Comparison of inhaled nitric oxide with aerosolized prostacyclin or analogues for the postoperative management of pulmonary hypertension: a systematic review and meta-analysis

Abstract

Background: This study aims to compare the effectiveness of inhaled prostacyclin or its analoguesversus nitric oxide (NO) in treating pulmonary hypertension (PH) after cardiac or pulmonary surgery remains unclear.

Methods: PubMed, Cochrane, and Embase databases were searched for literature published prior to December 2019 using the following keywords: inhaled, nitric oxide, prostacyclin, iloprost, treprostinil, epoprostenol, Tyvaso, flolan, and pulmonary hypertension. Randomized controlled trials and multiple-armed prospective studies that evaluated inhaled NO versus prostacyclin (or analogues) in patients for perioperative and/or postoperative PH after either cardiac or pulmonary surgery were included. Retrospective studies, reviews, letters, comments, editorials, and case reports were excluded.

Results: Seven studies with a total of 195 patients were included. No difference in the improvement of mean pulmonary arterial pressure (pooled difference in mean change= ?0.10, 95% CI: ?3.98 to 3.78, p?=?.959) or pulmonary vascular resistance (pooled standardized difference in mean change= ?0.27, 95% CI: ?0.60 to 0.05, p?=?.099) were found between the two treatments. Similarly, no difference was found in other outcomes between the two treatments or subgroup analysis.

Conclusions: Inhaled prostacyclin (or analogues) was comparable to inhaled NO in treating PH after cardiac or pulmonary surgery.

• Key messages

• This study compared the efficacy of inhaled prostacyclin or its analogues versus inhaled NO to treat PH after surgery. The two types of agent exhibited similar efficacy in managing MPAP, PVR, heart rate, and cardiac output was observed.

• Inhaled prostacyclin may serve as an alternative treatment option for PH after cardiac or pulmonary surgery.

     

Revisiting the Hydrogen Storage Behavior of the Na-O-H System

Solid-state reactions between sodium hydride and sodium hydroxide are unusual among hydride-hydroxide systems since hydrogen can be stored reversibly. In order to understand the relationship between hydrogen uptake/release properties and phase/structure evolution, the dehydrogenation and hydrogenation behavior of the Na-O-H system has been investigated in detail both ex- and in-situ. Simultaneous thermogravimetric-differential thermal analysis coupled to mass spectrometry (TG-DTA-MS) experiments of NaH-NaOH composites reveal two principal features: Firstly, an H₂ desorption event occurring between 240 and 380 °C and secondly an additional endothermic process at around 170 °C with no associated weight change. In-situ high-resolution synchrotron powder X-ray diffraction showed that NaOH appears to form a solid solution with NaH yielding a new cubic complex hydride phase below 200 °C. The Na-H-OH phase persists up to the maximum temperature of the in-situ diffraction experiment shortly before dehydrogenation occurs. The present work suggests that not only is the inter-phase synergic interaction of protic hydrogen (in NaOH) and hydridic hydrogen (in NaH) important in the dehydrogenation mechanism, but that also an intra-phase H^δ+… H^δ– interaction may be a crucial step in the desorption process.     

Kombucha tea ameliorates experimental autoimmune encephalomyelitis in mouse model of multiple sclerosis

Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS), in which an inflammatory demyelination and axonal damage occurs. Kombucha tea is a fermented beverage made from kombucha mushroom, brewed tea, and sugar. In recent years kombucha tea has attracted interest due to its pharmacological properties like antioxidant effects. The aim of the present research was to test the therapeutic effect of kombucha tea in EAE. We induced EAE model in 18 female C57BL/6 mice by inoculation of myelin oligodendrocyte glycoprotein-35-55 (MOG_35-55) in complete Freund’s adjuvant emulsion. Then, in order to ameliorate EAE symptoms, we used kombucha tea. During the course of study clinical evaluation was assessed, and on the day 21 post-immunization, for evaluation of nitric oxide (NO), total antioxidants capacity and tumor necrosis factor-alpha (TNF-α), blood samples were taken from the heart of mice. The mice were sacrificed and brains and cerebellums of mice were removed for histological analysis. Our findings demonstrated that kombucha tea had beneficial effects on EAE by lower incidence, attenuation in the severity, and also a delay in the onset of disease. Histological analysis showed that inflammatory criteria including the number of infiltrated immune cells and plaques as well as demyelination in kombucha tea dosed mice were significantly lower than the control group. Also, in comparison with control mice, the serum levels of NO and TNF-α in kombucha tea-treated mice were significantly decreased. Kombucha tea with its potential therapeutic effects and immunomodulatory properties might be proposed, after additional necessary tests and trials, for treatment of MS.     

一氧化氮合酶在外阴慢性单纯性苔藓和外阴硬化性苔藓中的表达

目的：检测诱导型和内皮型一氧化氮合酶（iNOS 和eNOS）在外阴慢性单纯性苔藓和外阴硬化性苔藓中的表达。方法：采用免疫组织化学SABC法检测iNOS和eNOS在30例外阴慢性单纯性苔藓蜡块（LSC）、30例外阴硬化性苔藓蜡块（LS）和10例外阴正常皮肤中的表达，并以人原始造血细胞抗原（CD34）标记微血管内皮细胞，测量各组织的微血管密度（MVD）。结果：iNOS和eNOS在外阴正常皮肤中无表达；在LSC中iNOS和eNOS每视野平均阳性细胞数分别为14.83±3.79和17.86±4.82，高于LS的8.00±3.35和6.43±3.87，差异均有统计学意义（P＜0.05）；在LSC和正常皮肤中MVD分别为21.58±2.48和20.44±3.66，高于LS（10.34±2.83）。iNOS和eNOS的表达具有明显的正相关性（Kappa=0.811，P＜0.05）。结论：iNOS和eNOS可能与LSC炎症过程中的血管扩张有关；在LS皮损真皮中微血管减少，iNOS和eNOS可代偿性地改善LS的血液循环。     

谷氨酸对腺苷A2A受体调节一氧化氮合酶活力的影响

目的探讨谷氨酸是否能够影响腺苷A2A受体对一氧化氮合酶（NOS）活力的调节。方法用1000ng／ml脂多糖（LPS）刺激小胶质细胞，分别加入100nmol／L A2A受体激动剂CGS21680以及不同浓度的谷氨酸（0，1，0，25，0，5mmol／L）干预，观察NOS活力变化。结果LPS诱导NOS活力增高，激活A2A受体可以产生抑制作用；0，25及0．5mmoL／L谷氨酸和A2A受体激动剂同时存在时，NOS活力进一步增高。结论高浓度谷氨酸可逆转腺苷A2A受体激动剂抑制升高NOS活力的作用。     

硫化氢及一氧化氦气体信号分子在高原高血压发病中的作用

目的 探讨气体信号分子硫化氢（H2S）及一氧化氮（NO）在高原高血压的病理生理意义。方法 平原体检正常者进入海拔5000m高原（1～3）月期间，在高原暴露时间、劳动强度及生活条件相同的施工群体中随机抽样127人。依血压变化将其分为高原高血压（Ⅰ～Ⅲ级）组78人（进一步分为收缩期高原高血压组与舒张期高原高血压组），高原正常血压组49人，采取肘静脉血，采用敏感硫电极法测定其H2S浓度，Griess法测定血清NO含量。结果 高原高血压组、收缩期高原高血压组、舒张期高原高血压组的血清H2S与NO平均含量均显著增加，分别比正常血压组高34．5％，36．9％，31.7％（均P〈0．001）与28．4％，33．1％，39．7％，（均P〈0．05），尤以H2S更为突出；随着血压分级程度的升高H2S与NO血清含量相应增高，也以H2S更显著（R^2=0．918）；H2S与NO、舒张压间均有密切正相关关系及良好的拟和优度、与氧饱和度呈显著的负相关与拟和优度（R^2=0．374，P=0．001）。结论 H2S与NO的代谢失常可能参与了高原高血压发病过程。     

角膜碱烧伤房水一氧化氮及一氧化氮合酶变化

目的探讨角膜碱烧伤后房水一氧化氮（NO）与炎症反应的关系。方法用健康家兔动态观察对照组、实验组和对侧眼组眼内炎症反应及房水一氧化氮合酶（NOS）和NO2^-／NO3^-的活性。结果角膜碱烧伤后炎症反应与房水NOS和NO活性呈动态变化，实验组明显高于对侧眼组，且两组均高于对照组。结论房水NO的变化与角膜碱烧伤后的眼内炎症反应密切相关。     

衰老对大鼠阴茎组织NO-cGMP通路及端粒酶活性的影响研究

目的探讨衰老对大鼠阴茎组织结构、NO(nitric oxide)-cGMP(cvclic Guanosine Monophosphate)通路及端粒酶活性的影响作用。方法本课题以不同月龄大鼠阴茎组织及培养的平滑肌细胞为研究对象,检测不同月龄大鼠阴茎组织中NO量、NOS(Nitric Oxide Synthase)活性、cGMP量、端粒酶活性及海绵体结构的变化,并比较大鼠、人阴茎组织及大鼠原代海绵体平滑肌细胞的端粒酶活性。结果(1)大鼠阴茎组织中NO量、NOS活性均先升高后降低,各月龄组间有显著差异。阴茎组织cGMP含量逐渐降低,各月龄组间差别显著；(2)随龄增加,平滑肌纤维逐渐减少,胶原纤维增多,粗大成团,窦状隙变少、变窄：(3)大鼠阴茎组织端粒酶活性以2月龄活性最高,随龄增加逐渐下降。人阴茎组织中无端粒酶活性。结论(1)衰老对大鼠阴茎组织结构、NO．cGMP通路及端粒酶活性有显著影响,提示衰老与ED关系密切；(2)大鼠阴茎组织有端粒酶活性,可作为研究细胞衰老与ED关系有关端粒酶的模型。     

氯胺酮对大鼠丘脑一氧化氮合酶活性和一氧化氮含量的影响

目的：观察不同剂量的氯胺酮对大鼠丘脑一氧化氮合酶（NOS）和一氧化氮（NO）含量的影响。方法：Sprague Dawley(SD)大鼠32只，雌雄不限，体重200－300g。随机分为四组（n=8):组I为对照组，给予生理盐水10ml/kg腹腔注射；组Ⅱ、组Ⅲ和组Ⅳ分别给予氯胺酮35ml/kg,100ml/kg和200ml/kg。组I和组Ⅱ在用药后5min后断头取材，组Ⅲ和组Ⅳ在大鼠翻正反射消失后立即断头取材。在低温操作箱内生理盐水冰面上取脑，以分光光度法测定NOS活性和NO量，Lawry法测蛋白含量。结果：大鼠腹腔注射氯胺酮35ml/kg后，其丘脑的NOS活性和NO量与对照组相比均无明显变化（P＞0．05）而腹腔注射氯胺酮100ml/kg和200ml/kg后，NOS活性明显降低，分别较对照组降低了44．3％和40％（P＜0．05）和P＜0．01），NO量也明显减少，分别较对照组减少了42．9％和47．1％（P＜0．05）或（P＜0．01）；且这两组的NOS活性和NO量也明显低于氯胺酮35ml/kg组，NOS活性分别降低了47．3％和43．2％（P＜0．01），NOS量降低了47．4％和51．3％（P＜0．01）；此两组之间相比较，丘脑的NOS活性和NO量无统计学意义（P＞0．05）。结论：NO在氯胺酮的中枢作用机制中可能发挥重要作用。