先天性心脏病体外循环术后急性肺损伤患儿磷脂酶A2和白细胞介素6的变化及相关性研究

目的探讨磷脂酶A2（PLA2）和白细胞介素6（IL-6）在婴幼儿先天性心脏病体外循环（CPB）术后发生急性肺损伤（ALI）的变化及意义。方法采用酶联免疫吸附试验（ELISA）方法对10例先天性心脏病体外循环术后急性肺损伤的婴幼儿、10例先天性心脏病体外循环术后未发生急性肺损伤的婴幼儿和10例来我院门诊健康体检婴幼儿进行白介素6检测；同时对上述3组研究对象应用酶底物显色法检测磷脂酶A2活性。结果先天性心脏病体外循环术后急性肺损伤患儿的磷脂酶A2及白介素6均较手术前及体外循环术后无肺损伤的患儿以及健康儿童明显升高，呈显著性差异，P〈0．01。结论磷脂酶如及白介素6在婴幼儿先天性心脏病体外循环术后急性肺损伤中升高，并呈正相关。在婴幼儿先天性心脏病体外循环术后急性肺损伤中，如果能及早应用磷脂酶A：抑制剂或早期干预细胞因子释放，对于阻止肺损伤的进一步发展，以免发生急性呼吸窘迫综合征（ARDS）具有重要意义。     

固尔苏治疗婴儿心脏术后急性肺损伤的观察及护理

随着心脏外科的迅速开展,婴儿体外循环术后长时间呼吸机辅助通气和肺水肿、肺不张、甚至急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)日益引起临床重视。笔者对我院心外ICU的19例病例进行了回顾性总结,以探讨固尔苏应用于婴儿体外循环术后急性肺损伤的护理措施。1临床资料1.1一般     

实验性急性肺损伤一氧化氮氧化产物NO_2~-的变化

一氧化氮（NO）具有强烈的血管扩张作用。由于NO半衰期短，测定较为困难，因此要通过测定一氧化氮氧化产物（NO2-）间接反映NO的含量。为了探索NO在急性肺损伤发病中的作用，我们应用油酸型急性肺损伤模型动态观察NO2-的变化，并用西门子900C呼吸机机械通气，常规容量控制通气（吸呼比为1：2）与反比通气（吸呼比为2：1）比较，结果表明，急性肺损伤各时相点NO2-均高于急性肺损伤前，差异显著（P＜0．05-0．01），但组间差异不明显（P＞0．05）。提示血浆NO增加可能是急性肺损伤继发低血压的一个重要原因。应用一氧化氮合成酶抑制剂抑制一氧化氮的合成，降低一氧化氮的舒血管效应无疑是治疗急性肺损伤继发性低血压的一个新的重要的途径。     

乌司他定对急性肺损伤的治疗作用

机体在遭受各种严重损伤后可引起全身炎症反应综合征（SIRS），导致急性肺损伤（ALI）的发生，肺损伤继续发展可转变为急性呼吸窘迫综合征（ARDS），死亡率高。乌司他定因对炎症介质有显著抑制作用，已被广泛用于体外循环、急性胰腺炎、重症胆管炎等疾病的治疗，取得了一定的疗效。本研究旨在了解乌司他定对急性肺损伤的治疗作用。     

体外循环手术后血浆PAF、IL-8、IFN-γ的变化与急性肺损伤/急性呼吸窘迫综合征的相关性研究

目的体外循环手术后测定血浆血小板激活因子(PAF)、白细胞介素-8(IL-8)、γ-干扰素(IFN-γ)水平变化,分析血浆PAF、IL-8、IFN-γ水平与急性肺损伤/急性呼吸窘迫综合征关系。方法选择2006年12月份至2014年6月份应用体外循环手术治疗的156例患者作为观察对象,其中67例并发急性肺损伤/急性呼吸窘迫综合征,即观察组,另89例未发生急性肺损伤/急性呼吸窘迫综合征作为对照组。在术前、术后1 d、3 d及7 d采用酶联免疫吸附测定法检测血浆中PAF、IL-8及IFN-γ浓度,并对结果进行统计学分析。结果观察组患者手术后血浆PAF、IL-8和IFN-γ浓度明显高于手术前(P0.05);对照组患者手术前后各时段血浆PAF、IL-8和IFN-γ无明显波动(P0.05);观察组血浆PAF、IL-8和IFN-γ浓度明显升高并在术后3 d时达最高值后逐渐下降,但术后各时间的浓度值均显著高于手术前(P0.05);手术后同一时间点相比较,观察组血浆PAF、IL-8和IFN-γ水平显著高于对照组(P0.05)。结论体外循环手术后ALI/ARDS患者血浆PAF、IL-8和IFN-γ变化显著,血浆PAF、IL-8和IFN-γ变化与ALI/ARDS发生关系密切。     

临床乌司他定对急性肺损伤治疗的疗效分析

机体在遭受各种严重损伤后可引起全身炎症反应综合征（SIRS），导致急性肺损伤（ALI）的发生，肺损伤继续发展可转变为急性呼吸窘迫综合征（ARDS），死亡率高。乌司他定因对炎症介质有显著抑制作用，已被广泛用于体外循环、急性胰腺炎、重症胆管炎等疾病的治疗，取得了一定的疗效。本研究旨在了解乌司他定对急性肺损伤的治疗作用。     

体外循环手术后血浆PAF、ⅠL-8、ⅠFN-γ的变化与急性肺损伤/急性呼吸窘迫综合征的相关性研究

目的：体外循环手术后测定血浆血小板激活因子（ PAF）、白细胞介素-8（ⅠL-8）、γ-干扰素（ⅠFN-γ）水平变化,分析血浆PAF、ⅠL-8、ⅠFN-γ水平与急性肺损伤/急性呼吸窘迫综合征关系。方法选择2006年12月份至2014年6月份应用体外循环手术治疗的156例患者作为观察对象,其中67例并发急性肺损伤/急性呼吸窘迫综合征,即观察组,另89例未发生急性肺损伤/急性呼吸窘迫综合征作为对照组。在术前、术后1d、3d及7d采用酶联免疫吸附测定法检测血浆中PAF、ⅠL-8及ⅠFN-γ浓度,并对结果进行统计学分析。结果观察组患者手术后血浆PAF、ⅠL-8和ⅠFN-γ浓度明显高于手术前（ P <0.05）;对照组患者手术前后各时段血浆PAF、ⅠL-8和ⅠFN-γ无明显波动（ P >0.05）;观察组血浆PAF、ⅠL-8和ⅠFN-γ浓度明显升高并在术后3 d时达最高值后逐渐下降,但术后各时间的浓度值均显著高于手术前（ P <0.05）;手术后同一时间点相比较,观察组血浆PAF、ⅠL-8和ⅠFN-γ水平显著高于对照组（ P <0.05）。结论体外循环手术后ALⅠ/ARDS患者血浆PAF、ⅠL-8和ⅠFN-γ变化显著,血浆PAF、ⅠL-8和ⅠFN-γ变化与ALⅠ/ARDS发生关系密切。     

乌司他丁对体外循环过程中肺保护作用的影响

目的体外循环导致急性肺损伤，本研究在体外循环过程中应用乌司他丁后观察肺组织损伤程度的变化，及探讨肺损伤与丝裂原激活蛋白激酶（MAPK）的变化规律的关系。方法100例风湿性心脏病行二尖瓣人工机械瓣置换的病人分为Ⅰ、Ⅱ组。Ⅰ组50例，行常规体外循环，心脏阻断40—55分钟，术中持续肺灌注低温氧合机器血；Ⅱ组50例，体外循环方法同Ⅰ组，在Ⅱ组术中用乌司他丁加低温氧合机器血行肺灌注；分别在不同时段取二组病人血液标本，测量P38MAPK活性，炎症细胞因子IL-6、ID8，及术后气道峰值压力、氧指数等。结果Ⅰ组P38MAPK活性明显增高，Ⅰ组肺损伤与Ⅱ组相比加重（出现统计学差异）。结论体外循环过程中，抑制P38MAPK活性表达可减轻肺损伤，术中应用乌司他丁肺灌注有抑制肺损伤的作用，为体外循环术中肺保护提供一种切实可行的方法。     

Th1/Th2类细胞因子失衡和一氧化氮合酶在内毒素休克性肺损伤中的作用机制

目的　观察内毒素 (LPS)诱导的急性肺损伤 (ALI)大鼠血Th1/Th2类细胞因子浓度以及肺组织一氧化氮合酶 (NOS)活性和NOS基因表达 ,以探讨它们在ALI中的发病机制。方法　采用颈静脉注入LPS复制大鼠急性肺损伤模型 ,用ELISA法检测其外周血单个核细胞产生IFN -γ、IL - 4水平及IFN -γ/IL - 4比值 ;用放射免疫 (RIA)的方法测定LPS注射后大鼠肺组织NOS活性 ;采用逆转录聚合酶链反应 (RT -PCR)检测LPS注射大鼠肺组织内源型一氧化氮合酶 (eNOS)、诱导型一氧化氮合酶 (iNOS)mRNA表达情况。结果　与正常对照组相比 ,急性肺损伤组外周血PBMC产生IFN -γ水平、IFN -γ/IL - 4比值明显升高 (P <0 0 5 ,P <0 0 0 1) ,而IL - 4水平差异无显著性 (P >0 0 5 ) ,同时伴随NOS活性 [( 0 30± 0 0 5 )U/mgpro]明显高于对照组 [( 0 2 4± 0 0 3) ,P <0 0 5 ]。iNOSmRNA表达( 0 70± 0 2 0 )显著高于对照组 (P <0 0 5 ) ,eNOSmRNA表达未见明显变化 (P >0 0 5 )。肺组织病理切片显示大鼠发生ALI。结论　LPS休克肺损伤时 ,体内存在Th1/Th2类细胞因子水平失衡 ,同时伴有NOS活性增高 ,而NOS的主要来源为iNOS基因表达增强     

体外循环状态下血液肿瘤坏死因子α、白细胞介素8、白细胞介素10水平的变化

目的:心脏移植、心脏直视手术过程中的体外循环状态可导致各种炎症介质含量升高,强烈的炎症反应可引起肺损伤.肺开放策略可改善体外循环后肺损伤,观察肺开放策略对体外循环术后呼吸功能及肿瘤坏死因子α、白细胞介素8、白细胞介素10水平的影响.方法:①选择2005-10/2007-10于南通大学第二附属医院心胸外科在全麻、低温、体外循环下行心内直视手术的患者60例,所有患者对实验及治疗方案均知情同意.②将60例患者按随机数字表法分为常规机械通气组、早期肺开放组及晚期肺开放组,每组20例.早期肺开放组在气管插管后实施肺开放策略,晚期肺开放组到达ICU后30 min实施肺开放策略.③应用酶联免疫吸附反应技术于术前、体外循环后及到达ICU后3,5,24,48 h测定血清肿瘤坏死因子α、白细胞介素8、白细胞介素10水平.结果:患者60例全部进入结果分析.①体外循环后各组患者血清肿瘤坏死因子α、白细胞介素8、白细胞介素10水平均较术前显著升高(P < 0.01).②体外循环后早期肺开放组肿瘤坏死因子α水平上升幅度低于晚期肺开放、常规机械通气组(P < 0.01);体外循环后早期肺开放组肿瘤坏死因子α水平逐渐下降,晚期肺开放、常规机械通气组肿瘤坏死因子α水平进一步上升.③血清白细胞介素8水平在期肺开放组、晚期肺开放组呈下降趋势,但常规机械通气组血清白细胞介素8水平各时点均高于术前(P < 0.01).④白细胞介素10水平只在早期肺开放组呈下降趋势.结论:肺开放策略可减少体外循环后炎性细胞因子的释放,从而减轻体外循环相关肺损伤,早期实施肺开放策略优于晚期实施.     

Endothelin-1 and asymmetric dimethylarginine in children with left-to-right shunt after intracardiac repair

BACKGROUND: Endothelin-1 (ET-1) is an endogenous vasoconstrictive peptide hormone and asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of nitric oxide synthase. We hypothesized that both could contribute to pulmonary hypertension in patients with left-to-right shunt after intracardiac repair. PATIENTS AND METHODS: We prospectively analyzed ET-1 and ADMA plasma levels in 31 patients (m = 16; f = 15) at an age of 0.6 [0.2-27] years (median [range]) with left-to-right shunt (ASD II: n = 12; VSD: n = 11; AVSD: n = 8) presenting with a Qp/Qs of 2.7 [1.4-6.3] and a pulmonary arterial mean pressure (PAP) of 23 [13-57] mmHg. Blood specimens were taken prior to cardiopulmonary bypass (CPB), after weaning from CPB and at 3, 6, 12 and 24 h after CPB. RESULTS: 12/31 patients were found to have pulmonary hypertension prior to intracardiac repair and 11/12 patients showed persistent pulmonary hypertension during the first 24 h after CPB. Patients with pulmonary hypertension at 12 h after CPB showed significant higher plasma ET-1 compared with patients with normal PAP (1.4 [0-7.9] versus 0.5 [0-2.5] pg/ml; P = 0.048 (Mann-Whitney)). Plasma ADMA decreased from 1.3 [0.75-2.3] micromol/l before CPB to 0.7 [0.4-2.1] micromol/l at 12 h (P < 0.05). However patients with pulmonary hypertension did not show different ADMA plasma levels. CONCLUSIONS: Increased plasma ET-1 but not inhibition of nitric oxide synthase by ADMA is associated with pulmonary hypertension after intracardiac repair.     

Exhaled nitric oxide level decreases after cardiopulmonary bypass in adult patients

OBJECTIVE: To measure exhaled nitric oxide (NO) and compare it with lung function after cardiopulmonary bypass (CPB) in adult patients. Pulmonary dysfunction is sometimes observed after CPB. Impaired production of NO may account for this dysfunction. DESIGN: Prospective, single-center, observational study. SETTING: University hospital operating room, intensive care unit. PATIENTS: Sixteen adult patients undergoing cardiac surgery with CPB. INTERVENTIONS: None except cardiac surgery with CPB. MEASUREMENTS AND MAIN RESULTS: Exhaled NO was measured continuously by the chemiluminescence method and was expressed as the peak and mean NO concentrations, and the NO output (VNO). These parameters were calculated by averaging four sequential tidal NO values. The data were obtained serially from before CPB to 16 hrs after CPB. Lung function was evaluated by monitoring lung compliance, pulmonary artery pressure, and alveolar-arterial oxygen difference (P(A-a)O2). The cardiac index did not change except for a significant increase at 16 hrs compared with 6 hrs after CPB. Peak NO, mean NO, and VNO decreased from 15.4 +/- 2.0 ppb (before CPB) to 8.2 +/- 0.8 ppb (6 hrs after CPB), from 5.7 +/- 0.7 ppb to 2.8 +/- 0.6 ppb, and from 29.2 +/- 3.1 nL/min to 15.7 +/- 2.2 nL/min, respectively. These changes were associated with the increases in pulmonary artery pressure and alveolar-arterial oxygen difference, and the decrease in lung compliance. VNO recovered to the level measured before CPB 16 hrs after CPB, which was consistent with the physiologic recovery in pulmonary hypertension, lung compliance, and gas exchange. CONCLUSION: Measurement of exhaled NO as VNO, which was associated with lung dysfunction, may be an indicator of lung injury in adult patients after cardiopulmonary bypass.     

急性心肌梗死患者血清血管内皮生长因子与一氧化氮检测的意义

目的:检测急性心肌梗死患者血清血管内皮生长因子和一氧化氮水平,探讨血管内皮生长因子和一氧化氮在急性心肌梗死发病中的作用。方法:选择冠心病患者60例,其中稳定型心绞痛30例,急性心肌梗死30例,健康人30例为对照组,均于入院第1 d抽取空腹静脉血测定血清血管内皮生长因子及一氧化氮的水平。结果:冠心病患者血清中血管内皮生长因子含量明显高于正常对照组(P<0.01);急性心肌梗死组血清中血管内皮生长因子含量明显高于稳定型心绞痛组和正常对照组(P<0.01);冠心病患者血清中一氧化氮含量低于正常对照组(P<0.01),急性心肌梗死患者血清中血管内皮生长因子含量低于稳定型心绞痛组和正常对照组(P<0.01)。结论:冠心病患者血清中血管内皮生长因子含量高而一氧化氮含量低,提示动脉发生粥样硬化的过程中,血管内皮生长因子与一氧化氮相互调节的作用可能发生障碍,血管内皮生长因子与一氧化氮调节失衡可能与动脉粥样硬化发生、发展有关。     

Does the use of leucocyte depletion during cardiopulmonary bypass affect exhaled nitric oxide production?

Fifty patients undergoing elective coronary revascularisation were prospectively randomised to receive either a leucocyte-depleting or a control filter inserted into the arterial line of the cardiopulmonary bypass (CPB) circuit. The concentration of exhaled nitric oxide (NO) was measured 15 min before and 30 min after CPB using a real-time chemiluminescence analyser (Logan Research, Northampton, UK). The baseline rate of exhaled NO production was 2.14 +/- 0.83 ppb/s in the control group, and 2.58 +/- 0.53 ppb/s in leucocyte-depleted group (p = 0.17). Following CPB, the mean rate of exhaled NO production in the control group had increased by 1.51 +/- 0.45 ppb/s to 3.65 +/- 0.81 ppb/s and in the leucocyte- depletion group had increased by 1.05 +/- 0.45 ppb/s to 3.64 +/- 0.62 ppb/s. The increase in exhaled NO production was significantly lower in the leucocyte depleted group (p = 0.002), indicating that leucocyte depletion suppressed the increase in exhaled NO production seen following CPB.     

Leukocyte mitochondrial alterations after cardiac surgery involving cardiopulmonary bypass: clinical correlations

Cardiac surgery with the use of cardiopulmonary bypass (CPB) is known to initiate systemic inflammatory responses that are associated with immune dysregulations, but the pathomechanisms underlying these changes remain elusive. Mitochondrial transmembrane potential (MTP) is an important determinant of leukocytic functions and viability, and may be altered as a part of the cellular responses to systemic inflammatory insults. Therefore, we examined MTP in three subsets of peripheral leukocytes in 18 patients receiving uncomplicated cardiac surgery involving CPB. The MTP of neutrophils and lymphocytes significantly increased, whereas that of monocytes significantly declined, after the surgery. The alterations in leukocytic MTP were transient, normalizing 3 days to 1 week after the surgery, and were accompanied by transient overproduction of intracellular oxidants, including nitric oxide and superoxide. Despite these perturbations, the viability status of leukocytes remained unaltered. Positive correlations were found between the changes of leukocyte MTP and various clinical parameters, implying that leukocyte mitochondrial alterations are parts of the systemic immune perturbations induced by the bypass surgery.     

Inhaled prostacyclin for the treatment of pulmonary hypertension after cardiac surgery

OBJECTIVE: To describe the effects of inhaled prostacyclin administered after cardiopulmonary bypass (CPB) to a patient with severe pulmonary hypertension. DESIGN: Case report and literature review. SETTING: Cardiac surgical operating rooms and postoperative recovery unit. PATIENTS: A 63-yr-old female who had undergone mitral and aortic valve replacement for rheumatic heart disease. INTERVENTIONS: Administration of inhaled prostacyclin to decrease pulmonary artery pressures and to permit discontinuation of CPB. MEASUREMENTS AND MAIN RESULTS: The patient was unable to be removed from CPB because of severe pulmonary hypertension precipitating acute right heart failure, despite administration of milrinone, norepinephrine, and nitroglycerin infusions. Inhaled prostacyclin was started at a dosage of 50 ng/kg/min, and the patient was able to be weaned from CPB. The inhaled prostacyclin was continued for 4 days postoperatively, with no signs of tolerance or systemic effects. CONCLUSION: Inhaled prostacyclin is an effective and selective pulmonary vasodilator at the dosage given in this report. Prolonged use is not associated with tolerance or systemic effects. The apparatus required for the delivery of inhaled prostacyclin is simple, inexpensive, and readily available in most hospitals. A review of the literature suggests that inhaled prostacyclin is effective in a number of clinical settings and displays comparable efficacy and hemodynamic effects to inhaled nitric oxide.     

基质金属蛋白酶-9与婴幼儿体外循环术后急性肺损伤的相关性

目的探讨婴幼儿体外循环心内直视手术对外周血基质金属蛋白酶-9(MMP-9)及其组织抑制剂(TIMP-1)表达水平的影响及MMP-9、TIMP-1在术后急性肺损伤发生、发展中作用。方法随机选择24例房室水平左向右分流型先心病体外循环下行心内直视手术婴幼儿。ELISA法测定血浆MMP-9和TIMP-1水平,RT-PCR法测定外周血白细胞MMP-9mRNA的相对量,免疫荧光观察CPB前和CPB结束时白细胞内MMP-9含量的变化,同时测定CPB前、CPB结束时、CPB结束后1、3、6h肺泡-动脉氧分压差(AaDO2)、呼吸指数(RI)、氧合参数(OI),分析MMP-9和MMP-9/TIMP-1比值与呼吸功能指标之间的相关性。结果(1)CPB后1、3、6、24h血浆MMP-9的水平与CPB前相比明显升高,差异具有统计学意义(P<0.01),其中CPB结束后3h血浆MMP-9浓度达到最高峰;(2)CPB后1、3、6、24h血浆TIMP-1的浓度与CPB前相比明显下降,差异具有统计学意义(P<0.01),其中CPB结束后3h血浆TIMP-1的浓度达到最低值;(3)CPB后1、3、6、24h血浆MMP-9/TIMP-1比值与CPB前相比明显升高,差异具有统计学意义(P<0.01),其中CPB结束后3h达到最大值;(4)CPB结束时、CPB结束后6、24h外周血白细胞MMP-9mRNA的相对量与CPB前相比明显增加,差异具有统计学意义(P<0.01);(5)CPB结束时、CPB后1、3、6hAaDO2、RI与CPB前相比明显升高,差异具有统计学意义(P<0.01),而OI与CPB前相比则明显下降,差异具有统计学意义(P<0.01)。结论婴幼儿体外循环心直视手术后外周血MMP-9血浆水平和MMP-9mRNA转录水平明显增加,而血浆TIMP-1浓度明显下降,血浆MMP-9浓度和活性与婴幼儿体外循环心直视手术后急性肺损伤指标密切相关。外周血中MMP-9过度表达和MMP-9/TIMP-1比例失衡在婴儿体外循环手术后急性肺损伤形成过程中发挥重要作用。     

Role of controlled cardiac reoxygenation in reducing nitric oxide production and cardiac oxidant damage in cyanotic infantile hearts.

Cardiopulmonary bypass (CPB) is used increasingly to correct cyanotic heart defects during early infancy, but myocardial dysfunction is often seen after surgical repair. This study evaluates whether starting CPB at a conventional, hyperoxic pO2 causes an "unintentional" reoxygenation (ReO2) injury. We subjected 2-wk-old piglets to ventilator hypoxemia (FIO2 approximately 0.06, pO2 approximately 25 mmHg) followed by 5 min of ReO2 on CPB before instituting cardioplegia. CPB was begun in hypoxemic piglets by either abrupt ReO2 at a pO2 of 400 mmHg (standard clinical practice) or by maintaining pO2 approximately 25 mmHg on CPB until controlling ReO2 with blood cardioplegic arrest. The effects of abrupt vs. gradual ReO2 without surgical ischemia (blood cardioplegia) were also compared. Myocardial nitric oxide (NO) production (chemiluminescence measurements of NO2- + NO3-) and conjugated diene (CD) generation (spectrophotometric A233 measurements of lipid extracts) using aortic and coronary sinus blood samples were assessed during cardioplegic induction. 30 min after CPB, left ventricular end-systolic elastance (Ees, catheter conductance method) was used to determine cardiac function. CPB and blood cardioplegic arrest caused no functional or biochemical change in normoxic (control) hearts. Abrupt ReO2 caused a depression of myocardial function (Ees = 25 +/- 5% of control). Functional depression was relatively unaffected by gradual ReO2 without blood cardioplegia (34% recovery of Ees), and abrupt ReO2 immediately before blood cardioplegia caused a 10-fold rise in cardiac NO and CD production, with subsequent depression of myocardial function (Ees 21 +/- 2% of control). In contrast, controlled cardiac ReO2 reduced NO production 94%, CD did not rise, and Ees was 83 +/- 8% of normal. We conclude ReO2 injury is related to increased NO production during abrupt ReO2, nullifies the cardioprotective effects of blood cardioplegia, and that controlled cardiac ReO2 when starting CPB to correct cyanotic heart defects may reduce NO production and improve myocardial status postoperatively.     

高胆固醇血症环境下注射造影剂诱发急性肾功能衰竭

目的：探讨高胆固醇血症是否是造影剂肾损害的促进因素。方法：24只雄性Wistar大鼠随机分成两组，分别给予正常饮食(N组)和高胆固醇饮食（H组，4％胆固醇和1％胆酸钠）8周。8周末从N组和H组中各取半数大鼠（6只）尾静脉注射60％泛影葡胺（6ml/kg，NC组和HC组），另半数大鼠尾静脉注射等量生理盐水。注射造影剂后的第二天测定血清总胆固醇、甘油三酯、血肌酐、内生肌酐清除率、肾皮质一氧化氮的含量；彩色多普勒和频谙式多普勒测定肾血流；光镜观察肾组织学改变。结果：HC组和H组血清总胆固醇及肾血管阻力指数显著性增加，而内生肌酐清除率、肾皮质一氧化氮含量显著性降低。HC组的内生肌酐清除率显著低于H组，HC组的血清肌酐、钠钾排泄分数显著高于其它三组。组织病理也显示HC组大鼠肾小管上皮细胞发生严重变性和坏死，而NC组和H组大鼠仅见肾小管变性。结论：高胆固醇血症是造影剂肾损害的促进因素；肾皮质一氧化氮含量的减少可介导了高胆固醇血症环境下造影剂诱导的急性肾功能衰竭。     

Lack of alteration of endogenous nitric oxide pathway during prolonged nitric oxide inhalation in intensive care unit patients

OBJECTIVE: To compare hemodynamic and gasometric variables and the plasma concentrations of nitric oxide metabolites (cyclic guanosine monophosphate and nitrate and nitrite), endothelin-1, and renin-angiotensin metabolites before and after the start of nitric oxide inhalation, after prolonged nitric oxide inhalation, and before and after nitric oxide withdrawal. DESIGN: Prospective study. SETTING: Surgical intensive care unit, university hospital. SUBJECTS: Patients with acute lung injury and right ventricular failure. INTERVENTIONS: Nitric oxide inhalation (10-12 ppm) during a median of 2.9 days (12 hrs to 6.5 days). MEASUREMENTS AND MAIN RESULTS: The pulmonary vasodilator effects of inhaled nitric oxide improved arterial oxygenation in patients with acute lung injury (p < .05) and reduced right atrial pressure in patients with right ventricular dysfunction (p < .01). These beneficial effects lasted the whole period of prolonged inhaled nitric oxide therapy up to 6.5 days. However, when inhaled nitric oxide was withdrawn, pulmonary vasodilator effects rapidly disappeared, and Pao2/Fio2 ratio markedly deteriorated in all studied patients to return to pre-inhaled nitric oxide levels. Changes in plasma cyclic guanosine monophosphate and nitrate and nitrite paralleled those of pulmonary vasodilatory effects. An immediate increase in plasma cyclic guanosine monophosphate with a slightly delayed increase in plasma nitrate and nitrite was observed at inhaled nitric oxide start with no attenuation during the prolonged inhaled nitric oxide therapy. A marked decrease toward pre-inhaled nitric oxide levels was seen within hours of inhaled nitric oxide withdrawal. In addition, no alteration of plasma endothelin-1 or renin-angiotensin mediators was observed during or after inhaled nitric oxide therapy. CONCLUSIONS: Our study showed a lack of attenuation in the beneficial effects of inhaled nitric oxide and a lack of alteration of endogenous nitric oxide, endothelin-1, and renin-angiotensin pathways during prolonged nitric oxide inhalation.