Nitric oxide administration after the ventilator: evaluation of mixing conditions

Background: Because of the potential toxicity of nitric oxide (NO) and its oxidising product nitrogen dioxide (NO₂), any system for the delivery of inhaled NO must aim at stable and predictable levels of NO and as low concentrations as possible of NO₂.
Methods: In a laboratory set-up, we have evaluated mixing conditions in a system where NO is added after the ventilator with continuous flow. Mixing was studied by using carbon dioxide (CO₂) as a tracer gas since capnography has a short response time (360 ms) in comparison with measurements of NO with electrochemical fuel cells (response time of 18s). CO₂ (in volumes corresponding to an ideal mixture of 1,3 and 6%) was fed, after the ventilator, either into plain breathing tubing, into one or two soda lime absorbers, or into an empty and a soda lime-filled canister, at different ventilatory rates and different I: E ratios. Samples were drawn from the inspiratory limb close to the Y-piece. NO was added in the same way and in the same volume as the highest concentration of CO₂.
Results: CO₂ added to plain tubing resulted in peak levels up to five times the set levels, while addition to a mixing box with an empty and a soda lime-filled canister resulted in even mixing with gas concentrations close to the ideal. When NO was fed into plain tubing, low levels were measured at the Y-piece, indicating poor mixing. Gas supply to a mixing chamber resulted in even concentrations.
Conclusions: Even and predictable levels of NO can be obtained with continuous flow of NO to the inspiratory limb, after the ventilator, if a mixing chamber is used. To obtain adequate mixing, the volume of the mixing box should be greater than the tidal volume.     

Association analysis of CA repeat polymorphism of the endothelial nitric oxide synthase gene with essential hypertension in Japanese

The nitric oxide synthase (NOS) gene is thought to be associated with essential hypertension (EH), because NO is implicated in endothelium-mediated vasodilation. We investigated the possible association between the alleles of simple tandem repeat DNA polymorphism of the endothelial constitutive NOS (cNOS) gene and EH in Japanese subjects. In all, 100 patients with EH and 123 subjects with normal blood pressure were studied. Polymerase chain reaction was used to amplify the CA repeat site in the endothelial cNOS gene and alleles based on the CA repeat number were determined. The allele frequencies in the hypertensive group and normotensive group were then compared. Twenty-three alleles were identified in this study of Japanese subjects. The overall distributions of allele frequencies in the two groups were not significantly different. However, comparing the allele frequencies in the EH group without left ventricular hypertrophy (LVH) and the normotensive group, the overall distributions were significantly different (p = 0.019). The 33-repeat allele was found more frequently in the EH group without LVH than in the normotensive group (p = 0.000047, Odds ratio = 3.71). In conclusion, the 33-repeat allele of the endothelial cNOS gene is associated with EH without LVH, and may be a genetic marker of EH in Japanese subjects.     

Increased carbon monoxide levels in the nasal airways of subjects with a history of seasonal allergic rhinitis and in patients with upper respiratory tract infection

BACKGROUND: Carbon monoxide (CO) has emerged as an endogenously produced gaseous mediator known to be involved in bronchial smooth muscle regulation. Increased amounts of CO have been found in exhaled air during asthma and lower airway inflammation. Recently CO has been shown to be produced in the nasal airways, but there are no reports of altered CO levels in nasal airways during inflammation. OBJECTIVE: This study was designed to investigate if CO levels increase in the human nasal airways during inflammatory conditions, such as allergy and upper airway respiratory tract infection (URTI). METHODS: CO was sampled separately from the upper and lower airways of 13 healthy control subjects, six patients with a history of allergic rhinitis and six patients with URTI. RESULTS: Nasal CO levels were increased in subjects with allergic rhinitis, compared to healthy controls (2.07 +/- 0.15 ppm, n = 6 and 1.62 +/- 0.08 ppm, n = 13, respectively, P < 0.01). CO levels were also increased in patients with URTI, compared to the same controls (1.92 +/- 0.09 ppm, n = 6, P < 0.05). Normal levels of CO were found in air from the lower airways among subjects with allergic rhinitis, whereas corresponding levels in the URTI patients were increased. CONCLUSION: The present data demonstrates that upper airway CO levels increase in parallel with different inflammatory stimuli, such as allergy and infection, suggesting a role for CO as marker or mediator of nasal inflammation.     

3,6-(二甲氨基)-二苯骈碘杂六环葡萄糖酸盐对AGEP引起的大鼠主动脉平滑肌细胞增殖及牛主动脉内皮细胞内皮素和一氧化氮改变的影响

目的 :观察 3 ,6 (二甲氨基 ) 二苯骈碘杂六环葡萄糖酸盐对AGEP引起的大鼠主动脉平滑肌细胞增殖及牛主动脉内皮细胞内皮素和一氧化氮改变的影响。方法 :采用牛血清白蛋白 (BSA)与不同浓度葡萄糖 (0 ,2 0 ,5 0 ,80mmol·L-1)体外孵育制备糖基化终产物 (AGEP) ,应用 [3 H] TdR掺入法和MTT比色法观察I-93对重度糖化的AGEP诱导的大鼠主动脉平滑肌细胞 (ASMC)增殖的影响 ;应用放射免疫技术及Greiss法观察I -93对AGEP引起的牛主动脉内皮细胞 (BAEC)释放内皮素 1(ET 1)和一氧化氮 (NO)的影响。结果 :I-93 10 -7～ 10 -5mol·L-1能明显抑制AGEP引起的ASMC增殖 ,其 [3 H] TdR掺入量和MTT比色法的最大抑制率分别为79 .4%和 44 .2 %。随AGEP糖浓度的增加 (2 0～ 80mmol·L-1) ,BAEC培养液中ET 1含量亦逐渐上升 [(4 93± 63 )～ (779± 10 5 )ng·L-1] ,I -93 10 -7～ 10 -5mol·L-1能明显抑制重度糖化的AGEP促进ET 1释放的作用 ;I -93对AGEP灭活NO的作用有剂量依赖性抑制效应。结论 :I -93有抑制ASMC增殖的作用 ;对AGEP诱导的BAEC释放ET 1和NO间平衡失调有调节作用 ,在防治阻塞性血管疾病方面I -93具有潜在的应用价值     

Pathophysiology of idiopathic dystonia: findings from genetic animal models

Dystonia is a common movement disorder which is thought to represent a disease of the basal ganglia. However, the pathogenesis of the idiopathic dystonias, i.e. the neuroanatomic and neurochemical basis, is still a mystery. Research in dystonia is complicated by the existence of various phenotypic and genotypic subtypes of idiopathic dystonia, probably related to heterogeneous dysfunctions.In neurological diseases in which no obvious neuronal degeneration can be found, such as in idiopathic dystonia, the identification of a primary defect is difficult, because of the large number of chemically distinct, but functionally interrelated, neurotransmitter systems in the brain.The variable response to pharmacological agents in patients with idiopathic dystonia supports the notion that the underlying biochemical dysfunctions vary in the subtypes of idiopathic dystonia. Hence, in basic research it is important to clearly define the involved type of dystonia.Animal models of dystonias were described as limited. However, over the last years, there has been considerable progress in the evaluation of animal models for different types of dystonia.Apart from animal models of symptomatic dystonia, genetic animal models with inherited dystonia which occurs in the absence of pathomorphological alterations in brain and spinal cord are described.This review will focus mainly on genetic animal models of different idiopathic dystonias and pathophysiological findings. In particular, in the case of the mutant dystonic (dt) rat, a model of generalized dystonia, and in the case of the genetically dystonic hamster (dt^sz), a model of paroxysmal dystonic choreoathetosis has been used, as these show great promise in contributing to the identification of underlying mechanisms in idiopathic dystonias, although even a proper animal model will probably never be equivalent to a human disease.Several pathophysiological findings from animal models are in line with clinical observations in dystonic patients, indicating abnormalities not only in the basal ganglia and thalamic nuclei, but also in the cerebellum and brainstem. Through clinical studies and neurochemical data several similarities were found in the genetic animal models, although the current data indicates different defects in dystonic animals which is consistent with the notion that dystonia is a heterogenous disorder.Different supraspinal dysfunctions appear to lead to manifestation of dystonic movements and postures. In addition to increasing our understanding of the pathophysiology of idiopathic dystonia, animal models may help to improve therapeutic strategies for this movement disorder.     

不同麻醉方法对28例胃癌手术患者红细胞醛糖还原酶及血浆一氧化氮的影响

目的:观察不同麻醉方法对胃癌手术患者红细胞醛糖还原酶(AR)活性及血浆一氧化氮(NO)浓度的影响。方法:28例胃癌手术患者随机分为两组,组1吸入1.5～2.0最小肺泡吸入有效浓度(MAC)的异氟醚,组2为0.5～1.0MAC异氟醚复合硬膜外麻醉。分别于麻醉前30min、手术90min、术后60min、术后1天和术后2天5个时间点抽取静脉血,测定血糖浓度、红细胞AR活性及血浆NO浓度。结果:与麻醉前值相比,组1病人血糖浓度于手术90min、术后60min、术后1天明显升高(P<0.05或P<0.01);术后1天红细胞AR活性明显升高(P<0.05),同时血浆NO浓度显著下降(P<0.05)。组2病人血糖浓度于手术90min、术后60min显著升高(P<0.01);红细胞AR活性及血浆NO浓度,虽有与组1病人相似的变化趋势,但与麻醉前值相比,各时间点无明显变化。术后1天组1病人红细胞AR活性明显高于组2(P<0.05),而血浆NO浓度则相反(P<0.05),两组间血糖无明显差异。结论:胃癌手术病人在应激高血糖状态下,红细胞多元醇途径被激活的同时血浆NO合成受抑制。全麻联合硬膜外阻滞能较好抑制这一改变。     

大鼠氮能神经与胃电节律失常的关系

目的 :探讨一氧化氮与胃电节律失常的关系 .方法 :2 8只大鼠随机分为 3组 :正常对照组 (12只 )和胃电节律失常模型组 (8只 )喂养 4wk后 ,先记录胃电、再行胃窦肌间神经丛氮能神经染色 ;药物组 (8只 ) :观察注射不同剂量硝普钠 (SNP)、一氧化氮合酶抑制剂左型精氨酸甲酯 (L NAME)后的胃电变化 .结果 :药物组大鼠注射硝普钠或大剂量L NAME后出现了明显的胃电节律失常 ;模型组大鼠胃电节律失常增加 ,异常节律指数 (ARI)和慢波频率变异系数 (coefficientofvariation,CV)分别为 2 1.8%和 2 5 .7% ,明显高于正常对照组大鼠 (ARI和CV分别为 9.5 %和 17.2 % ,P <0 .0 1) ,胃窦肌间神经丛的氮能神经含量也明显多于正常对照组 (2 1.9%vs13.8% ,P <0 .0 1) .结论 :一氧化氮增多或过少均可导致明显的胃电节律失常     

Altered tachykinergic influence on gastric mechanical activity in mdx mice

This study investigated whether alterations in gastric activity in dystrophic mdx mouse can be attributed to dysfunctions of tachykinins. Endoluminal pressure was recorded and the expression of neuronal nitric oxide synthase (nNOS), NK1 and NK2 neurokinin receptors was investigated by immunohistochemistry. SR48968, NK2 receptor antagonist, but not SR140333, NK1 receptor antagonist, decreased the tone only in mdx gastric preparations. In the presence of N(omega)-nitro-l-arginine methyl ester (l-NAME), inhibitor of NOS, SR48968 reduced the tone also in normal stomach. [Sar(9), Met(O(2))(11)]-SP, agonist of NK1 receptors, caused tetrodotoxin-sensitive relaxations, antagonized by SR140333 or l-NAME, with no difference in the potency or efficacy between normal and mdx preparations. [beta-Ala(8)]-NKA(4-10), an NK2 receptor agonist, induced SR48968-sensitive contractions in both types of preparations, although the maximal response of mdx tissues was significantly lower than normal preparations. Immunohistochemistry demonstrated a consistent reduction of nNOS and NK2 receptor expression in mdx stomach smooth muscle cells and no change in nNOS and NK1 receptor expression in neurones. In conclusion, in mdx stomach the activation of NK2 receptors plays a role in the development of the tone, associated with a reduced NO production by muscular nNOS. The hypo-responsiveness to NK2 receptors could depend on the reduced expression of these receptors.     

杜仲对糖尿病大鼠扑捉行为和阴茎组织神经传导通路的影响

目的:探讨杜仲改善勃起功能的药效和病理学机制。方法:雄性糖尿病(DM)大鼠30只随机分为3组:A组(10只,DM大鼠赋形剂灌胃组)、B组(10只,DM大鼠西地那非灌胃组)、C组(10只,DM大鼠杜仲灌胃组)及10只正常对照组大鼠(赋形剂灌胃,D组);灌胃4周后观察4组大鼠扑捉行为,透射电镜检查阴茎组织有髓神经纤维超微特征;用免疫组化二步法显示阴茎组织中神经元型一氧化氮合酶(nNOS)的表达。结果:与A组比较,C组大鼠扑捉次数显著增多(P<0.05),阴茎组织中nNOS表达显著增强(P<0.001)。透射电镜显示:A组大鼠阴茎组织有髓神经纤维排布失序,部分变性、板层分离形成透明空泡或网络状,C组大鼠有髓神经纤维排列规整,板层结构清晰。结论:杜仲可通过减轻有髓神经的损伤、增强阴茎组织中nNOS表达改善ED。