Potentiation of 5-hydroxytryptamine (5-HT) responses by a 5-HT uptake inhibitor in pulmonary and systemic vessels: effects of exposing rats to hypoxia

The aim was to determine whether uptake of 5-hydroxytryptamine (5-HT) by the 5-HT transporter (SERT) modulates contractile responses to 5-HT in rat pulmonary arteries and whether this modulation is altered by exposure of rats to chronic hypoxia (10% oxygen; 8 h/day; 5 days). The effects of the SERT inhibitor, citalopram (100 nM), on contractions to 5-HT were determined in isolated ring preparations of pulmonary artery (intralobar and main) and compared with data obtained in systemic arteries. In intralobar pulmonary arteries citalopram produced a potentiation (viz. an increase in potency, pEC₅₀) of 5-HT. The potentiation was endothelium-dependent in preparations from normoxic rats but endothelium-independent in preparations from hypoxic rats. In main pulmonary artery endothelium-independent potentiation was seen in preparations from hypoxic rats but no potentiation occurred in preparations from normoxic rats. In systemic arteries, citalopram caused endothelium-independent potentiation in aorta but no potentiation in mesenteric arteries; there were no differences between hypoxic and normoxic rats. It is concluded that SERT can influence the concentration of 5-HT in the vicinity of the vasoconstrictor receptors in pulmonary arteries. The data suggest that in pulmonary arteries from hypoxic rats, unlike normoxic rats, the SERT responsible for this effect is not in the endothelium and, hence, is probably in the smooth muscle. The data are compatible with reports that, in the pulmonary circulation, hypoxia induces/up-regulates SERT, and hence increases 5-HT uptake, in vascular smooth muscle. The findings may have implications in relation to the suggested use of SERT inhibitors in the treatment of pulmonary hypertension.     

Effects of bufotenine and p-chlorophenylalanine on stress induced behaviour

Two experiments were conducted in which it was found that bufotenine attenuated, relative to controls: (1) the manifestation of frustrative behaviour as a function of non-reward in a double runway situation and (2) fear reactions typically observed in an open field test. In both experiments, p-chlorophenylalanine, a serotonin depletor, was used effectively to counteract the behavioural effects of bufotenine. The results were interpreted as being in agreement with the general hypothesis that bufotenine reduces an animal's responsiveness to stimulus events. It was also suggested that the behavioural effects of bufotenine are related to its influence on normal serotonin metabolism.This research was supported by a National Research Council grant (# APA-287) awarded to the first author and by the Public Health Service, Government of Saskatchewan.     

Drug antagonism and reversibility of the binding of indoleamines in brain.

The specificity of the binding of serotonin to brain preparations was investigated with various competitive agents. A probable relationship between their structure and their capability of displacement was suggested. Bufotenine and morphine displaced serotonin (0.5 × 10^?5 M) binding to synaptic membranes 87 and 49% respectively. Dissociation constants of the binding of 5-HT and tryptamine to synaptic membranes, and displacement constants of certain drugs were determined. The binding of 5-HT and tryptamine to calf brain preparations was also investigated by equilibrium dialysis, in order to determine affinity constants and reversibility of the binding. Differences were noted in the specificity of binding sites for serotonin and tryptamine, suggesting a different binding site for tryptamine. Extrapolations of Scatchard plots were used for determination of the constants. A characteristic low dissociation constant was found for 5-HT in synaptic membranes (K ～ 1 × 10^?6 M). Probably, the binding macromolecule (receptor?) is a proteolipid.     

The effects of glucagon on the pulmonary circulation in the dog

The effects of an i.v. infusion of glucagon, 5 μg/kg/min, on the pulmonary and systematic circulation were studied in open chest dogs. Glucagon enhanced pulmonary blood flow, pulmonary artery blood pressure reduced left arterial pressure. Pulmonary pressure gradient rose, calculated pulmonary vascular resistance remained unaltered. Systematic blood pressure fell insignificantly, peripheral vascular resistance declined. In conclusion glucagon actively dilates the peripheral vascular bed and exerts no effect on the pulmonary vascular caliber.     

氟伐他汀对肺动脉高压大鼠5-羟色胺转载体表达的影响

目的观察氟伐他汀对野百合碱(MCT)所致的肺动脉高压大鼠肺组织5-羟色胺转载体(5-HTT)表达的影响。方法62只大鼠随机分为3组:①M+F组:大鼠首先给予MCT(40 mg/kg)皮下注射和氟伐他汀(1 mg/kg)灌胃,每日各1次,连续2周。第3~6周继续按氟伐他汀初始给药方案灌胃,不再进行MCT皮下注射。②MCT组:实验前2周给予MCT(40 mg/kg)1次/d皮下注射,第3~6周末给予同氟伐他汀等体积的0.9%盐水灌胃;③Saline组:分别于实验前2周及第3~6周给予等体积的盐水皮下注射和灌胃。分别于不同时间点,对大鼠的血流动力学及相关参数和5-HTT的表达情况进行测定。结果MCT组大鼠于实验第2周末即出现显著的肺动脉高压伴5-HTT蛋白水平异常增高,且在观察期间逐渐增高。M+F组大鼠第6周末出现肺动脉压异常增高,但未伴5-HTT表达增高。结论氟伐他汀能有效抑制5-HTT表达上调,该作用可能与其对大鼠肺动脉高压的抑制作用有关。     

The effect of epinephrine following practolol on the pulmonary circulation of dogs

Epinephrine (1 and 2 μg/kg/min) was infused in 10 urethane-anesthetized dogs following administration of practolol. Practolo. was administered to block the cardiac β-adrenoceptors and thereby permit a better assessment of the direct action of epinephrine on the pulmonary circulation.Following practolol, both infusion rates of epinephrine were associated with an increase in cardiac output, stroke volume, mean pulmonary arterial and venous pressures and no change in heart rate and pulmonary blood volume. It is concluded that epinephrine, in the doses used, produces a mild increase in ‘tone’ of the pulmonary arterial and venouse system.     

Effect of APMO on pulmonary and arterial blood pressure; a comparison with aminorex

The effect of APMO on arterial and pulmonary blood pressure was studied in dogs. When compared on mg/kg basis, the arterial and pulmonary pressor effects of APMO and the ratio (Δ pul. BP)/(Δ art. BP) were less than those of d-amphetamine and aminorex. Tachyphylaxis developed to the pressor effects fo APMO and d-amphetamine on both arterial and pulmonary systems. In the case of aminorex, tachyphylaxis developed to its pressor effect on the arterial but not on the pulmonary system.     

Concerning the nature of the histamine-antagonistic effect of adrenaline in the pulmonary circulation

Summary In guinea pig heart-lung-preparations histamine provoked an increase of the pulmonary vascular resistance with corresponding increase of the pulmonary artery pressure.Administration of adrenaline prior to histamine prevented the histamine effect completely. Isoproterenol acted like adrenaline, noradrenaline was ineffective.Adrenaline by its own had no relaxing effect on the pulmonary vessels but even increased the vascular resistance. In contrast, isoproterenol decreased the vascular resistance.The -blocking agent propranolol prevented the histamine-antagonistic adrenaline and isoproterenol effect, and increased the histamine effect on the pulmonary vessels. The -blocking drug dibenamine did not inhibit the antispastic effect of adrenaline nor the spastic effect of histamine.The increase of the pulmonary vascular resistance provoked by adrenaline was enhanced by propranolol and abolished by dibenamine. The decrease of the resistance provoked by isoproterenol was blocked by propranolol.According to these observations, adrenaline antagonizes the spastic histamine effect on the pulmonary vessels by a mechanism involving stimulation of -adrenergic receptors. The concurrent increasing effect of adrenaline on the vascular resistance is presumably due to -adrenergic stimulation.     

头低位卧床对肺血流影响的试验研究

目的观察-6°头低位卧床(HDT-6°)对肺循环血流的影响,并探讨其与肺弥散功能的关系。方法采用YK-10循环系统监测仪和HP2500超声诊断仪,对16名健康男性受试者90minHDT-6°卧床及21dHDT-6°卧床前、后及卧床不同时间肺循环血流、肺血容量、右心输出量等有关指标分别进行了测试。结果在90min卧床试验中,HDT-6°卧床肺血容量较卧床前坐位显著增加,随卧床时间延长,肺血容量渐减少,90min左右已显著少于平卧位水平。在21d卧床中,第3天最低,第7天测量仍显著低于卧床前平卧位对照值,以后保持相对稳定。起床后第3天平卧位测量仍低于卧床前。右心输出量在卧床第3天即显著下降,之后保持相对稳定,在起床第3天测量基本恢复;每搏量在卧床第7天显著降低,一直持续到起床第3天,而在这个阶段,心率则逐渐增加,卧床第20天和起床第1、3天均比卧床前有显著增加。结论头低位卧床使肺血流量增加的同时,增加了肺循环的灌注压,有肺间质水肿的潜在危害。同时肺动脉压升高,以及机体通过神经体液的自我调节,反过来减少了肺灌注,肺毛细血管血量的减少,有自我保护的作用。     

氟西汀对大鼠肺动脉平滑肌细胞体外增殖的影响

目的观察氟西汀对大鼠肺动脉平滑肌细胞体外增殖的影响并探讨其可能的机制。方法采用肺动脉平滑肌细胞(PASMC)体外培养的方法,观察氟西汀对PASMC增殖及细胞周期的影响。实验细胞分为4组:①正常对照组(Control):培养液含10%胎牛血清的高糖DMEM;②5-HT组:培养液含10%胎牛血清的高糖DMEM,其中加入终浓度为5μg/mL的5-HT的培养液100μL;③Flu组:培养液含10%胎牛血清的高糖DMEM,其中加入终浓度为10μg/mL的Flu的培养液100μL;④5-HT+Flu组:培养液含10%胎牛血清的高糖DMEM,其中加入培养液100μL(其中5-HT终浓度为5μg/mL,Flu终浓度为10μg/mL)。4组细胞均在常规条件下培养,分别于实验第24、48及72小时采用MTT法测定各组细胞的吸光度值(A490),并采用流式细胞周期分析方法测定各组细胞不同时间点细胞周期分布的特点。结果 PASMC离体干预实验结果表明,5-HT+Flu组细胞随着氟西汀浓度增高或时间延长,A490较对照组逐渐降低。细胞周期分析显示,氟西汀作用于PASMC 72 h后,细胞周期分布表现为S期细胞比例下降,G0/G1期细胞比例上升。结论氟西汀可有效拮抗5-HT刺激所致的PASMC增殖,且这一作用可能与氟西汀阻碍PASMC向DNA合成期转化有关。     

Differentiaton of neuropharmacological actions of apomorphine and d-amphetamine.

The dopaminergic agonists apomorphine and d-amphetamine elicit hyperthermic, hyperkinetic and stereotypic responses in the rabbit. The present investigation compares the influence exerted by various serotonergic antagonists upon these activities. Apomorphine-induced hyperthemia was antagonized by p-chlorophenylalanine (pCPA), cyproheptadine and cinanserin and was restored in pCPA-pretreated rabbits by regeneration of central serotonin levels, d-Amphetamine-induced hyperthermia was reduced by pCPA; restored in pCPA-pretreated animals by regeneration of central serotonin levels; and was uninfluenced by cyproheptadine and cinanserin. Apomorphine-induced locomotor stimulation was unaltered by serotonergic antagonists; however, these same doses of anti-serotonergic agents all markedly reduced d-amphetamine-induced hyperkinesia. Serotonergic antgaonists also failed to affect apomorphine-induced compulsive gnawing but did significantly enhance d-amphetamine-induced compulsive gnawing. It is concluded from these data that the neuropharmacological activities of apopmorphine and d-amphetamine in the rabbit differ in their dependence upon central serotonergic mechanisms.     

Blood pressure responses to local application of serotonergic agents in the nucleus tractus solitarii

The effects of serotonin applied directly to the region of the medulla oblongata which contains the nucleus tractus solitarii, nucleus intercalatus, nucleus originis dorsalis vagi and the nucleus origins nervi hypoglossi were investigated in anesthetized rats. A dose dependent increase in blood pressure with variable changes in heart rate was observed after unilateral application of serotonin into the nucleus tractus solitarius. The serotonergic antagonists, 2-bromolysergic acid diethylamide (locally applied) and metergoline (systemically administered) significantly attenuated the serotonin-induced pressor response. Fluoxetine, a serotonin uptake inhibitor, significantly enhanced the magnitude of the pressor response, but did not prolong it. The present data suggest that enhancement of serotonergic activity in the region of the nucleus tractus solitarius produces a neurogenic pressor response.     

Interaction of d-amphetamine with pentobarbital and chlordiazepoxide: Effects on punished and unpunished behavior of pigeons

Key pecking of two pigeons was maintained under a multiple schedule of food presentation. In the presence of one keylight stimulus responding produced food according to a fixed-interval 5-min schedule. Additionally, during this component, each 50th response produced electric shock. When a different keylight stimulus was present, key pecking resulted in food delivery under a variable-interval 3-min schedule. Responding was suppressed by schock presentation (punishment) but was still positively accelerated throughout each fixed-interval cycle; steady response rates occurred during the alternate component when only the variable-interval schedule was in effect. Overall rates of punished responding were largely unchanged with d-amphetamine (0.1–3.0 mg/kg); unpunished responding was generally either increased slightly or was decreased. Pentobarbital and chlordiazepoxide (1.0–17.0 mg/kg) administered alone increased both punished and unpunished responding at most doses. Combinations of d-amphetamine with either pentobarbital or chlordiazepoxide produced increases in punished responding that exceed those obtained with either of these drugs alone. The combined effects of d-amphetamine and either pentobarbital or chlordiazepoxide on unpunished responding depended on the individual dose combinations. Combinations of d-amphetamine with pentobarbital or chlordiazepoxide produced effects on both punished and unpunished responding that differed substantially from those obtained when any of these drugs were administered separately.     

异氟醚对老年人肺换气功能的影响

目的 探讨临床常用浓度的异氟醚同异丙酚-芬太尼相比是否可抑制老年人的低氧性肺血管收缩(HPV),降低肺换气功能。方法 随机选择仰卧位非开胸手术的全麻老年病人20例。先行异丙酚-芬太尼静脉麻醉,20分钟后抽取动脉血和混合静脉血做血气分析,然后改用异氟醚吸入麻醉,分别在最低肺泡有效浓度(MAC)达到1.0和1.5,并维持20分钟后采取动脉血和混合静脉血做血气分析。术中行有创血压及中心静脉压监测,以维持血流动力学的平稳。结果P(A-a)O_2及PaO_2虽有下降但无显著性差异。Qs/Qt及乳酸(LAC)无明显增高。结论 1.5MAC以下的异氟醚对HPV无明显的抑制作用。在保证血流动力学平稳的情况下,此浓度的异氟醚可用于心肺功能正常的老年人。     

抗结核药物对肺结核合并乙型肝炎病毒感染患者肝功能的影响

目的：探讨抗结核药物对肺结核合并乙型肝炎病毒（ HBV）感染患者肝功能的影响。方法选取2011年3月—2014年3月水矿集团总医院收治的肺结核患者147例,其中乙型肝炎病毒标记物（ HBV-M）阳性患者62例作为观察组,HBV-M阴性患者85例作为对照组。两组患者均予以相同的抗结核治疗方案。观察两组患者肝功能指标、肝功能损害情况、肝功能损害出现及恢复时间。结果观察组患者血清丙氨酸氨基转移酶（ ALT）水平及血清总胆红素（ TBL）水平高于对照组,肝功能损害发生率高于对照组,肝功能损害出现时间早于对照组,肝功能恢复时间长于对照组,差异均有统计学意义（ P<0.05）。结论抗结核药物对肺结核合并HBV感染患者肝功能损害明显,故应制定合理的治疗方案,加强对患者病情的监测,根据患者自身情况合理用药,降低肝功能损害发生率。     

Endothelial cell dysfunction and cross talk between endothelium and smooth muscle cells in pulmonary arterial hypertension

The pathogenesis of pulmonary arterial hypertension (PAH) involves a complex and multifactorial process in which endothelial cell dysfunction appears to play an integral role in mediating the structural changes in the pulmonary vasculature. Disordered endothelial cell proliferation along with concurrent neoangiogenesis, when exuberant, results in the formation of glomeruloid structures known as the plexiform lesions, which are common pathological features of the pulmonary vessels of patients with PAH. In addition, an altered production of various endothelial vasoactive mediators, such as nitric oxide, prostacyclin, endothelin-1, serotonin, chemokines and thromboxane, has been increasingly recognized in patients with PAH. Because most of these mediators affect the growth of the smooth muscle cells, an alteration in their production may facilitate the development of pulmonary vascular hypertrophy and structural remodeling characteristic of PAH. It is conceivable that the beneficial effects of many of the treatments currently available for PAH, such as the use of prostacyclin, nitric oxide, and endothelin receptor antagonists, result at least in part from restoring the balance between these mediators. A greater understanding of the role of the endothelium in PAH will presumably facilitate the evolution of newer, targeted therapies.     

Interaction of nitric oxide and renin angiotensin system in pulmonary arterial circulation of RHR

We investigated the interaction between nitric oxide and the renin angiotensin system in regulating isolated pulmonary arterial tension and pulmonary arterial pressure (PAP) in renal hypertensive rats (RHR) made by complete ligation of left renal artery. Losartan induced a depressor response that was smaller in RHR than in normotensive rats (NR) (3.3 and 7.0 mmHg, respectively, at 3.0 mg/kg, p<0.05), and the response was significantly reduced by N(G)-nitro-L-arginine methyl ester (L-NAME). Angiotensin II elevated the PAP (7.6 and 10.8 mmHg at 0.1 mug/kg; 20.3 and 23.6 mmHg at 1.0 mug/kg, respectively) and contracted the isolated pulmonary artery (pD(2): 8.79 and 8.71, respectively) from both NR and RHR with similar magnitude, and these effects were significantly enhanced by L-NAME in NR, but not in HRR. Acetylcholine lowered the PAP slightly less effectively in RHR than in NR (3.8 and 6.0 mmHg at 10 mug/kg, respectively) and relaxed the pulmonary artery precontracted with norepinephrine in both rats with similar magnitude (E(max): 60.8 and 63.6%, respectively), and the effect being completely abolished after pretreatment with L-NAME or removal of endothelial cells. These results suggest that nitric oxide interacts with renin angiotensin system to control the pulmonary vascular tension and pulmonary arterial circulation of RHR.     

201例肺部感染住院患者抗菌药物应用分析

目的:了解我院肺部感染住院患者抗菌药物临床应用情况,并分析其合理性.方法:抽取我院2010年1月1日-2011年12月31日出院的20,份肺部感染患者病历,统计患者概况、病原学检查及抗菌药物使用情况,对抗菌药物的使用频率、药物利用指数及用药合理性进行分析.结果:201例患者所应用的抗菌药物涉及7类23种,头孢菌素类和喹诺酮类使用频率最 高;抗茵药物均为静脉给药,联合用药率为77.61%,以二联用药为主;病原学检查送检率58.7.%,阳性率36.44%.结论:我院肺部感染住院患者应用抗菌药物存在的不合理问题主要是老年患者用药剂量偏大,给药频次不规范,不合理的联合用药.     

慢性阻塞性肺疾病肺动脉高压与气流受限的相关性研究

目的探讨慢性阻塞性肺疾病（COPD）相关性肺动脉高压的发生率、及其与气流受限的相关性。方法对82例稳定期的COPD患者及26例健康对照者进行静态肺功能、血气分析及超声心动图检测。COPD患者依据肺功能指标进一步分级;根据超声心动图检测的肺动脉收缩压（PSAP）值,将COPD患者分为COPD并肺动脉高压组（PASP≥40mmHg）和单纯COPD组（PASP〈40mmHg）。结果 COPD患者肺动脉高压的发生率为22%,进一步分层发现轻,中、重、极重度COPD患者肺动脉高压发生率分别为5%、27%、29%和54%（χ2=9.04,P〈0.05）,两两比较仅极重度COPD组与轻度COPD组肺动脉高压发生率有显著性差异,其他组间比较差异无统计学意义。COPD并肺动脉高压组及单纯COPD组第一秒用力呼气容积占预计值的百分比（FEV1占预计值%）、FEV11/用力肺活量（FVC）（FEV1/FVC）、动脉血氧分压（PaO）2均较健康对照组降低（P〈0.01）。COPD并肺动脉高压组与单纯COPD组比较FEV1占预计值%、FEV1/FVC、一氧化碳弥散量占预计值的百分比（DLCO占预计值%）、动脉血二氧化碳分压（PaCO）2差异均无统计学意义（P均〉0.05）;两组间PaO2比较差异有统计学意义（P〈0.01）。COPD并肺动脉高压组、单纯COPD组及健康对照组3组间年龄及性别相比差异均无统计学意义（P均〉0.05）。PASP与FEV1占预计值%、FEV1/FVC、DLCO占预计值%呈显著负相关（分别为：r=-0.42,r=-0.52,r=-0.38,均P〈0.01）,PASP与PaO2相关性更强（r=-0.61,P〈0.01）。结论随着COPD病情的加重,肺动脉高压的发生率随之增加。气流受限在肺动脉高压的形成中并非单一因素,部分COPD患者存在与气流受限＂不成比例＂的肺动脉高压。     

肺栓塞的影像学诊断方法及研究进展

肺栓塞是临床常见的急性心肺血管疾病，是心血管疾病最常见的死亡原因之一。近年来，尽管肺栓塞的各种诊断技术迅速发展，但仍有一部分肺栓塞患者被误诊或漏诊。目前诊断肺栓塞最准确、最有价值的手段为影像学检查，本文旨在对临床常用的肺栓塞影像学诊断方法及其最新研究进展作总结，从而为肺栓塞的准确诊断提供更全面、可靠的临床思路。