepinephrine have no difference on the preventive effect of hypotension after spinal anesthesia in cesarean section, while safety of norepinephrine for puerpera and neonates is higher.展开更多
Objective:To observe the effect of continuous hemofiltration combined with norepinephrine in the treatment of septic shock,and to explore the value of blood purification in the treatment of septic shock.Methods:From N...Objective:To observe the effect of continuous hemofiltration combined with norepinephrine in the treatment of septic shock,and to explore the value of blood purification in the treatment of septic shock.Methods:From November 2018 to December 2020,100 patients with septic shock in the Intensive care unit of our hospital were selected and randomly divided into observation group and control group,with 50 cases in each group.The control group was given conventional treatment,while the observation group was given continuous hemofiltration combined with norepinephrine intervention.The clinical efficacy,Scv02,MAP and oxygenation index(PO_(2)/FiO_(2))of the two groups were compared.The levels of interleukin-6(IL-6),procalcitonin(PCT)and the total number of leukocytes and other inflammatory factors were compared 72 hours after treatment,and the 28-day mortality of the two groups was counted.Results:The total effective rate of the observation group(92.00%)was significantly higher than that of the control group(86.00%),the difference was statistically significant(p<0.05);the 28-day mortality of the two groups was 8.00%in the observation group and 14.00%in the control group,the difference was statistically significant(χ^(2)=4.629,p=0.038);Before treatment,the Scv02,MAP and PO_(2)/FiO_(2)levels of the two groups were significantly higher than those of post-therapy.There was no significant difference between the two groups(p>0.05);After 48 hours of treatment,the levels of Scv02,MAP and PO_(2)/FiO_(2)in the two groups were significantly increased,while the levels of scv02,map,PO_(2)/FiO_(2)in the observation group were more significantly increased than those in the control group(p<0.05);Before treatment,the levels of IL-6,PCT and total white blood cells in the two groups were significantly higher than those of post-therapy(p<0.05)After 72 hours of treatment,the levels of IL-6,PCT and the total number of white blood cells in the two groups decreased significantly,while the levels of IL-6,PCT and the total number of white blood cells in the observation group decreased more significantly than those in the control group(p<0.05).Conclusion:Continuous blood purification combined with norepinephrine can effectively reduce the level of serum inflammatory factors in patients with septic shock,improve hemodynamic indexes,improve survival rate,which is worthy of clinical application.展开更多
Background The benefits of early use of norepinephrine in endotoxemic shock remain unknown.We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically rel...Background The benefits of early use of norepinephrine in endotoxemic shock remain unknown.We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically relevant large animal model.Methods Vasodilatory shock was induced by endotoxin bolus in 30 Bama suckling pigs.Treatment included fluid resuscitation and administration of different doses of norepinephrine,to induce return to baseline mean arterial pressure(MAP).Fluid management,hemodynamic,microcirculation,inflammation,and organ function variables were monitored.All animals were supported for 6 h after endotoxemic shock.Results Infused fluid volume decreased with increasing norepinephrine dose.Return to baseline MAP was achieved more frequently with doses of 0.8µg/kg/min and 1.6µg/kg/min(P<0.01).At the end of the shock resuscitation period,cardiac index was higher in pigs treated with 0.8µg/kg/min norepinephrine(P<0.01),while systemic vascular resistance was higher in those receiving 0.4µg/kg/min(P<0.01).Extravascular lung water level and degree of organ edema were higher in animals administered no or 0.2µg/kg/min norepinephrine(P<0.01),while the percentage of perfused small vessel density(PSVD)was higher in those receiving 0.8µg/kg/min(P<0.05)and serum lactate was higher in the groups administered no and 1.6µg/kg/min norepinephrine(P<0.01).Conclusions The impact of norepinephrine on the macro-and micro-circulation in early-stage endotoxemic shock is dose-dependent,with very low and very high doses resulting in detrimental effects.Only an appropriate norepinephrine dose was associated with improved tissue perfusion and organ function.展开更多
Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in ...Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals.Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons.Astrocytes,outnumbering neurons by nearly fivefold,support and regulate neuronal and synaptic function.Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling.This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep,wakefulness,and arousal levels,exploring the involvement of noradrenaline signaling,ion channels,and glutamatergic signaling in different cortical states.These findings highlight the significant impact of astrocytes on large-scale neuronal networks,influencing brain activity and responsiveness.Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation.More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states,requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep-and arousal-related disorders.展开更多
Background:In recent years,norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia.Intermittent bolus is a widely used admin...Background:In recent years,norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia.Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China.Thus,in this randomized,double-blinded study,we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension.Methods:In a tertiary women’s hospital in Nanjing,China,102 women were allocated with computer derived randomized number to receive prophylactic 8 mg norepinephrine(group N;n=52)or 100 mg phenylephrine(group P;n=50)immediately post-spinal anesthesia,followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80%of the baseline.Our primary outcome was standardized maternal cardiac output(CO)reading from spinal anesthesia until delivery analyzed by a two-step method.Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes.Maternal side effects and neonatal outcomes were collected as well.Results:Compared to group P,women in groupNhad a higherCO(standardizedCO5.8±0.9 vs.5.3±1.0 L/min,t=2.37,P=0.02)and stroke volume(SV,standardized SV 73.6±17.2 vs.60.0±13.3 mL,t=4.52,P<0.001),and a lower total peripheral resistance(875±174 vs.996±182 dyne·s/cm5,t=3.44,P<0.001).Furthermore,the incidence of bradycardia was lower in group N than in group P(2%vs.14%,P=0.023),along with an overall higher standardized heart rate(78.8±11.6 vs.75.0±7.3 beats/min,P=0.049).Other hemodynamics,as well as maternal side effects and neonatal outcomes,were similar in two groups(P>0.05).Conclusions:Compared to equivalent phenylephrine,intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia;however,no obvious maternal or neonatal clinical advantages were observed for norepinephrine.展开更多
Background:The peripheral perfusion index(PI),as a real-time bedside indicator of peripheral tissue perfusion,may be useful for determining mean arterial pressure(MAP)after early resuscitation of septic shock patients...Background:The peripheral perfusion index(PI),as a real-time bedside indicator of peripheral tissue perfusion,may be useful for determining mean arterial pressure(MAP)after early resuscitation of septic shock patients.The aim of this study was to explore the response of PI to norepinephrine(NE)-induced changes in MAP.Methods:Twenty septic shock patients with pulse-induced contour cardiac output catheter,who had usual MAP under NE infusion after early resuscitation,were enrolled in this prospective,open-label study.Three MAP levels(usual MAP-10 mmHg,usual MAP,and usual MAP+10 mmHg)were obtained by NE titration,and the corresponding global hemodynamic parameters and PI were recorded.The general linear model with repeated measures was used for analysis of variance of related parameters at three MAP levels.Results:With increasing NE infusion,significant changes were found in MAP(F=502.46,P<0.001)and central venous pressure(F=27.45,P<0.001)during NE titration.However,there was not a significant and consistent change in continuous cardiac output(CO)(F=0.41,P=0.720)and PI(F=0.73,P=0.482)at different MAP levels.Of the 20 patients enrolled,seven reached the maximum PI value at usual MAP-10 mmHg,three reached the maximum PI value at usual MAP,and ten reached the maximum PI value at usual MAP+10 mmHg.The change in PI was not significantly correlated with the change in CO(r=0.260,P=0.269)from usual MAP-10 mmHg to usual MAP.There was also no significant correlation between the change in PI and change in CO(r=0.084,P=0.726)from usual MAP to usual MAP+10 mmHg.Conclusions:Differing MAP levels by NE infusion induced diverse PI responses in septic shock patients,and these PI responses may be independent of the change in CO.PI may have potential applications for MAP optimization based on changes in peripheral tissue perfusion.展开更多
Tissue concentrations of norepinephrine(NE)are markedly decreased in various regions of the Parkinson’s disease(PD)brain.As in the substantia nigra pars compacta,neuronal dropout and Lewy bodies are prominent changes...Tissue concentrations of norepinephrine(NE)are markedly decreased in various regions of the Parkinson’s disease(PD)brain.As in the substantia nigra pars compacta,neuronal dropout and Lewy bodies are prominent changes affecting the locus coeruleus,which is the source of ascending NErgic projections.Despite the major roles of NE throughout the brain,there has been only minimal exploration of pharmacological intervention with NErgic neurotransmission.Cognitive operations,“freezing”of gait,tremor,dyskinesia,REM sleep regulation,and other aspects of brain function are tied into signaling by NE,and there is also evidence that it may have a role in the neurodegenerative process itself.This article reviews the reported pharmacological experience in PD therapeutics.展开更多
文摘Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.
基金the National Natural Science Foundation of China, No. 30270491 the Natural Science Foundation of Guangdong Province, No. 04020422 Science and Technology Plan Program of Guangdong Province, No. 2003A3020304
文摘BACKGROUND: It has been proved by many experimental studies from the aspects of morphology and immunocytochemistry in recent years that bone marrow stromal cells (BMSCs) can in vitro induce and differentiate into the cells possessing the properties of nerve cells. But the functions of BMSCs-derived neural stem cells(NSCs) and the differentiated neuron-like cells are still unclear. OBJECTIVE: To observe whether bone marrow-derived NSCs can secrete norepinephrine (NE) under the condition of in vitro culture, induce and differentiation, and analyze the biochemical properties of BMSCs-derived NSCs. DESIGN: A non-randomized and controlled experimental observation. SETTING: Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. MATERIALS: This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5- month-old healthy New Zealand white rabbits. METHODS: This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5 month-old healthy New Zealand white rabbits. BMSCs of rabbits were isolated and performed in vitro culture, induce and differentiation with culture medium of NSCs and differentiation-inducing factor, then identified with immunocytochemical method. Experimental grouping: ①Negative control group: L-02 hepatic cell and RPMI1640 culture medium were used. ② Background culture group: Only culture medium of NSCs as culture solution was added into BMSCs to perform culture, and 0.1 volume fraction of imported fetal bovine serum was supplemented 72 hours later. ③Differentiation inducing factor group: After culture for 72 hours, retinoic acid and glial cell line-derived neurotrophic factors were added in the culture medium of BMSCs and NSCs as corresponding inducing factors. The level of NE in each group was detected on the day of culture and 5, 7, 14 and 20 days after culture with high performance liquid chromatography(HPLC). The procedure was conducted 3 times in each group.Standard working curve was made according to the corresponding relationship of NE concentration and peak area. The concentration of NE every 1×107 cells was calculated according to standard curve and cell counting. MAIN OUTCOME MEASURES: The level of NE of cultured cells was detected with HPLC; immunocytochemistrical identification of Nestin and neuron specific nuclear protein was performed. RESULTS: ① On the 14th day after cell culture, BMSCs turned into magnus and round cells which presented Nestin-positive antigen, then changed into neuron-like cells with long processus and presented neuron specific nuclear protein -positive antigen at the 20th day following culture. ② The ratio of NE concentration and peak area has good linear relationship, and regression equation was Y=1.168 36+0.000 272 8X,r=0.998 4.Coefficient variation (CV) was < 5% and the recovery rate was 92.39%(Y referred to concentration and X was peak area).③NE was well detached within 10 minutes under the condition of this experiment. ④ NE was detected in NSCs and their culture mediums, which were cultured for 7, 14 and 20 days respectively, but no NE in BMSCs, NSCs-free culture medium and L-02 hepatic cell which were as negative control under the HPLC examination. Analysis of variance showed that the level of NE gradually increased following the elongation of culture time (P < 0.01). No significant difference in the level of NE existed at the same time between differentiation inducing factor group and basic culture group(P > 0.05). CONCLUSION: BMSCs of rabbits can proliferate in vitro and express Nestin antigen; They can differentiate into neuron-like cells, express specific neucleoprotein of mature neurons, synthesize and secrete NE as a kind of neurotransmitter.
文摘Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I2 statistic, we used a fixed effects model(P≥0.1) and expressed the results as risk ratios(RRs) for dichotomous outcomes or as standardized mean differences(SMDs) for continuous data with 95% confidence intervals(CIs). Meta-analysis was conducted using Review Manager 5.1 software.Results: Seven trials(n=2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2%(840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin(RR 1.07; 95%CI 0.97-1.20; P=0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate(HR)(SMD 0.21; 95%CI-0.08-0.50; P=0.15), mean arterial pressure(MAP)(SMD 0.15; 95%CI-0.15-0.44; P=0.33), cardiac index(CI)(SMD-0.10; 95%CI-0.64-0.44; P=0.73), systemic vascular resistance index(SVRI)(SMD 0.15; 95%CI-0.39-0.70; P=0.58), oxygen delivery(DO2)(SMD-0.06; 95%CI-0.62-0.49; P=0.82), oxygen consumption(VO2)(SMD 0.03; 95%CI-0.52-0.59; P=0.91) or lactic acid(SMD 0.07; 95%CI-0.23-0.36; P=0.66). No significant heterogeneity was found in these comparisons(P≥0.1).Conclusions: There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.
文摘The current survival sepsis guideline proposes the use of vasopressors and fluid resuscitation to maintain the mean arterial pressure (MAP) ≥ 65 mmHg. Titrating catecholamine infusion to achieve higher MAP has been demonstrated to improve tissue oxygenation, microcirculation, renal function and overall outcome of the patient in some studies and literature on actual hemodynamic goals is scarce. AIM: To study the influence of two MAP on tissue oxygenation and perfusion parameters in patients of septic shock on norepinephrine infusion. SUBJECT AND MATERIALS: Forty adult patients with the diagnosis of septic shock were enrolled. In all patients norepinephrine was titrated to first stabilize the MAP at 65 ± 5 mmHg (Set I), followed by MAP of 85 ± 5 mmHg (Set II). Heart rate (HR), Central venous oxygen saturation (SCVO2), Transcutaneous partial pressure of oxygen (PtcO2) by TCM 400/TINA (using miniature Clark electrode), Arterial partial pressure of oxygen(PaO2), PtO2/PaO2 ratio, Urine output and Serum Base deficit were recorded in each Set after 2 hrs of stabilization. RESULTS: There was a significant increase in transcutaneous partial pressure of oxygen PtcO2 (p tO2/PaO2 (p < 0.0001), ScvO2 (p < 0.0001), urine output (p < 0.006) on increasing the MAP from 65mmHg to 85mmHg. Serum base deficit also improved (p < 0.0001). CONCLUSION: Higher MAP with norepinephrine is associated with better perfusion, oxygenation parameters in patients with established septic shock. These findings suggest that there is improvement in tissue oxygenation parameters using escalating doses of norepinephrine to achieve higher MAP without inherent adverse
文摘Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been fully determined. The objective of this trial was to determine the effect of melatonin on blood pressure morning increase and a peripheral vasoconstriction challenge in healthy volunteers. Twelve healthy male volunteers were included in a prospective, comparative, randomized, crossover trial in which changes on blood pressure (BP) and heart rate (HR) after the first morning orthostatism and endovenous norepinephrine (NE) infusion were measured one hour after the administration of placebo (PL) or 10 mg of melatonin in double blind conditions. Melatonin blunted the effects of the first orthostatism on BP and HR. Melatonin also reduces the pressor effect of NA. One concludes that melatonin has central and peripheral hypotensive effects that support a potential role of this hormone in cardiovascular therapeutics.
文摘Norepinephrine(NE;also known as noradrenaline)is the body’s primary adrenergic neurotransmitter which belongs to the catecholamine family.Norepinephrine has pharmacologic effects on theα1(Suita et al.,2015),α2(Schwartz,1997),β1,β2 andβ3(Tsukada et al.,2003)adrenoceptors.In the brain,norepinephrine increases arousal and alertness,promotes vigilance,enhances formation and retrieval of memory,and focuses attention.It also increases restlessness and anxiety.In the remainder of the body,norepinephrine increases heart rate and blood pressure,triggers the release of glucose from energy stores,increases blood flow to skeletal muscle and increases muscle contraction,reduces blood flow to the gastrointestinal system and its motility and lastly,inhibits voiding of the bladder(Goldstein,2010).This last point is particularly interesting in the context of this perspective piece.
文摘The relationship between 5-HT receptor and α-adrenoceptor was investigated inrat medullary slice preparations.In 57 nucleus tractus solitarii(NTS)neurons,47(82.5%)responded to both serotonin(5-HT)and norepinephrine(NE).After synapse transmissionwas blocked by perfusion of artificial cerebrospinal fluid(ACSF)with low calcium andhigh magnesium,5 in 8 neurons were still sensitive to both 5-HT and NE.On the otherhand,3 in 5 neurons responding only to 5-HT or NA were sensitive to both 5-HT andNE after the synapse transmission blockage.In some neurons which exhibited excitatoryor inhibitory responses to 5-HT or NE alone,the responses were inversed when perfusedwith 5-HT and NE in combination.These results suggest that there may exist aninhibitory interaction between 5-HT receptors and α-adrenoceptors in NTS and that most5-HT and α-adrenoceptors coexist in the same NTS neurons.
基金supported by grants from the National Natural Science Foundation of China (No. 30670880)the Shanghai Municipal Natural Science Foundation (No. XD1402600)
文摘The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group were perfused with modified Krebs-Henseleit buffer containing different concentrations of testosterone (0.1,1.0,10.0,and 100.0 nmol/L,respectively).Myocardial ischemia was induced by globally stopping the perfusion flow.Exocytotic norepinephrine release was induced by electrical field stimulation at 5 V (effective voltage) and 6 Hz (pulse width of 2 ms) for 1 min.The overflow of norepinephrine was determined by high pressure liquid chromatography and electrochemical detec-tion (HPLC-EC).Following acute ischemia,testosterone (1.0,10.0 and 100.0 nmol/L) significantly re-duced norepinephrine release (P<0.01),and the norepinepherine overflow was similar between the con-trol and 0.1 nmol/L testosterone group (P>0.05).Electrical stimulation of the ventricle evoked norepi-nepherine release,and this was diminished by the perfusion with testosterone at the concentrations of 1.0,10.0 and 100.0 nmol/L (P<0.01).It is suggested that testosterone suppresses ischemia-and electri-cal stimulationinduced norepinepherine release in the isolated rat hearts.
文摘Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10<sup>-5</sup> mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10<sup>-5</sup>～4×10<sup>-5</sup> mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca<sup>2+</sup>-high Mg<sup>2+</sup> ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.
基金supported by grants from Health and Family Planning Commission Foundation of Hubei Province(No.WJ2017M080)the National Natural Science Foundation of China(No.81601507).
文摘Objective The aim of this study was to explore the effect of norepinephrine(NE)on renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis.Methods Atherosclerosis was induced in 21 New Zealand white rabbits by feeding them a cholesterol-rich diet for 16 weeks.Thirteen healthy New Zealand white rabbits were randomly selected as controls.After atherosclerosis induction,standard ultrasonography was performed to confirm that there was no plaque or accelerated flow at the origin of the renal artery.Contrast-enhanced ultrasound(CEUS)was performed at baseline and during intravenous injection of NE.The degree of contrast enhancement of renal cortex and medulla after the injection of contrast agents was quantified by calculating the enhanced intensity.Results The serum nitric oxide(NO)level in atherosclerotic rabbits was higher than that in healthy rabbits(299.6±152 vs.136.5±49.5,P<0.001).The infusion of NE induced a significant increase in the systolic blood pressure(112±14 mmHg vs.84±9 mmHg,P=0.016)and a significant decrease in the enhanced intensity in renal cortex(17.78±2.07 dB vs.21.19±2.03 dB,P<0.001)and renal medulla(14.87±1.82 dB vs.17.14±1.89 dB,P<0.001)during CEUS.However,the enhanced intensity in the cortex and medulla of healthy rabbits after NE infusion showed no significant difference from that at baseline.Conclusion NE may reduce renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis,partly by reducing the serum NO level.
文摘BACKGROUND Bleeding in the gastrointestinal tract is common and transarterial embolization enables the clinician to control gastrointestinal bleeding.Contrast extravasation is a prerequisite for successful embolization.Provocative angiography is helpful in the detection of elusive bleeding.AIM We performed a retrospective analysis of angiographic treatment in patients with lower gastrointestinal hemorrhage and initially negative angiographies,as well as the role of norepinephrine(NE)in unmasking bleeding.METHODS We analyzed 41 patients with lower gastrointestinal bleeding after angiography who had undergone treatment over a period of 10 years.All patients had a positive shock index and needed intensive care.RESULTS In three of four patients,angiography disclosed the site of bleeding when NE was used during the procedure for hemodynamic stabilization.CONCLUSION We suggest that angiography performed after the administration of NE in unstable patients with gastrointestinal bleeding and an initially negative angiography has the potential to unmask bleeding sites for successful embolization.However,this statement must be confirmed in prospective studies.
文摘BACKGROUND: Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotective effects. OBJECTIVE: To observe the effect of 17 beta-estradiol on the content of norepinephrine (NE) and level of tumor necrosis factor (TNF) in submandibular glands of rats with sympathetic nerve injury, and analyze the dose-dependence and pathway of action. DESIGN: A randomized control animal study.SETTINGS: Department of Hand Surgery, the 252 Hospital of Chinese PLA; Department of Hand Surgery, Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: Fifty healthy female Wistar rats were randomly divided into 5 groups with 10 rats in each group: sham-operated group, ovariectomy+6-OHDA+saline group, ovariectomy+6-OHDA+17β-estradiol 50, 200 and 500 μg/kg groups. METHODS: The experiments were carried out in Tongji Medical College, Huazhong University of Science and Technology between October 2005 and March 2006. Bilateral ovaries were only exposed but not resected for the rats in the sham-operated group, but bilateral ovaries were resected in all the other groups. In the ovariectomy+6-OHDA+17β-estradiol 50, 200 and 500 μg/kg groups, the rats were administrated with intraperitoneal injection of 6-OHDA (8 mg/kg), and then immediately given 17β-estradiol of corresponding dosages respectively, once a day for 10 days continuously. Rats in the sham-operated group and ovariectomy+6-OHDA+saline group were administrated with saline of the same volume. After administration, 5 rats in each group were killed to determine the NE contents in bilateral submandibular glands with high performance liquid chromatography-electrochemical detector (HPLC-ECD), and the other 5 rats were used to determine the TNF levels in submandibular glands with enzyme-linked immunosorbant assay.MAIN OUTCOME MEASURES: The NE contents and TNF levels in submandibular glands of rats in each group were observed. RESULTS: All the 50 rats were involved in the analysis of results. ① The NE content was obviously lower in the ovariectomy+6-OHDA+saline group than in the sham-operated group [(1 035±196), (1 823±314) ng/g, P < 0.05], there were no significant differences between the ovariectomy+6-OHDA+17β-estradiol 50 μg/kg group and ovariectomy+6-OHDA+saline group [(1 004±253), (1 035±196) ng/g, P > 0.05], but obviously higher in the ovariectomy+6-OHDA+17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy+6-OHDA+saline group [(1 487±268), (1 939±274), (1 035±196) ng/g, P < 0.05]. ② The TNF level was obviously higher in the ovariectomy+6-OHDA+saline group than in the sham-operated group [(3.498±0.792), (1.893±0.533) ng/g, P < 0.05], there were no significant differences between the ovariectomy+ 6-OHDA+17β-estradiol 50 μg/kg group and ovariectomy+6-OHDA+saline group [(3.328±0.712), (3.498±0.792) ng/g, P > 0.05], but obviously lower in the ovariectomy+6-OHDA+17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy+6-OHDA+saline group [(2.639±0.438), (2.016±0.619), (3.498±0.792) ng/g, P < 0.05]. CONCLUSION: Estrogen has obvious protective effect dose-dependently on 6-OHDA induced chemical sympathetic nerve terminal injury in rats, and it may play its protective role by reducing TNF level and ameliorating inflammatory reaction.
文摘The primary neurotransmitters targeted by currently used antidepressants, such as duloxetine, venlafaxine and fluoxetine, are serotonin and norepinephrine, which also are released in significant amounts in the central nervous system in response to sympathetic nervous system activation. In cultured hippocampal neurons, we have previously shown that norepinephrine induces increased expression of brain-derived neurotrophic factor (BDNF), the PI-3 K/Akt, MAPK pro-survival pathways, the BDNF receptor, TrkB, a transcription factor, and cyclic AMP response element binding protein (CREB). In the present study, we extend these findings of increased BDNF expression to its kinetics of release into the surrounding media. We also evaluate these two cell survival pathways, TrkB and CREB, in response to application of serotonin and/or norepinephrine. Serotonin elicits an earlier, but brief expression and release of BDNF, whereas norepinephrine elicits a more delayed and sustained release of BDNF. In response to both norepinephrine and 5-HT, the presence of BDNF in lysates and subsequent release into the media is significantly increased out to 4 h, as is PI-3 K/Akt activation. Together, these two neurotransmitters increase BDNF expression and release covering the entire 8 h continuum evaluated. The results of this study provide further evidence for a G protein-coupled receptor and a crosstalk-to-TrkB receptor with transactivation signaling across pathways.
文摘Objective: To compare the preventive effect of ephedrine, phenylephrine and norepinephrine on hypotension after lumbar anesthesia in cesarean section and their effects on newborns. Methods: 25 cesarean section women in our hospital from December 2016 to January 2018 were selected and divided into three groups according to different surgical medication, namely, ephedrine group (n=40), phenylephrine group (n=45) and norepinephrine group (n=40). Then the vital signs, neonatal blood gas analysis, neonatal Apgar score, adverse reactions of the three groups were compared. Results: The HR at T0~T3, and SBP and DBP at T0 and T1 had no difference among three groups (P>0.05). The HR, SBP and DBP at T3 ranking in a descending order was norepinephrine group, ephedrine group and phenylephrine group (P<0.05). The PCO2 and PO2 had no difference among three groups (P>0.05). The pH ranking in a descending order was norepinephrine group, ephedrine group and phenylephrine group (P<0.05). The SpO2 ranking in a descending order was phenylephrine group, ephedrine group and norepinephrine group (P<0.05). The Apgar score at birth in ephedrine group and norepinephrine group was significantly lower than that in phenylephrine group (P<0.05), while the Apgar score at post-birth 5 min and 10 min had no difference among three groups (P>0.05). The incidence of hypertension, gastrointestinal reaction, hyperhidrosis and palpitation in the phenylephrine group was significantly lower than that in the norepinephrine group (P<0.05). Conclusion: The phenylephrine and norepinephrine have no difference on the preventive effect of hypotension after spinal anesthesia in cesarean section, while safety of norepinephrine for puerpera and neonates is higher.
基金by Scientific research project plan of Weifang Health Committee(Grant No:wfwsjk2019076).
文摘Objective:To observe the effect of continuous hemofiltration combined with norepinephrine in the treatment of septic shock,and to explore the value of blood purification in the treatment of septic shock.Methods:From November 2018 to December 2020,100 patients with septic shock in the Intensive care unit of our hospital were selected and randomly divided into observation group and control group,with 50 cases in each group.The control group was given conventional treatment,while the observation group was given continuous hemofiltration combined with norepinephrine intervention.The clinical efficacy,Scv02,MAP and oxygenation index(PO_(2)/FiO_(2))of the two groups were compared.The levels of interleukin-6(IL-6),procalcitonin(PCT)and the total number of leukocytes and other inflammatory factors were compared 72 hours after treatment,and the 28-day mortality of the two groups was counted.Results:The total effective rate of the observation group(92.00%)was significantly higher than that of the control group(86.00%),the difference was statistically significant(p<0.05);the 28-day mortality of the two groups was 8.00%in the observation group and 14.00%in the control group,the difference was statistically significant(χ^(2)=4.629,p=0.038);Before treatment,the Scv02,MAP and PO_(2)/FiO_(2)levels of the two groups were significantly higher than those of post-therapy.There was no significant difference between the two groups(p>0.05);After 48 hours of treatment,the levels of Scv02,MAP and PO_(2)/FiO_(2)in the two groups were significantly increased,while the levels of scv02,map,PO_(2)/FiO_(2)in the observation group were more significantly increased than those in the control group(p<0.05);Before treatment,the levels of IL-6,PCT and total white blood cells in the two groups were significantly higher than those of post-therapy(p<0.05)After 72 hours of treatment,the levels of IL-6,PCT and the total number of white blood cells in the two groups decreased significantly,while the levels of IL-6,PCT and the total number of white blood cells in the observation group decreased more significantly than those in the control group(p<0.05).Conclusion:Continuous blood purification combined with norepinephrine can effectively reduce the level of serum inflammatory factors in patients with septic shock,improve hemodynamic indexes,improve survival rate,which is worthy of clinical application.
基金funded by the National Natural Science Foundation of China (Z.P.81560131)Subject Cultivation Project of Zhongnan Hospital of Wuhan University (Bo Hu,No.ZNXKPY2021002)+1 种基金Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (Bo Hu,No.ZNJC202011)Qinghai Province Key R&D and Transformation Projects (S.M.2019-SF-132).
文摘Background The benefits of early use of norepinephrine in endotoxemic shock remain unknown.We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically relevant large animal model.Methods Vasodilatory shock was induced by endotoxin bolus in 30 Bama suckling pigs.Treatment included fluid resuscitation and administration of different doses of norepinephrine,to induce return to baseline mean arterial pressure(MAP).Fluid management,hemodynamic,microcirculation,inflammation,and organ function variables were monitored.All animals were supported for 6 h after endotoxemic shock.Results Infused fluid volume decreased with increasing norepinephrine dose.Return to baseline MAP was achieved more frequently with doses of 0.8µg/kg/min and 1.6µg/kg/min(P<0.01).At the end of the shock resuscitation period,cardiac index was higher in pigs treated with 0.8µg/kg/min norepinephrine(P<0.01),while systemic vascular resistance was higher in those receiving 0.4µg/kg/min(P<0.01).Extravascular lung water level and degree of organ edema were higher in animals administered no or 0.2µg/kg/min norepinephrine(P<0.01),while the percentage of perfused small vessel density(PSVD)was higher in those receiving 0.8µg/kg/min(P<0.05)and serum lactate was higher in the groups administered no and 1.6µg/kg/min norepinephrine(P<0.01).Conclusions The impact of norepinephrine on the macro-and micro-circulation in early-stage endotoxemic shock is dose-dependent,with very low and very high doses resulting in detrimental effects.Only an appropriate norepinephrine dose was associated with improved tissue perfusion and organ function.
基金supported by the Corbett Estate Fund(62285-531021-41800,to EW)the Helen Vosburg McCrillus Plummer and Robert Edward Lee Plummer,Jr.Chair Fund(to JHH).
文摘Neuron-astrocyte interactions are vital for the brain’s connectome.Understanding astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals.Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons.Astrocytes,outnumbering neurons by nearly fivefold,support and regulate neuronal and synaptic function.Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling.This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep,wakefulness,and arousal levels,exploring the involvement of noradrenaline signaling,ion channels,and glutamatergic signaling in different cortical states.These findings highlight the significant impact of astrocytes on large-scale neuronal networks,influencing brain activity and responsiveness.Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation.More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states,requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep-and arousal-related disorders.
文摘Background:In recent years,norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia.Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China.Thus,in this randomized,double-blinded study,we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension.Methods:In a tertiary women’s hospital in Nanjing,China,102 women were allocated with computer derived randomized number to receive prophylactic 8 mg norepinephrine(group N;n=52)or 100 mg phenylephrine(group P;n=50)immediately post-spinal anesthesia,followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80%of the baseline.Our primary outcome was standardized maternal cardiac output(CO)reading from spinal anesthesia until delivery analyzed by a two-step method.Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes.Maternal side effects and neonatal outcomes were collected as well.Results:Compared to group P,women in groupNhad a higherCO(standardizedCO5.8±0.9 vs.5.3±1.0 L/min,t=2.37,P=0.02)and stroke volume(SV,standardized SV 73.6±17.2 vs.60.0±13.3 mL,t=4.52,P<0.001),and a lower total peripheral resistance(875±174 vs.996±182 dyne·s/cm5,t=3.44,P<0.001).Furthermore,the incidence of bradycardia was lower in group N than in group P(2%vs.14%,P=0.023),along with an overall higher standardized heart rate(78.8±11.6 vs.75.0±7.3 beats/min,P=0.049).Other hemodynamics,as well as maternal side effects and neonatal outcomes,were similar in two groups(P>0.05).Conclusions:Compared to equivalent phenylephrine,intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia;however,no obvious maternal or neonatal clinical advantages were observed for norepinephrine.
基金supported by grants from the Beijing Municipal Natural Science Foundation(No.7202157)the Fundamental Research Funds for the Central Universities(No.3332018010)Project of Excellent Talent of Dongcheng District,Beijing(No.2018)。
文摘Background:The peripheral perfusion index(PI),as a real-time bedside indicator of peripheral tissue perfusion,may be useful for determining mean arterial pressure(MAP)after early resuscitation of septic shock patients.The aim of this study was to explore the response of PI to norepinephrine(NE)-induced changes in MAP.Methods:Twenty septic shock patients with pulse-induced contour cardiac output catheter,who had usual MAP under NE infusion after early resuscitation,were enrolled in this prospective,open-label study.Three MAP levels(usual MAP-10 mmHg,usual MAP,and usual MAP+10 mmHg)were obtained by NE titration,and the corresponding global hemodynamic parameters and PI were recorded.The general linear model with repeated measures was used for analysis of variance of related parameters at three MAP levels.Results:With increasing NE infusion,significant changes were found in MAP(F=502.46,P<0.001)and central venous pressure(F=27.45,P<0.001)during NE titration.However,there was not a significant and consistent change in continuous cardiac output(CO)(F=0.41,P=0.720)and PI(F=0.73,P=0.482)at different MAP levels.Of the 20 patients enrolled,seven reached the maximum PI value at usual MAP-10 mmHg,three reached the maximum PI value at usual MAP,and ten reached the maximum PI value at usual MAP+10 mmHg.The change in PI was not significantly correlated with the change in CO(r=0.260,P=0.269)from usual MAP-10 mmHg to usual MAP.There was also no significant correlation between the change in PI and change in CO(r=0.084,P=0.726)from usual MAP to usual MAP+10 mmHg.Conclusions:Differing MAP levels by NE infusion induced diverse PI responses in septic shock patients,and these PI responses may be independent of the change in CO.PI may have potential applications for MAP optimization based on changes in peripheral tissue perfusion.
文摘Tissue concentrations of norepinephrine(NE)are markedly decreased in various regions of the Parkinson’s disease(PD)brain.As in the substantia nigra pars compacta,neuronal dropout and Lewy bodies are prominent changes affecting the locus coeruleus,which is the source of ascending NErgic projections.Despite the major roles of NE throughout the brain,there has been only minimal exploration of pharmacological intervention with NErgic neurotransmission.Cognitive operations,“freezing”of gait,tremor,dyskinesia,REM sleep regulation,and other aspects of brain function are tied into signaling by NE,and there is also evidence that it may have a role in the neurodegenerative process itself.This article reviews the reported pharmacological experience in PD therapeutics.
