深呼吸时三级支气管内吸气流动特性的数值研究

剧烈运动时,人体要通过深呼吸,为机体组织及器官的快速新陈代谢过程补充足够的氧气,研究深呼吸时人体肺内气体的流动及输运机理,对运动生理学及临床医学具有理论意义和临床价值.采用有限体积法数值,求解Navier-Stokes方程组,数值研究深呼吸情况下,人体三级支气管模型内的吸气流动规律,比较了均匀及抛物型速度进气条件对支气管内流动分布的影响.结果表明:深呼吸时,支气管内出现了复杂的流动现象,包括主流的射流-尾流结构及m-型结构,以及二次流的2涡向4涡结构演变过程,与平静及正常呼吸状态相比,深呼吸使肺内中部及侧部下游支气管内流量分流不均匀性加重,压力损失急剧增大,支气管内壁承受更大的气动负荷.     

无心跳供体肺支气管内气体三维流动的数值模拟研究

无心跳供体肺（NHBD）有望解决临床供肺严重不足的问题,肺内低温通气被公认为是NHBD肺在体低温保护的有效方法之一,可提高供肺的利用率。通过建立三维非对称四级支气管模型,运用计算流体动力学(CFD)方法对支气管内的气流流动特性进行数值模拟,并通过试验对数值模拟的边界条件进行验证。研究结果表明：在被动呼吸的吸气和呼气时,支气管截面上的无量纲速度分布不同,左肺支气管和右肺支气管截面上的速度分布也存在较大差异,其中左肺下叶支气管内中心线上的无量纲速度峰值最大,达到1.7,而右肺上叶支气管内中心线上的无量纲速度峰值最小,仅为0.8;由于分叉角度和管径不同,导致吸气过程中流入左主支气管内和右主支气管内的流量分别占55%和45%,而左肺下叶支气管内的流量比率在各肺叶支气管内的流量比率最高,约为35%;通过分析支气管内的流动压力损失,得出支气管的平均压降系数与Re的关系为p∝Re^－0.6。可见,由于支气管的非对称结构以及分叉处空间旋转角度的存在,使得支气管内的气体流动结构比较复杂,这对于无心跳供体肺原位通低温保存的临床实验研究有一定的参考价值。     

弯曲圆管入口段定常流动的三维数值模拟

目的 研究定常流动条件下弯曲圆管入口段内的流动情况。方法 用有限体积法对弯曲圆管入口段定常流动作三维数值模拟。结果 分别计算了管内流线、截面等速度线、沿对称面直径的速度剖面和壁面切应力分布等。沿对称面直径的速度剖面计算值与实验结果吻合很好。结论 弯管的外侧壁是高切应力区，内侧壁是低切应力区，证实内侧壁是动脉粥样斑块的高发区。     

循环吸气支气管内瞬态气流运动特性的仿真研究

人体支气管内的瞬态气流运动对气溶胶在支气管内的沉积产生重要影响,深入认识支气管内的瞬态气流运动特性,对于分析气溶胶在人体支气管内的沉积模式具有重要作用。应用计算流体动力学方法,对人体轻度运动强度下Weibel模型的3级到6级支气管内的瞬态气流运动特性进行了数值仿真,讨论了支气管对称平面、横截面内的瞬态气流组织形式。研究结果表明:在支气管的对称平面内,支气管分叉处产生气流分离现象;在吸气加速阶段,在3级支气管横截面内,没有产生涡流运动;在吸气加速阶段,4级支气管内,呈现出具有内壁附近区域速度高、外壁区域附近速度低的倾斜的抛物线特点的速度分布形式;5级支气管内,形成由两个涡流到四个涡流又到两个涡流的涡流演变过程。在6级支气管横截面内,在吸气加速阶段,和4级支气管横截面相似,在对称平面上下形成两个对称旋转的涡流运动,两个涡流中心分别处于上下平面的中心位置。     

急性呼吸窘迫综合征患者下呼吸道内气流运动特性

目的应用计算流体动力学(computational fluid dynamics,CFD)技术对急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)患者不同程度呼吸窘迫状态时下呼吸道内气流运动特性进行模拟研究。方法基于CT影像数据建立真实健康人体下呼吸道三维模型。采用标准k-ε湍流模型对下呼吸道内的气体流动进行数值模拟,分析下呼吸道内气流的速度、流量、压力以及壁面剪切应力等参数分布特点。结果拟合下呼吸道空气流动阻力与呼吸强度的函数关系;得到下呼吸道内空气流速、压力、壁面剪切应力的分布特点以及空气流量在各肺及各叶支气管的分配情况。结论通过CFD模拟分析可以获得更为详细的下呼吸道流场相关数据,为ARDS患者的临床治疗提供理论依据。     

不同入口流量波形对颈动脉分叉壁面切应力的影响

目的 研究不同颈总动脉生理流量波波形对颈动脉分叉壁面切应力的影响。方法 建立颈动脉分叉TF-AHCB数值模型。用Womersley方法求解Bloch和Holdsworth两种经典的血液流量波形的速度分布,并作为入口条件用CFD软件计算分叉管内流场和壁面切应力分布。结果 两种波形在颈动脉分叉根部外侧壁形成的低切应力区相仿,但具有较低重搏波波谷的Holdsworth波形使局部振荡剪切因子明显增大。Holdsworth波形产生的振荡剪切因子是Bloch波形产生的1.75倍,局部最高值可达0.49。结论 在对动脉分叉管血流动力学数值或实验模拟中,正确设定入口流量波形和速度剖面条件是重要的。     

呼吸道内颗粒物沉积的数值模拟

目的通过数值模拟方法研究人呼吸过程中吸入的颗粒物在呼吸道内的沉积规律及其影响因素。方法建立正常人呼吸道三维数值模型,模拟吸气过程中气流在呼吸道内的分布规律。在鼻孔或口等气流入口处释放颗粒,模拟悬浮颗粒物随着吸入气流在呼吸道内的沉积过程。同时改变颗粒物直径、密度、呼吸气流速率等参数,通过对比分析,研究颗粒物在呼吸道内沉积的影响因素。结果颗粒物在呼吸道内主要沉积在鼻阈、固有鼻腔气道中部、鼻咽部以及支气管内壁,并且颗粒物的沉积率随着其直径、密度、呼吸气流速率的增大而增加,几个参数对沉积率的影响程度也不相同。结论颗粒物在呼吸道内主要沉积在气道几何形状复杂或者气道走向剧烈改变的位置,颗粒物的直径、密度、呼吸气流速率均会影响到其在呼吸道内的沉积率。研究结果可为空气污染引发呼吸道疾病风险的临床评估提供数值依据。     

两房室神经元模型的分岔现象

目的神经元放电模式的研究一直是计算神经科学领域的研究热点。方法本文运用非线性动力学方法,理论分析了在不同电生理参数改变的情况下,一类双房室锥体神经元模型中可能存在的各种周期放电模式以及不同放电模式之间的转移,并对模式转移过程中出现的各种非线性分岔现象做了深入探讨。结果数值分析结果揭示了该两房室神经元信息传导过程中的倍周期分岔现象。不仅得到复杂的放电节律序列,并且发现了分岔序列结构。结论为更进一步认识神经元模型中复杂多样的放电模式和不同模式转移中所出现的周期分岔结构提供了线索。     

上气道内流动现象与压力分布模拟

目的用计算流体力学模拟的方法和体外模型实验的手段,研究呼吸时真实结构的上气道内的流动状态和压力分布,同时验证数值模拟模型的准确性。方法首先基于磁共振图像,借助Mimics软件重建上气道三维结构。在此真实几何结构基础上,建立上呼吸道内流动的有限元分析模型,以及制作相应的实体模型。模拟并测量呼吸流量为200、400和600 m L/s时的情况,并将数值模型预测的壁面压力分布与实测结果比较。结果如果气道内气流流量相同,吸气时气道两端的压差比呼气时大,即吸气时气道阻力比呼气时大。不同点压力分布的数值计算结果与实体模型测量结果一致。数值模拟结果表明,吸气时气道悬雍垂以及会厌后的舌后区域流动速度较高,悬雍垂下舌后区有涡旋产生。呼气时矢状位鼻咽顶端靠近后壁处,冠状位鼻咽、会厌下口咽处均有涡旋产生。结论数值模型可以准确地模拟上气道的流动状态和压力分布,直观地反映上气道内流动特点。作为非侵入式的工具,气道模型和数值模拟可以在探索阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)的发病机制和有效治疗方法的过程中发挥重要作用。     

上气道及部分支气管生物力学模型的数值研究

目的建立上气道、气管及部分支气管的生物力学模型,研究不同呼吸模式对气道内气流特性以及气道阻力的影响。方法根据CT扫描资料,建立包括鼻腔、口腔、咽、喉、气管和部分支气管在内的具有真实解剖结构形态的三维有限元呼吸道模型,针对现实中几种典型情况,数值模拟流经鼻、口的气流不同比例情况下气道内的气流特性。结果当仅有少量气流经由口腔吸入时,呼吸道内气流的分布规律以及各部位气道阻力的大小与完全经由鼻腔呼吸的情况相似。当口腔吸入或呼出大量气体,气流主要经由口腔与外界进行交换时,呼吸道内气流场、压力场和剪应力场分布规律明显不同,主要区别体现在鼻腔、口腔气道内。结论建立上气道与气管、支气管生物力学模型,可以从整体上了解呼吸过程中整个上气道至部分支气管中气流的分布情况,为了解与上气道结构相关疾病的发病机制建立数值研究平台。     

The effect of inlet velocity profile on the bifurcation COPD airway flow

The effect of inlet velocity profile on the flow features in obstructed airways is investigated in this study. In reality, the inlet velocity distributions on such models, which are extracted from medial branches of natural human lung, should be neither uniform, nor symmetric parabolic, but skewed-parabolic due to having been skewed by the upper carina ridges. Four different three-dimensional three-generation models based on the 23 generations model of Weibel have been considered, respectively. The fully three-dimensional incompressible laminar Navier-Stokes equations and continuity equation have been solved using CFD solver on unstructured tetrahedral meshes. To reduce the complexity of the simulations, only one Reynolds number of 900 was used in this calculation. Four types of inlet boundary conditions, namely uniform, parabolic, positive-skewed parabolic (skewed to the positive x-direction), and negative-skewed parabolic, were imposed on the obstructed airway models, which were considered to be obstructed at either the second generation or the third generation airways, respectively. The results show that the inlet velocity profile has significant influence on the flow patterns, mass distributions, and pressure drops in either the symmetric model, or the three obstructed models. The three generation airways may not be enough to study the bifurcation flow in chronic obstructive pulmonary disease (COPD) airways, and a four-generation or more airway model is necessary to get better predictive results.     

Pathologic changes in the small airways of the guinea pig after amosite asbestos exposure

To determine whether asbestos dust produces pathologic changes in the small airways, and to determine where the anatomic lesions of asbestosis commence, the authors examined lungs from guinea pigs exposed to 10 or 30 mg of amosite asbestos by intratracheal instillation and sacrificed 6 months later. Measurement of airway wall thickness revealed that membranous and respiratory bronchioles of all sizes in exposed animals were significantly thicker than those of controls. Amosite fibers were found embedded in the walls of bronchi and in membranous and respiratory bronchioles; where these fibers penetrated the airway walls, an interstitial inflammatory and fibrotic reaction (asbestosis) occurred. It is concluded that 1) amosite asbestos produces diffuse abnormalities throughout the noncartilagenous airways and possibly the cartilagenous airways as well; 2) this effect is independent of interstitial fibrosis of the parenchyma (classical asbestosis); 3) asbestosis, at least that induced by amosite, commences at any site in the parenchyma to which the asbestos fibers can gain access, either by deposition in alveoli and alveolar ducts or by direct passage of fibers through the walls of all types and sizes of small airways.     

Location of flow limitation in liquid-filled rabbit lungs

The effects of end-inspiratory lung volume (EILV) and expiratory flow rate (Q) on the location of flow limitation in liquid-filled lungs were investigated by measuring pressure along the airways and by radiographic imaging. The lungs of New Zealand white rabbits were filled with perfluorocarbon to the randomly selected EILV of 20, 30, or 40 ml/kg, and the volume was actively drained at one of three Q: 2.5, 5.0, or 7.5 ml/s. The minimum pressures recorded by a movable catheter at locations along the airways show that flow limitation occurred in the main bronchi and trachea, and was independent of EILV and Q. The minimum pressure at the trachea was -80 mm Hg compared with values that were more positive than -10 mm Hg at a location 3 cm distal to the carina for all EILV and Q combinations. This location was confirmed by the lung images. The airway diameters gradually decreased with time, until flow limitation occurred. In airways distal to the collapse, there was not a significant decrease in diameter. Based on these data, we conclude that flow limitation in liquid-filled lungs occurs in the trachea and main bronchi and its location is independent of EILV or Q.     

Forced perturbation of respiratory system

The conventional model of the respiratory system is based on an electric analog of an LRC-circuit, or a mechanical analog of a mass-spring-damper system characterized by inertance, resistance, and complicance. The meaning of the three constants, L, R, and C must be related to the airway geometry, elasticity, and boundary conditions. In order to clarify this basic relationship, we remove the restriction of one degree of freedom and present an analysis of the respiratory system as a continuous elastic body. The extra- and intralobular airways, the lung parenchyma, the chest wall, the diaphragm muscle, and the abdominal organs are considered separately. The governing equations are linearized by considering small perturbations. In the case of a small pressure pulse applied at the mouth, the expansion of the airways and the resulting flow are computed. The results indicate that a predominant effect of the forced oscillation test is the expansion of the extralobular airways. The resistance computed from the experimental data according to the LRC-circuit analog depends strongly on theelastic properties of the airway walls, as well as the pressure drop in the upper airway due to viscous friction and turbulence in the flow.     

Geometric determinants of airway resistance in two isomorphic rodent species

The flow resistance of the pulmonary airway tree (Raw) is disproportionately larger in large animals than in smaller ones. This is thought to be due to the fact that smaller animals have relatively wider central airways than larger animals. However, Raw is not determined solely by the diameter of the main bronchi or trachea. It depends on the dimensions of all the individual airways and how they are connected. We investigated how the degree of asymmetry of the airway tree, the number of airway orders, and dimensions of the individual airways combine to determine Raw. We performed this investigation using computer models of the airway trees of two different sized isomorphic rodents that differ in weight by more than two orders of magnitude-the harvest mouse and the giant pouched rat. We calculated airway resistance in these models under various conditions, and confirmed that the smaller species has a lower Raw relative to body size than the larger species. We also showed that these differences are due to a combination of differences both in relative airway diameters and in the degree of asymmetry of the airway trees.     

Tracheobronchial epithelium in the adult rhesus monkey: A quantitative histochemical and ultrastructural study

Previous studies of the intrapulmo-nary conducting airways of sheep and rabbit have demonstrated marked diversity in the epithelial populations lining them. Because studies of trachea and centriaci-nar regions of macaque monkeys suggested that primates may be even more diverse, the present study was designed to characterize the epithelial population throughout the airway tree of one primate species, the rhesus monkey. Trachea and intrapulmonary airways of the right cranial and middle lobes of glutaraldehyde/ paraformaldehyde-infused lungs of five adult rhesus monkeys were microdissected following the axial pathway. Each branch was assigned a binary number indicating its specific location within the tree. The trachea and six generations of intrapulmonary airway from the right cranial lobe were evaluated for ultrastructure and quantitative histology as were those of the right middle lobe for quantitative carbohydrate histochemistry. Four cell types were identified throughout the tree: ciliated, mucous goblet, small mucous granule, and basal. The tallest epithelium lined the trachea; the shortest, the respiratory bronchiole. The most cells per unit length of basement membrane were in proximal intrapulmonary bronchi; the least, in the respiratory bronchiole. The nonciliated bronchiolar epithelial or Clara cell was restricted to respiratory bronchioles. Sulfomucins were present in the vast majority of surface goblet cells in the trachea and proximal bronchi. In proximal bronchi, neutral glycoconjugates predominated in glands and acidic glycoconjugates in surface epithelium. In terminal and respiratory bronchioles the ratio of acidic gly-coconjugate to neutral glycoconjugate equaled that in proximal bronchi, although glands were not present. Sulfomucins were minimal in terminal airways. We conclude that the characteristics of the epithelial lining of the mammalian tracheobronchial airway tree are very species-specific. The lining of the rhesus monkey does not have the diversity in cell types in different airway generations observed in sheep and rabbit. Also, the populations lining these airways in the rhesus are very different from either the sheep or rabbit in number, proportions of different cell types, glycoconjugate content, and distribution of specific cell types.     

A Simulation Study of Expiratory Flow Limitation in Obstructive Patients during Mechanical Ventilation

Although normal lungs may be represented satisfactorily by symmetrical architecture, pathological conditions generally require accounting for asymmetrical branching of the bronchial tree, since lung heterogeneity may be significant in respiratory diseases. In the present study, a recently proposed symmetrical dynamic morphometric model of the human lung, based on Weibel’s regular dichotomy, was adapted to simulate different physiopathological scenarios of lung heterogeneity. The asymmetrical architecture was mimicked by modeling different conductive airway compartments below the main bronchi, each compartment being characterized by regular branching. The respiratory zone and chest wall were described by a Voigt body and a constant elastance, respectively.Simulation results allowed us to investigate the influence of the main mechanisms involved in expiratory flow limitation and dynamic hyperinflation in mechanically ventilated COPD patients. In brief, they showed that convective gas acceleration plays a key role in reproducing a negative relationship between driving pressure and expiratory flow. Moreover, reduced lung elastance due to emphysema resulted in a remarkable increase in dynamic hyperinflation, although it did not significantly modify expiratory flow limitation. Finally, the presence of a normal lung compartment masked pathological behaviors, preventing standard techniques from revealing expiratory flow limitation in affected compartments.     

Fetal nicotine exposure increases airway responsiveness and alters airway wall composition in young lambs

To test the hypotheses that fetal nicotine exposure alters airway wall composition and enhances the airway response to inhaled methacholine (MCh), lambs were exposed during the last fetal trimester to (1) a low dose (LN) (n=13, 0.5mg/kg/d (maternal weight) of free base nicotine, (2) a moderate dose (MN) (n=10, 1.5mg/kg/d) or (3) saline (n=14). Studies were performed at postnatal days 12, 26 and 52. Prenatal nicotine exposure induced a dose- and age-related hyper-responsiveness to MCh in the proximal airways. Moment analysis of nitrogen decay curves showed no nicotine or MCh effects on ventilation homogeneity or gas-mixing efficiency in the distal airways during MCh inhalations suggesting a bimodal response. Fetal nicotine exposure increased epithelial mucosubstance volume in central (LN, MN) and distal bronchi (LN), increased smooth muscle volume in distal bronchi and bronchioles (LN) and decreased bronchiolar diameter (MN). In conclusion, third trimester nicotine exposure causes hyperreactive proximal airways and alters proximal airway wall composition associated with airflow limitation.     

Ozone-induced acute tracheobronchial epithelial injury: relationship to granulocyte emigration in the lung.

To investigate the relationship between granulocyte emigration and epithelial injury in specific airway generations of the tracheobronchial tree following short-term ozone exposure, we exposed rhesus monkeys for 8 h to 0.00 (controls) or 0.96 ppm ozone with post-exposure periods of 1, 12, 24, 72, and 168 h in filtered air before necropsy. There were five control and three exposed monkeys for each of the post-exposure times for a total of 20 monkeys. Neutrophils isolated from peripheral blood and labeled with 111In-tropolonate were infused in the cephalic vein in unanesthetized monkeys (except the 1-h group) 4 to 5 h before necropsy. The trachea and microdissected bronchi (fourth and ninth generations) and respiratory bronchioles (fifteenth generation) from the right upper lobe of each monkey were examined by electron microscopy. Labeled neutrophil influx into lung tissue and bronchoalveolar lavage fluid (BALF) was maximal at 12 h and returned to baseline by 24 h after exposure. This was in contrast to total neutrophils (labeled and unlabeled) in BALF, which were significantly elevated through 24 h after exposure but returned to baseline by 72 h. Lavage protein was significantly elevated at 24 h after exposure but was at control levels at all other times. Morphometric observations showed epithelial necrosis at 1 and 12 h in the trachea and bronchioles but continued to be observed in significant numbers at 24 h after exposure in bronchi. A significant increase in the labeling index of epithelial cells was observed at 12 h only in bronchi. Epithelial necrosis and repair was associated with the presence of granulocytes in the epithelium and interstitium of all airway levels. However, eosinophils were maximally increased in the epithelium and interstitium of bronchi at 24 h after exposure when epithelial necrosis was maximal in these airways and when lavage protein was significantly elevated.(ABSTRACT TRUNCATED AT 250 WORDS)