Plasma endothelin-1 and nitric oxide correlate with ligustrazine alleviation of pulmonary artery hypertension in patients of chronic cor pulmonale from high altitude plateau during acute exacerbation

Objective To explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension(PAH) in patients of chronic obstructive pulmonary disease(COPD) associated with chronic cor pulmonale(CCP) during exacerbation.Methods Seventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group.The control group received standard treatment with antibiotics,antiasthmatic and expectorant medications,and oxygenation;and the ligustrazine treatment group received ligustrazine treatment(80 mg/d;i.v.;for 2 weeks) in addition to the standard treatment.Before and at the end of 2 week treatment,the clinic responses of the two regimens were evaluated,plasma levels of endothelin-1(ET-1) and nitric oxide(NO) were determined;arterial oxygen partial pressure(PaO_2),mean pulmonary arterial pressure(mPAP),outflow tract of right ventricle(RVOT),and internal diameter of right ventricle(RV) were measured.Results Good clinic benefits were achieved in both the standard and ligustrazine regimens,plasma level of ET-1,values of mPAP,RV and RVOT decreased significantly,plasma level of NO and PaO_2 values decreased(all P<0.01 vs pretreatment to all parameters).Compared with the control group,ligustrazine greatly enhanced the clinic efficacy from 77.1%to 97.1%(P<0.05),and also resulted in more significant changes of all these parameters(P<0.01 vs control group for all parameters).For both groups,the levels of plasma ET-1 were positively correlated with values of mPAP,RVOT,and RV(r = 0.710,0.853,and 0.766,respectively,all P = 0.000),and negatively correlated with plasma NO and PaO_2(r =- 0.823,and- 0.752,respectively,all P = 0.000).Conclusion Ligustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area.The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells,thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.

Inhibition of Expression of Hypoxia-inducible Factor-1α mRNA by Nitric Oxide in Hypoxic Pulmonary Hypertension Rats

In order to study the effect of nitric oxide (NO) on the expression of hypoxia inducible factor 1 alpha (HIF 1α) mRNA in hypoxic pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic control group, chronic hypoxic group and hypoxia plus L argine (L Arg) group. The animal model of HPH was developed. The mean pulmonary arterial pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The HIF 1α mRNA expression levels were detected by in situ hybridization (ISH) and semiquantitative RT PCR. It was found that after 14 days hypoxia, the mPAP in normoxic control group (17.6±2 7 mmHg,1 mmHg=0 133 kPa) was significantly lower than that in chronic hypoxic group(35.8±6.1 mmHg, t =0.2918, P <0.05) and mPAP in chronic hypoxic group was higher than that in hypoxia plus L argine group(24.4±3.8 mmHg, t =0.2563, P <0.05). ISH showed that the expression of HIF 1α mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic control group (0.1076±0.0205) was markedly weaker than that in chronic hypoxic group (0.3317±0.0683, t =3.125, P <0.05) and that in chronic hypoxic group was stronger than that in hypoxia plus L argine group (0.1928±0.0381, t =2.844, P <0.05). RT PCR showed that the content of HIF 1α mRNA in chronic hypoxic group (2.5395±0.6449) was 2.16 times and 1.75 times higher than that in normoxic control group (1.1781±0.3628) and hypoxia plus L argine group (1.4511±0.3981), respectively. It is concluded that NO can reduce the mPAP by the inhibition of the expression of HIF 1α mRNA, which may be one of the mechanisms through which NO affects the pathogenesis of HPH.

Effect of stellate block on vasomotor factor, vascular endothelial nitricoxide synthase and pulmonary arterial pressure in rabbits with hypoxic pulmonary artery hypertension

BACKGROUND： At present, inhalation of nitrogen monoxidum （NO） or other angiotenic is widely used to cure hypoxic pulmonary artery hypertension. In addition, recent researches demonstrate that postganglionic fiber of stellate ganglion can regulate contents of blood vessel endothelium-calcitonin gene-related peptide （BVE-CGRP） and nitricoxide synthase （NOS） in lung tissue. Therefore, stellate ganglion which is blocked with the local anesthetic may cause therapeutic effects on hypoxic pulmonary artery hypertension. OBJECTIVE： To observe the effects of stellate block on calcitonin gene-related peptide （CGRP） of vasodilation factors, prostacyclin, endothelin-i of vasoconstriction factors, thromboxan, blood vessel endothelium-nitricoxide synthase （BVE-NOS） and mean arterial pressure of lung tissue in rabbits with hypoxic pulmonary artery hypertension. DESIGN： Randomly controlled animal study. SETTING： Neurological Institute of Taihe Hospital Affiliated to Yunyang Medical College. MATERIALS： A total of 24 adult Japanese rabbits of both genders and weighing 2.3 - 2.6 kg were provided by Animal Experimental Center of Hubei Academy of Medical Science. SP kit was provided by Beijing Zhongshan Biotechnology Co., Ltd.; moreover, kits of endothelin-1, CGRP, prostacyclin and thromboxan were provided by Radioimmunity Institute, Scientific and Technological Developing Center, General Hospital of Chinese PLA, and color image analytical system （Leica-Q500IW） was made in Germany. METHODS：The experiment was carried out in the Neurological Institute of Taihe Hospital affiliated to Yunyang Medical College from February to December 2002. ① Rabbits were performed with aseptic manipulation to exposure left stellate ganglion and then it was put in epidural catheter for 1 week. In addition, one end of epidural catheter was fixed near by stellate ganglion and the other end was fixed through dorsal neck. All rabbits were randomly divided into 4 groups, including normal control group, stellate block group, hypoxia group and hypoxia ＋ stellate block group, with 6 in each group. Rabbits in the normal control group were perfused with saline through epidural catheter with 0.5 mL once for three times per day and 3 successive days in total; in addition, rabbits in the stellate block group were perfused with 2.5 g/L bupivacaine through epidural catheter with 0.5 mL once for three times per day and 3 successive days in total. Rabbits in the hypoxia group were used to establish hypoxic pulmonary artery hypertension models. That was to say, the experimental rabbits were put in hypoxic box （containing sodalime and calcium chloride to absorb CO2 and water） and given various flows of oxygen and nitrogen through the two lateral wells simultaneously. And then, oxygen was monitored with oxygen-concentration monitoring device to control the concentration in （10±2）% for 8 hours per day and 2 successive weeks in total. Rabbits in the hypoxia ＋ stellate block group were used to establish hypoxia models as the same as those in the hypoxia group. Two weeks later, 2.5 g,/L bupivacaine was pushed into epidural catheter with 0.5 mL once for three times per day and 3 successive days in total. Breast was directly opened to measure mean pulmonary artery pressure.② 6 mL blood was collected through pulmonary arterial duct to measure levels of plasma CGRP, prostacyclin, endothelin-I and thromboxane with radio-immunity technique; meanwhile, immunohistochemical staining was used to observe the changes of BVE-NOS content of the experimental rabbits in all groups. MAIN OUTCOME MEASURES： Changes of CGRP, prostacyclin, endothelin-1 and thromboxane and BVE-NOS. RESULTS： A total of 24 experimental rabbits were involved in the final analysis. ①As compared with those in the normal control group, hypoxic pulmonary artery hypertension of the experimental rabbits was higher in the hypoxia group and hypoxia ＋ stellate block group after hypoxia [（3.8±0.30）, （3.16±0.45）, （2.60± 0.27） kPa, P 〈 0.05, 0.01]; CGRP was lower [（68.20 ±8.78）, （108.24 ±14.35）, （130.25 ±22.70） ng/L, P 〈 0.05, 0.01]; prostacyclin was lower [（94.45± 10.68）, （98.77± 12.31）, （155.27±20.67） ng/L, P 〈 0.01]; endothelin-1 was higher [（184.7±29.66）, （115.27± 13.62）, （98.20±11.52）, ng/L, P 〈 0.05, 0.01]; thromboxan was higher [（226.27 ±30.46）, （207.67 ±27.32）, （124.25 ± 16.89） ng/L, P 〈 0.01 ]. As compared with that in hypoxia group, hypoxic pulmonary artery hypertension was decreased in hypoxia ＋ stellate block group （P 〈 0.05）, CGRP was increased （P 〈 0.01）, and endothelin-1 was decreased remarkably （P 〈 0.05）. ② Level of BVE-NOS of the experimental rabbits was higher in stellate block group, hypoxia group and hypoxia ＋ stellate block group than that in the normal control group [（0.25±0.06）, （0.27±0.07）, （0.46± 0.12）, （0.14±0.03）, P 〈 0.05], and NOS level was higher in the hypoxia ＋ stellate block group than that in hypoxia group （P 〈 0.05）. CONCLUSION： Mean arterial pressure is decreased in rabbits with hypoxic pulmonary artery hypertension after stellate block and level of endothelin-1 is also decreased; however, levels of CGRP and NOS are increased respectively.

Methylene blue could transiently reverse the vasodilator effect of inhaled nitric oxide in canine hypoxic pulmonary hypertension mode

Low dose inhalation of nitric oxide could selectively lower pulmonary hypertension. But increasing methemoglobin (MeHb) formation is one of its side effects. This study aimed to investigate whethermethylene blue (MB) could attenuate the therapeutic effect of nitric oxide (NO) while reducing methemoglobin.Methods: The effect of administering MB 2 mg.kg-1 intravenously on mean pulmonary arterial pressure (MPAP)was observed after the inhalation of 90±7 vpm (volume per million) NO in nine dogs with pulmonary hypertension induced by hypoxia (FiO2=0.08). Results: Inha1ation of NO significantly decreased MPAP (P<0.01) from 2. 6±0.9kPa to 2.0±0.6 kPa. After intravenous administration of MB, the pulmonary vasodilator effect of inhaled NO (P<0.01) was partly reversed, MPAP increased from 2. 01±0. 6 kPa to 2. 3±0. 7 kPa, and cardiac output (CO) significantly increased (P<0. 05). But the effects lasted on1y 5 min. Couclusion: MB could transiently and partly reverse the pulmonary vasodilator action of inhaled NO in canine hypoxic pulmonary hypertension mode.The MB should be carefully used in severe pulmonary hypertension.

Correlation between endothelia cells activation and imbalance of cytokines in pulmonary hypertension of congenital heart disease

Objective To explore the correlation between endothelia cells activation and cytokines (ET-1, NO) levels in patients with pulmonary hypertension (PH), and to discuss their roles in the development of PH. Methods Twenty patients with simple ventricular septal defect (VSD) were chosen as controls, and 30 patients with PH were studied. Plasma levels of ET-1 and NO were measured by radioimmunoassay or colorimetric method. Before cardiopulmonary bypass was established, the specimens from right lung were fixed with formaldehyde solution, embedded with paraffin and stained by SP immunohistochemistry. Intercellular adhesion molecule-1 (ICAM-1) expression was measured through the determination of the light density with computer imaging technology. Results Compared with that of the patients with simple VSD, the light density of ICAM-1 and plasma level of ET-1 increased in patients with PH; but plasma level of NO decreased (P<0.05). Positive correlation was observed between ICAM-1 and ET-1/NO (P<0.05). Conclusion Endothelia cells activation and imbalance of ET-1/NO might play an important role in the development of PH.

Comparison of inhaled milrinone, nitric oxide and prostacyclin in acute respiratory distress syndrome

AIM To evaluate the safety and efficacy of inhaled milrinone in acute respiratory distress syndrome(ARDS).METHODS Open-label prospective cross-over pilot study where fifteen adult patients with hypoxemic failure meeting standard ARDS criteria and monitored with a pulmonary artery catheter were recruited in an academic 24-bed medico-surgical intensive care unit. Random sequential administration of i NO(20 ppm) or nebulized epoprostenol(10 μg/mL) was done in all patients. Thereafter, inhaled milrinone(1 mg/mL) alone followed by inhaled milrinone in association with inhaled nitric oxide(iN O) was administered. A jet nebulization device synchronized with the mechanical ventilation was use to administrate the epoprostenol and the milrinone. Hemodynamic measurements and partial pressure of arterial oxygen(PaO_2) were recorded before and after each inhaled therapyadministration.RESULTS The majority of ARDS were of pulmonary cause(n = 13) and pneumonia(n = 7) was the leading underlying initial disease. Other pulmonary causes of ARDS were: Post cardiopulmonary bypass(n = 2), smoke inhalation injury(n = 1), thoracic trauma and pulmonary contusions(n = 2) and aspiration(n = 1). Two patients had an extra pulmonary cause of ARDS: A polytrauma patient and an intra-abdominal abscess Inhaled nitric oxide, epoprostenol, inhaled milrinone and the combination of inhaled milrinone and i NO had no impact on systemic hemodynamics. No significant adverse events related to study medications were observed. The median increase of PaO 2 from baseline was 8.8 mmH g [interquartile range(IQR) = 16.3], 6.0 mm Hg(IQR = 18.4), 6 mm Hg(IQR = 15.8) and 9.2 mm Hg(IQR = 20.2) respectively with i NO, epoprostenol, inhaled milrinone, and i NO added to milrinone. Only i NO and the combination of inhaled milrinone and i NO had a statistically significant effect on PaO 2. CONCLUSION When comparing the effects of inhaled NO, milrinone and epoprostenol, only NO significantly improved oxygenation. Inhaled milrinone appeared safe but failed to improve oxygenation in ARDS.

Assessment of Reversibility in Pulmonary Hypertension Related to Congenital Heart Disease by Using Biomarkers and Clinical Features

Background:Reversibility of pulmonary hypertension(PH)is closely related to the treatment options for and prognosis of children with congenital heart disease.Objective:We combined patient-specific clinical features including diagnosis,age and echocardiographic results,and biomarkers of pulmonary vascular dysfunction to explore the noninvasive methods that can be used to accurately evaluate the reversibility of pulmonary hypertension in congenital heart disease(PH-CHD).Methods:Based on the preoperative systolic pulmonary arterial pressure(sPAP),70 CHD patients were divided into normal,PH-CHD suspected,and confirmed groups.Additionally,biomarkers of circulating endothelial cells(CECs),endothelin-1(ET-1),and endothelial nitric oxide synthase(eNOS)were detected.Patients were categorized into reversible(RPH)and irreversible(IRPH)groups according to the sPAP 6 months after surgery.Risk stratification was performed according to the clinical features and biomarkers.Results:CECs and ET-1 levels in the confirmed group were significantly higher.eNOS was higher in the confirmed and suspected groups than that in the normal group.CECs in the IRPH group were significantly higher compared to the RPH group.No such intergroup differences were observed with respect to ET-1 and eNOS levels.The ROC curve showed that the risk stratification was of high diagnostic value to evaluate reversibility.Conclusion:The CECs,eNOS,and ET-1 were closely related with PH-CHD.CECs and risk stratification have high practical value in assessing the reversibility of PH-CHD.

硝化应激在肺动脉高压中的研究进展

肺动脉高压(pulmonary hypertension,PH)是一种进行性发展的肺血管疾病,病理基础包括内皮功能障碍、平滑肌细胞异常增生、炎症浸润以及肺纤维化。PH的发生机制尚不完全清楚,但硝化应激已经证实在PH中发挥了重要作用。该文综述了活性氮(reactive nitrogen species,RNS)的种类及肺循环中RNS的来源,以及由此引发的硝化应激在PH发生发展中的作用,以期为靶向抗硝化治疗的临床应用提供参考依据。

早期联合应用外源性PS和iNO治疗PPHN的效果

目的探讨早期联合应用外源性肺表面活性物质(PS)和吸入一氧化氮(iNO)治疗新生儿持续性肺动脉高压(PPHN)的效果。方法选取2019年1月1日至2021年12月31日收治的100例PPHN患儿为研究对象,按照随机数字表法将其分成对照组和观察组,各50例。对照组应用iNO+安慰剂(空气),观察组应用iNO+外源性PS。比较两组的治疗效果。结果治疗前,两组的肺动脉收缩压(PASP)、氧分压(PaO_(2))、二氧化碳分压(PaCO_(2))、pH及氧合指数(OI)比较,差异无统计学意义(P>0.05);治疗24、48 h后,两组的PASP、PaCO_(2)、OI均降低,PaO_(2)及pH均升高,且观察组优于对照组,差异具有统计学意义(P<0.05)。观察组的治愈率明显高于对照组,应用体外氧合膜肺(ECMO)及死亡率低于对照组,呼吸机使用时间及总住院时间短于对照组,差异具有统计学意义(P<0.05);两组的不良反应发生情况比较,差异无统计学意义(P>0.05)。结论早期联合应用外源性PS和iNO可明显改善PPHN患儿的氧合情况、降低PASP,减少呼吸机使用时间、总住院时间、对ECMO需求及死亡率,值得临床推广应用。

NO缓释纳米粒子PEG-b-PAASNO对肺动脉平滑肌细胞的影响

目的:探讨一氧化氮(NO)供体聚合物胶束PEG-b-PAASNO(PSNO)对肺动脉平滑肌细胞(PASMC)的影响。方法:构建PSNO并检测体外释放NO水平。分离并培养大鼠PASMC,CCK8确定PSNO安全浓度范围和有效作用浓度。设立空白对照组、PSNO(250 ng·mL^(-1))组(PSNO组)、血小板衍生生长因子-BB(PDGF-BB,15 ng·mL^(-1))组(BB组)和PDGF-BB+PSNO(15 ng·mL^(-1)PDGF-BB+250 ng·mL^(-1)PSNO)组(BB+PSNO组),用5-乙炔基-2′脱氧尿嘧啶核苷(EDU)实验、划痕实验和Transwell实验评估PSNO对PASMC增殖、迁移能力的影响,免疫印迹法评估PASMC增殖、收缩、细胞周期相关蛋白[增殖细胞核抗原(PCNA)、钙调蛋白(calponin)、α-平滑肌肌动蛋白(α-SMA)、细胞周期蛋白D1(cyclin D1)、周期蛋白依赖性激酶2(CDK2)]的表达水平。组间比较采用one-way ANOVA分析。结果:成功构建稳定释放NO的纳米聚合物胶束PSNO,连续释放NO超过48 h,效应呈时间-剂量依赖性。PSNO质量浓度为250 ng·mL^(-1)时有效抑制PDGF-BB诱导的PASMC增殖、迁移;与BB组相比,BB+PSNO组PCNA、calponin、α-SMA、cyclin D1和CDK2蛋白表达水平降低,差异均有统计学意义(P<0.05)。结论:成功构建一种可以稳定释放NO的纳米聚合物胶束PSNO,其有效释放NO超48 h,功能上阻滞PASMC增殖、迁移,并降低PASMC收缩、细胞周期相关蛋白表达水平。

新生儿持续肺动脉高压患儿血清CXCL8、CXCL12与一氧化氮吸入治疗临床转归的关系

目的探讨新生儿持续肺动脉高压(persistent pulmonary hypertension of newborn,PPHN)患儿血清人CXC型趋化因子配体8(C-X-C motif chemokine ligand 8,CXCL8)、CXCL12与一氧化氮吸入治疗临床转归的关系。方法选择2021-08/2023-05月作者医院收治并给予一氧化氮吸入治疗的PPHN患儿135例为研究对象。根据患儿出院时临床转归结局分为死亡组(n=32)和存活组(n=103)。比较两组PPHN患儿血清CXCL8、CXCL12水平。单因素及多因素Logistic回归模型分析接受一氧化氮吸入治疗PPHN患儿临床转归的影响因素。受试者工作特征(receiver operating characteristic,ROC)曲线分析血清CXCL8、CXCL12对接受一氧化氮吸入治疗PPHN患儿临床转归的预测价值。结果死亡组患儿血清CXCL8、CXCL12水平显著高于存活组(P均<0.05)。多因素Logsitic回归分析结果显示,血清CXCL8水平升高、血清CXCL12水平升高、早产、出生时Apgar评分0~3分、合并并发症是接受一氧化氮吸入治疗的PPHN患儿死亡的危险因素,肺表面活性物质应用、吸入一氧化氮早期反应则是保护因素(P<0.05)。ROC曲线分析结果显示,血清CXCL8、CXCL12联合检测对接受一氧化氮吸入治疗的PPHN患儿死亡预测的曲线下面积(area under the curve,AUC)为0.828,大于血清CXCL8、CXCL12单独检测(AUC分别为0.762、0.714)。结论PPHN患儿血清CXCL8、CXCL12水平升高与接受一氧化氮治疗的不良临床转归有关,且CXCL8、CXCL12水平升高是PPHN患儿死亡的危险因素。CXCL8、CXCL12联合检测对接受一氧化氮治疗PPHN患儿死亡具有较高的预测价值。

高频振荡通气联合一氧化氮吸入对早产儿持续肺动脉高压疗效以及氧合指数的影响

目的:探究高频振荡通气联合一氧化氮吸入在早产儿持续肺动脉高压中的应用效果。方法:按随机数字表法将2022年8月至2023年10月我院新生儿重症监护室(NICU)收治的持续肺动脉高压早产儿分为对照组(30例),观察组(30例)。对照组采用高频振荡通气治疗,观察组加用一氧化氮吸入联合治疗,比较两组临床疗效、血气指标、肺动脉收缩压、机械通气时间、住院时间及并发症情况。结果:观察组总有效率(96.67%)高于对照组(73.33%),P<0.05;治疗后,观察组动脉血氧分压(PaO_(2))水平高于对照组,P<0.05;动脉血二氧化碳分压(PaCO_(2))、吸入氧浓度(FiO_(2))、氧合指数(OI)水平低于对照组,P<0.05;肺动脉收缩压(SPAP)水平低于对照组,P<0.05;经皮血氧饱和度(SpO_(2))水平高于对照组,P<0.05;观察组机械通气时间与住院时间均短于对照组,P<0.05;两组并发症发生率均较低。结论:高频振荡通气联合一氧化氮吸入在早产儿持续肺动脉高压中治疗效果确切,可有效改善患儿血气指标,促进通气,还可缩短住院时间,且并发症少,安全性较好,值得推广。

Interaction between en- dogenous nitric oxide and carbon monoxide in the pathogenesis of hypoxic pulmonary hypertension

The aim of the study was to investigate the in-teraction between nitric oxygenase (NOS)/ nitric oxide (NO) and heme oxygenase (HO)/ carbon monoxide (CO) system in the pathogenesis of hypoxic pulmonary hypertension. On a rat model of hypoxic pulmonary hypertension, the pulmo-nary artery pressure was measured, and NO formation and expression of NOS in pulmonary tissues were examined after treatment with ZnPP-IX, an HO-1 inhibitor. The pulmonary artery pressure, CO formation and expression of HO-1 in pulmonary tissues were examined after treatment with L-NAME, a NOS inhibitor. We found that pulmonary hy-pertension developed after 2-week hypoxia, while the con-centration of NO in the pulmonary tissue homogenates and the expression of NOS in intrapulmonary artery endothelial cells decreased markedly. ZnPP-IX worsened pulmonary hypertension of hypoxic rats. However, it increased endoge-nous production of NO and the expression of NOS obviously. The concentration of CO in the pulmonary tissue homoge-nates and the expression of HO-1 in intrapulmonary artery smooth muscle cells increased markedly with hypoxic pul-monary hypertension. L-NAME worsened pulmonary hy-pertension of hypoxic rats, but inhibited CO formation and HO-1 expression (P < 0.01). The results of this study sug-gested that endogenous NOS/NO and HO/CO systems might interact with each other and therefore play an important regulating role in hypoxic pulmonary hypertension.

Hemodynamic Effects of Inhaled Nitric Oxide in Patients with Pulmonary Hypertension.

Twelve patients with pulmonary hypertension (primary pulmonary hypertension in 3 cases, secondary to recurrent pulmonary embolism in 4 cases, chronic obstructive pulmonary disease in 2 cases and complicated with congeni-

Reversal of Acute Hypoxic Pulmonary Hypertension with Inhalation of Nitric Oxide.

The effect of inhalation of nitric oxide（NO）gas on acute hypoxic pulmonary hypertension was studied.Eighteen mongrel dogs were divided into two groups; hypoxic control group（FIO=11％， n=10）and NO inhalation gloup（FIO=11％，NO inspiratory concentration=44ppm，n=8）.

经CPAP呼吸机吸入NO治疗新生儿持续性肺动脉高压的临床研究

目的探讨应用经鼻持续正压通气(CPAP)吸入一氧化氮(NO)治疗新生儿持续性肺动脉高压(PPHN)的疗效及安全性。方法选取枣庄市妇幼保健院2017年6月至2022年5月新生儿监护室收治的经超声心动图确诊为PPHN的新生儿36例为研究对象,应用CPAP吸入NO,疗程到患儿撤离NO;记录吸入NO前后动脉血氧分压,血氧饱和度、血压、心率等,同时监测二氧化氮(NO_(2))、高铁血红蛋白数值(MHb),血小板和凝血功能。结果吸入NO前氧分压与经皮血氧饱和度低于吸入NO后1、24 h,差异有统计学意义(P<0.05);吸入NO前心率、血压、血小板及活化部分凝血活酶时间(APTT)与吸入NO后1、24 h比较,差异无统计学意义(P>0.05);36例患儿吸入N01、24、48、72 h后的MHb含量均<3%,NO_(2)浓度均<2.0 ppm,均在安全范围。结论经CPAP呼吸机吸入NO治疗PPHN安全有效。

NO吸入治疗肺血管适应不良性新生儿持续肺动脉高压的临床疗效

目的探究一氧化氮(NO)吸入治疗肺血管适应不良性新生儿持续肺动脉高压(PPHN)的效果。方法选取2018年1月至2022年12月深圳市新生儿数据协作网所属医院(多中心)新生儿病房收治的68例肺血管适应不良性PPHN患儿为研究对象,根据是否使用NO吸入治疗分为未吸入NO组(38例)和吸入NO组(30例)。未吸入NO组予常规对症支持治疗,吸入NO组在常规对症支持治疗基础上联合低浓度NO吸入治疗。比较两组治疗前与治疗1周左右的血气分析指标,包括动脉血氧饱和度(SaO_(2))、动脉血氧分压(PaO_(2))、动脉血二氧化碳分压(PaCO_(2))、血pH值;治疗前后的肺动脉收缩压(PASP)、体循环收缩压(SBP)、左心室射血分数(LVEF)、氧合指数(OI),治疗1周后的疗效,以及不良反应发生情况。结果吸入NO组机械通气时间短于未吸入NO组[6.0(4.0,8.3)d比9.5(7.0,13.0)d](P<0.01)。治疗前,吸入NO组血pH值低于未吸入NO组,PaCO_(2)高于未吸入NO组(P<0.05),余各项血气指标水平比较差异无统计学意义(P>0.05)。治疗1周后,两组SaO_(2)、PaO_(2)、pH值均较治疗前明显升高,PaCO_(2)较治疗前明显降低(P<0.05),且吸入NO组SaO_(2)、PaO_(2)、pH值明显高于未吸入NO组,PaCO_(2)明显低于未吸入NO组(P<0.05)。治疗前,吸入NO组PASP、PASP/SBP高于未吸入NO组(P<0.01),两组SBP比较差异无统计学意义(P>0.05)。治疗1周后,两组PASP、PASP/SBP均较治疗前明显降低,吸入NO组SBP较治疗前升高(P<0.05),且吸入NO组PASP、PASP/SBP明显低于未吸入NO组,SBP水平明显高于未吸入NO组(P<0.05)。治疗前,两组LVEF、OI比较差异无统计学意义(P>0.05)。治疗1周后,两组OI以及吸入NO组LVEF均较治疗前明显升高(P<0.01),且吸入NO组LVEF、OI明显高于未吸入NO组[(0.68±0.06)%比(0.65±0.05)%、280(226,369)mmHg比250(142,280)mmHg](P<0.05)。治疗1周后,吸入NO组治疗总有效率明显高于未吸入NO组[96.67%(29/30)比78.95%(30/38)](χ^(2)=4.584,P=0.032)。吸入NO组疗效优于未吸入NO组(Z=3.166,P=0.002)。治疗期间,对照组和观察组不良反应总发生率比较差异无统计学意义[21.05%(8/38)比20.00%(6/30)](χ^(2)=0.011,P=0.915)。结论NO吸入联合机械通气及血管扩张剂治疗能有效改善肺血管适应不良PPHN患儿的pH、PaCO_(2)和PaO_(2),并降低肺动脉压力,改善氧合,效果优于单纯机械通气和血管扩张剂药物治疗,且不良反应发生率未增加,安全性较高。

一氧化氮与肺动脉高压及基于一氧化氮信号通路的肺动脉高压治疗药物研究进展

一氧化氮(NO)是一种重要的血管舒张因子,具有调节血管平滑肌舒张、抑制血管平滑肌细胞增殖及减少血小板聚集和血栓形成的功能,参与调节肺动脉高压的发生发展,改善肺动脉高压。为实现NO持续、受控释放和靶点特异性,大量研究致力于开发纳米载体系统递送NO供体,用于肺动脉高压的日常给药治疗。本文概述了体内NO来源及其舒血管作用机制,总结了目前针对NO信号通路的3种肺动脉高压靶向治疗药物(磷酸二酯酶5抑制剂、鸟苷酸环化酶激动剂和吸入性NO),介绍了代表性的NO供体(如有机硝酸盐、金属亚硝基化合物、亚硝酸盐和N-重氮鎓二酸盐)以及治疗肺动脉高压的纳米载体制剂(直接递送NO气体的纳米粒子、基于亚硝酸盐的NO递送系统和基于N-重氮鎓二酸盐的NO递送系统)的研究进展。

外周血Apelin、NO、NOS水平对慢阻肺急性加重期并发肺动脉高压的诊断价值

目的探讨外周血Apelin、一氧化氮(NO)、一氧化氮合酶(NOS)水平对慢阻肺急性加重期(AECOPD)并发肺动脉高压(PH)的诊断价值。方法选取2018年3月至2021年7月重症医学科收治的139例AECOPD患者设为AE组,同期选取门诊随诊的144例慢阻肺稳定期患者设为稳定期组,另选150例健康体检者设为对照组,检测外周血Apelin、NO、NOS水平。根据AE组超声心动图检测结果将其分为PH并发组和未并发组,分析AECOPD患者并发PH的影响因素,并评估血清指标对AECOPD患者并发PH的诊断价值。结果AE组和稳定期组外周血Apelin、NO、NOS水平均低于对照组(P<0.05),且AE组以上指标水平均更低(P<0.05);并发组外周血Apelin、NO、NOS水平均低于未并发组(P<0.05);吸烟史、氧分压降低、二氧化碳分压升高与第1s用力呼气容积占预计值百分比、第1s用力呼气容积/用力肺活量、外周血Apelin、NO、NOS水平降低均是AECOPD患者并发PH的危险因素(P<0.05);外周血Apelin、NO、NOS水平联合诊断AECOPD并发PH的灵敏度、曲线下面积均高于单独诊断(P均<0.05),其特异度与单独诊断无显著差异(P均>0.05)。结论AECOPD并发PH患者外周血Apelin、NO、NOS水平降低,与AECOPD患者并发PH有关,能帮助临床预测PH的发生。