Clonidine premedication improves metabolic control in type 2 diabetic patients during ophthalmic surgery

Background. In stressful conditions, increasing blood glucoseconcentrations are closely related to an increase in catecholaminesand cortisol release. Clonidine, a centrally acting     

Effect of alpha 2-adrenergic receptor antagonist (midaglizole) on gastrointestinal motility in conscious dogs

To clarify the physiological role of the mechanism that adrenergic nerve inhibits Ach release from intramural cholinergic nerve endings, the influence of Midaglizole, alpha 2-adrenergic receptor antagonist, to postprandial gastrointestinal motilities in conscious dogs was investigated. Postprandial motilities of gastric antrum, duodenum, ileum, and colon were significantly enhanced by Midaglizole (3.0-5.0 mg/kg body weight, i.v.). These excitatory responses were abolished by atropine (0.05-0.1 mg/kg body weight, i.v.). On the other hand, in most cases (29 cases out of 32), when Midaglizole was administered during quiesent phase of IMC, no change occurred in gastrointestinal motility. However, after subliminal dose of pentagastrin or cisapride, which stimulated Ach release from intramural cholinergic neuron without development of motility, was administered, Midaglizole induced phasic, postprandial motility-like contraction in gastrointestinal tract. Even in the fasted state, when Midaglizole was administered intragastrically, irregular contractions with high amplitude occurred in every regions from gastric antrum to colon. And these excitatory responses were abolished by atropine. Similar reaction was observed also in truncal vagotomized dogs. These results suggest that it is the physiological mechanism that adrenergic nerve presynaptically inhibits Ach release from intramural cholinergic neuron, which is the main mechanism of development of postprandial motility, acting on alpha 2-adrenergic receptor, and has tonic control of postprandial motility.     

Effects of perioperative alpha1 block on haemodynamic control during laparoscopic surgery for phaeochromocytoma

Background. Laparoscopic surgery for phaeochromocytoma can causeexcessive catechol amine release with severe hypertension andsinus tachycardia. I.V. calcium antagonists may be used to preventincreases in blood pressure during phaeochromocytoma resection.We investigated the effects of perioperative     

Reduction of vasopressor requirement by hydrocortisone administration in a patient with cerebral vasospasm

A 67-yr-old female received hypertensive, hypervolaemic treatmentfor cerebral vasospasm after severe subarachnoid haemorrhage.After 3 days of continuous vasopressor infusion and despiteadequate hydration and normal cardiac function, the phenylephrinedose had to be increased to obtain the same systolic blood pressure.This tachyphylaxis to phenylephrine infusion was probably causedby down-regulation of  adrenoceptors, and was reversedby giving i.v. hydrocortisone. Br J Anaesth 2001; 86: 138–41     

Regional and temporal changes in cardiovascular responses to norepinephrine and vasopressin during continuous infusion of lipopolysaccharide in conscious rats

Background. Reduced pressor responsiveness to norepinephrine(NE) in sepsis is well documented but the associated regionalhaemodynamic changes are less well characterized, and thereare varying reports of changes in haemodynamic responses toarginine vasopressin (AVP). We compared changes in regionalhaemodynamic responsiveness to AVP and NE during a 24 h continuousinfusion of lipopolysaccharide (LPS) in conscious rats. Methods. Conscious, male Sprague–Dawley rats were infusedwith saline (0.4 ml h^–1) or LPS (150 µg kg^–1h^–1). Renal, mesenteric, and hindquarter haemodynamicresponses to 3 min infusions of AVP (0.25, 0.625, and 1.25 ngkg^–1 min^–1) or NE (75, 250, and 750 ng kg^–1min^–1) were assessed 2, 6, and 24 h after the onset ofLPS or saline. Results. Two and six hours after the onset of LPS, all haemodynamiceffects of NE were markedly reduced, but by 24 h, there wassome recovery in the vasoconstrictor actions of NE althoughthe pressor and bradycardic effects were still depressed. Twohours after the onset of LPS, the cardiovascular effects ofAVP were depressed but there was some recovery in vascular responsivenessat 6 h. By 24 h, only the mesenteric vasoconstrictor effectof AVP was consistently reduced. Conclusions. During low dose LPS infusion, there are differentialchanges in haemodynamic responsiveness to AVP and NE, whichshow different temporal and regional profiles of recovery withtime. Furthermore, reduced pressor responsiveness to NE is notnecessarily accompanied by a reduced capacity of vessels forvasoconstriction.     

Effects of epidural anaesthesia on intestinal oxygenation in pigs

Background. Perioperative intestinal hypoperfusion is a majorcontributing factor leading to organ dysfunction. It can becaused by stress as a result of surgical manipulation or hypoxia.Additionally, anaesthesia can affect intestinal oxygenation.This animal study was designed to assess the effects of reducedregional sympathetic nervous activity induced by thoracic epiduralanaesthesia on intestinal oxygenation. Methods. After ethical approval, 16 anaesthetized and acutelyinstrumented pigs were randomly assigned to two groups (epiduralanaesthesia alone vs epidural anaesthesia plus volume loading).The epidural anaesthesia aimed for a T5–T12 block. Measurementswere at baseline and after 1 and 2 h. Results. Epidural anaesthesia was associated with a decreasein mean arterial blood pressure and pronounced mesenteric vasodilatation.Mesenteric blood flow did not change. Intestinal oxygen uptake,mucosal tissue oxygen partial pressure and tissue carbon dioxidepartial pressure remained unchanged. Conclusions. Despite marked systemic hypotension, epidural anaesthesiadid not affect intestinal oxygenation. There was no benefitobtained from volume loading. Br J Anaesth 2003; 90: 212–20     

Sympathetic inhibition of reflex activation of bladder motility during filling at a physiological-like rate in urethane anaesthetized rats

The mean volume of saline (infused at a physiological-like rate) required to elicit neurogenic rhythmic contractions of the detrusor muscle (micturition threshold) in urethane anaesthetized rats was reduced by reserpine pretreatment, as well as by chemical (6-hydroxydopamine) or surgical sympathectomy (bilateral section of the hypogastric nerves). Propranolol pretreatment had no significant effect on micturition threshold but increased the intraluminal pressure at which the rhythmic contractions occurred. In spinal rats (T12L1) a flat pressure volume curve was obtained with only a minor phasic contractile activity. Propranolol administration or bilateral section of the hypogastric nerves significantly increased the intraluminal pressure response to saline filling in spinal rats. Topical tetrodotoxin increased the intraluminal pressure response to saline filling in control spinal rats but not following propranolol administration or bilateral section of the hypogastric nerves. These findings provide evidence for a sympathetic inhibition of the reflex activation of the detrusor muscle in response to a physiological-like filling of the urinary bladder.     

Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock

BACKGROUND: We tested the hypothesis that sodium nitroprusside (SNP) might improve the impairment of hepatosplanchnic microcirculatory blood flow (MBF) in septic shock. METHODS: Fourteen pigs were anaesthetized and their lungs mechanically ventilated. Sepsis was induced with i.v. infusion of live Pseudomonas aeruginosa [1x10(8) colony forming units (CFU) ml(-1) kg(-1)] for 1 h. Sixty minutes later, the animals received in a random succession either SNP or normal saline for 30 min. Mean arterial pressure (MAP), cardiac index (CI), mean pulmonary artery pressure (MPAP), carbon dioxide tension of the ileal mucosa (PCO2; by gas tonometry), ileal mucosal and hepatic MBF by laser Doppler flowmetry, blood gases, and lactates were assessed before, during administration, and 30 min after discontinuing the test drug. RESULTS: Bacterial infusion promoted hypodynamic shock (MAP -18%, CI -33%, ileal MBF -19%, and hepatic MBF -27%), which was converted to normodynamic shock by resuscitation. During SNP infusion, ileal mucosal MBF significantly increased (+19%) compared with control (P = 0.033). Although hepatic MBF increased (+42% from baseline), this did not differ from control. In order to maintain a constant central venous pressure and MAP, fluid loading and norepinephrine (P < 0.01) were increased. Acid-base status was not altered by SNP. CONCLUSIONS: In a resuscitated porcine model of the early phase of septic shock, SNP improved ileal mucosal MBF but required a concomitant increase in fluid and norepinephrine supplements to maintain constant systemic haemodynamic parameters.     

Effects of nitric oxide synthase inhibition on dexmedetomidine-induced vasoconstriction in healthy human volunteers

Background: This study aimed to assess the contribution of endothelial nitricoxide synthesis to the net responses of human peripheral bloodvessels in vivo to the selective ₂-adrenoceptor agonist dexmedetomidine. Methods: Two groups of healthy young men were studied. In the first experiment,after brachial plexus block, the responses of digital arteriesto systemically administered dexmedetomidine (target plasmaconcentration 1.2 ng ml^–1) were studied using a photoplethysmograph(n=10) during i.a. infusions of saline and the nitric oxidesynthase (NOS) inhibitor N^G-monomethyl-L-arginine (L-NMMA) (8µmol min^–1). In a separate experiment, after pre-treatmentwith acetylsalicylic acid, responses to increasing doses ofdexmedetomidine (0.01–164 ng min^–1) in the presenceand absence of L-NMMA were compared in dorsal hand veins (DHV)(n=10) using linear variable differential transformers. Results: L-NMMA significantly augmented dexmedetomidine-induced vasoconstrictionof digital arteries as assessed by an increase in light transmissionthrough a finger and by a decrease in finger temperature. Themean (95% confidence interval) extent of the additional effectof L-NMMA over the constrictor effect of dexmedetomidine alonewas 19% (14–24) (P<0.0001). In DHV, L-NMMA had variableeffects on the dexmedetomidine-constriction dose–responsecurve. In three subjects, the curve was shifted significantlyto the left (with a >10-fold difference in ED₅₀), but ED₅₀was only marginally affected by L-NMMA in the other subjects(difference in ED₅₀ <five-fold). Conclusions: The endothelial NOS enzyme has a significant role in opposingthe vasoconstrictor action of dexmedetomidine at drug concentrationswithin the therapeutic range.     

Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions

The     

Pulmonary vasodilator effects of norepinephrine during the development of chronic pulmonary hypertension in neonatal lambs

Background. This experimental study was performed to determinethe effects of norepinephrine on: (i) the pulmonary vasculartone during the development of pulmonary hypertension (PH) inthe fetus and (ii) the circulatory adaptation at birth afterchronic intrauterine PH. Methods. Chronically instrumented fetal lambs were randomizedinto two groups: (i) a group with PH obtained by antenatal partialligation of the ductus arteriosus (DA) (n=9) and (ii) a controlgroup without DA ligation (n=6). Pulmonary vascular responsesto norepinephrine (1.5 µg min^–1) were measured inutero 7 days after surgery. At day 8 post-surgery, after delivery,animals were ventilated for 3 h with oxygen 100%. The groupwith PH was randomly assigned to receive norepinephrine or saline. Results. Mean pulmonary artery pressure (PAP) and pulmonaryvascular resistance (PVR) were higher in the PH group (P<0.01).Norepinephrine-induced decrease in PVR was more pronounced inthe PH group than in the control group (63 vs 35%, respectively;P<0.01). In the PH group, the decrease in PVR during mechanicalventilation was greater in the animals receiving norepinephrinethan in the animal receiving saline (from 1.05 (0.12) to 0.1(0.02) vs from 1.04 (0.1) to 0.2 (0.04) mm Hg ml^–1 min^–1,respectively; P<0.01). After 3 h of ventilation, mean PVRin the PH lambs treated by norepinephrine was similar to thosemeasured in the control lambs. Aortic pressure was higher inthe group treated with norepinephrine. Conclusion. The data suggest that norepinephrine may improvepost-natal pulmonary adaptation in the newborn with persistentPH both by increasing systemic vascular pressure and by increasingpulmonary blood flow.     

Effect of preoperative beta-blockade on perioperative mortality in coronary surgery

Background. Many preoperative factors can influence perioperativemortality in cardiac surgery. Because the perioperative useof ß-blocking agents may reduce perioperative cardiaccomplications in non-cardiac surgery, we considered the possibilitythat ß-blocking agents could improve survival in coronarysurgery patients. Methods. In a retrospective study on 1586 patients undergoingcoronary bypass surgery, the relative risk of 30-day mortalitywas determined in relation to preoperative risk factors andmedication. Factors included patient characteristics, pre-existingillness, specific cardiovascular risk factors, cardiac statusand urgency of surgery. Treatment with ß-blockingagents, calcium antagonists, angiotensin-converting enzyme inhibitors,nitrates, anti-arrhythmic agents, diuretics and antithromboticagents was taken into account. Results. Sex, age, chronic obstructive pulmonary disease, urgencyand the preoperative use of diuretics and chronic ß-blockingtherapy were found to be linked to mortality (P<0.05). Backwardstepwise regression testing identified age, urgency and ß-blockingtherapy as independent factors that could predict mortality. Conclusions. Increasing age and urgency of surgery are associatedwith greater mortality, whereas preoperative ß-blockingtherapy is associated with less mortality. The characteristicsof patients who received chronic ß-blockade did notdiffer significantly from those of patients who did not. Theresults suggest that chronic preoperative ß-blockertherapy reduces 30-day mortality in coronary surgery. Br J Anaesth 2003; 90: 27–31     

Esmolol in the anaesthetic management of a boy with Romano–Ward syndrome

The Romano–Ward syndrome is a congenital form of long Q-T syndrome which frequently causes syncope, dysrhythmias and sudden death. Certain anaesthetic drugs can precipitate dangerous dysrhythmias. Chronic β-adrenergic blockade is the therapy of choice for symptomatic patients and establishment of complete and total β-blockade is recommended for symptomatic patients having anaesthesia and surgery. We report the successful use of esmolol to establish rapid and total β-blockade before a short elective out-patient procedure and suggest that esmolol may be useful for other patients with Romano–Ward syndrome having anaesthesia and surgery.     

The effects of clonidine on ropivacaine 0.75% in axillary perivascular brachial plexus block

INTRODUCTION: The new long-acting local anesthetic ropivacaine is a chemical congener of bupivacaine and mepivacaine. The admixture of clonidine to local anesthetics in peripheral nerve block has been reported to result in a prolonged block. The aim of the present study was to evaluate the effects of clonidine added to ropivacaine on onset, duration and quality of brachial plexus block. METHODS: Patients were randomly allocated into two groups. In group I brachial plexus was performed using 40 ml of ropivacaine 0.75% plus 1 ml of NaCL 0.9%, and in group II brachial plexus was performed using 40 ml of ropivacaine 0.75% plus 1 ml (0.150 mg) of clonidine. Onset of sensory and motor block of radial, ulnar, median and musculocutaneous nerve were recorded. Motor block was evaluated by quantification of muscle force, according to a rating scale from 6 (normal contraction force) to 0 (complete paralysis). Sensory block was evaluated by testing response to a pinprick in the associated innervation areas. Finally, the duration of the sensory block was registered. Data were expressed in mean+/-SD. For statistical analysis a Student t-test was used. A P-value of < or = 0.05 was considered as statistically significant. RESULTS: The duration of blockade was without significant difference between the groups. Group I: 718+/-90 min; Group II: 727+/-117 min. There was no intergroup difference in sensory and motor onset or in quality of blockade. CONCLUSION: The addition of clonidine to ropivacaine 0.75% does not lead to any advantage of block of the brachial plexus when compared with pure ropivacaine 0.75%.     

N受体α4β2亚型在异氟醚抑制大鼠海马突触长时程增强中的作用

目的 评价海马神经元N受体α4β2亚型在异氟醚抑制大鼠海马突触长时程增强(LTP)中的作用.方法 健康成年雄性SD大鼠,取海马组织,制备海马脑片.取70张脑片,随机分为10组(n=7):各组用正常人工脑脊液(aCSF)灌流海马脑片,记录稳定正常的细胞外群峰电位(PS)30 min,LTP组继续给予正常的aCSF灌流,其余各组分别用含异氟醚0.125 mmol/L(I1组)、0.25 mmol/L(I2组)、0.5 mmol/L(I3组)、地棘蛙素0.1 mmol/L(E1组)、1.0 μmol/L(E2组)、地棘蛙素0.1 μmol/L+异氟醚0.25 mmol/L(E1+I2组)、地棘蛙素1.0 μmol/L+异氟醚0.25 mmol/L(E2+I2组)、双氢β-刺酮碱(DHβE)0.1μmol/L(D组)、DHβE0.1μmol/L+异氟醚0.125 mmol/L(D+I1组)的aCSF灌流.采用细胞外微电极记录技术,记录海马脑片CA1区细胞外PS 30 min后,施以高频强直刺激(HFS)15 min,诱发LTP,记录各组HFS结束后5、10、15、20、25、30、40、50、60 min时的PS幅值.结果 与LTP组比较,I1.2.3组、D组、D+I1组、E1+I2组HFS后PS幅值降低,E1.2组HFS后PS幅值升高(P＜0.05),E2+I2组HFS后PS幅值差异无统计学意义(P＞0.05).与I1组比较,D+I1组HFS后PS幅值降低(P＜0.05).与I2组比较,E1+I2组、E2+I2组HFS后PS幅值升高(P＜0.01).结论 异氟醚通过拮抗海马神经元N受体α4β2亚型从而抑制了突触LTP的形成.     

5氮2脱氧胞苷与三苯氧胺协同抗雌激素受体α阴性乳腺癌的体外实验研究

目的观察5氮2脱氧胞苷（5-aza—CdR）对雌激素受体α（ERα）阴性人类乳腺癌细胞株MDA—MB-231和MDA—MB-435ERα基因诱导表达作用;5-aza—CdR联合三苯氧胺（TAM）对ERα阴性乳腺癌细胞的体外抑制作用。方法应用甲基化特异性PCR（MSP）检测MDA—MB-231和MDA—MB-435细胞和20例ERα阴性乳腺癌组织ERα基因核心启动子区CpG岛甲基化情况;5-aza—CdR处理MDA—MB-231和MDA—MB-435细胞,逆转录PCR（RT—PCR）检测ERαmRNA表达;5-aza—CdR、TAM分别或联合作用于MDA—MB-231和MDA—MB-435细胞,M1T比色法分析细胞生长抑制作用,流式细胞仪测定细胞周期分布和凋亡率。结果适当浓度的5-aza—CdR能诱导MDA—MB-231和MDA—MB一435细胞表达ERctmRNA,抑制细胞生长、阻滞细胞周期于G0／G1期,诱导细胞凋亡;TAM对MDA—MB-231和MDA—MB-435细胞生长、细胞周期无影响;而两药联合时能显著抑制细胞生长,诱导细胞凋亡,凋亡率分别为48、8％和53、1％。结论5-aza—CdR能诱导ERα阴性乳腺癌表达ERctmRNA,恢复ERα阴性乳腺癌细胞对TAM的敏感性,联合TAM能协同抑制ERα阴性乳腺癌细胞生长,诱导细胞凋亡,从而为ERα阴性乳腺癌开辟新的内分泌治疗途径提供实验依据。