A pre-operative planning for endoprosthetic human tracheal implantation: a decision support system based on robust design of experiments

Swallowing depends on physiological variables that have a decisive influence on the swallowing capacity and on the tracheal stress distribution. Prosthetic implantation modifies these values and the overall performance of the trachea. The objective of this work was to develop a decision support system based on experimental, numerical and statistical approaches, with clinical verification, to help the thoracic surgeon in deciding the position and appropriate dimensions of a Dumon prosthesis for a specific patient in an optimal time and with sufficient robustness. A code for mesh adaptation to any tracheal geometry was implemented and used to develop a robust experimental design, based on the Taguchi's method and the analysis of variance. This design was able to establish the main swallowing influencing factors. The equations to fit the stress and the vertical displacement distributions were obtained. The resulting fitted values were compared to those calculated directly by the finite element method (FEM). Finally, a checking and clinical validation of the statistical study were made, by studying two cases of real patients. The vertical displacements and principal stress distribution obtained for the specific tracheal model were in agreement with those calculated by FE simulations with a maximum absolute error of 1.2 mm and 0.17 MPa, respectively. It was concluded that the resulting decision support tool provides a fast, accurate and simple tool for the thoracic surgeon to predict the stress state of the trachea and the reduction in the ability to swallow after implantation. Thus, it will help them in taking decisions during pre-operative planning of tracheal interventions.     

Ab initio and molecular dynamics studies of solid β-HMX: effects of hydrostatic pressure and high temperature

Using first-principles density functional theory and classical molecular dynamics (MD), the structural, electronic and mechanical properties of the energetic material β-HMX have been studied. The crystal structure optimised by the local density approximation calculations compares reasonably with the experimental data. Electronic band structure and density of states indicate that β-HMX is an insulator with a band gap of 3.059 eV. The pressure effect on the crystal structure and physical properties has been investigated in the range of 0–40 GPa. The crystal structure and electronic properties change slightly as the pressure increases from 0 to 2.5 GPa; when the pressure is above 2.5 GPa, further increment of the pressure results in significant changes in crystal structure. There is a larger compression along the b-axis than along the a- and c-axes. Isothermal–isobaric MD simulations on β-HMX were performed in the temperature range of 5–400 K. Phase transition at 360 K, corresponding to a volume interrupt, was found. The computed thermal expansion coefficients show anisotropic behaviour with a slightly larger expansion along the b- and c-axes than along the a-axis. In the temperature range of 5–360 K, β-HMX possesses good plasticity and its stiffness decreases with increasing the temperature.     

Influence of ventrolateral surface of medulla on reflex tracheal constriction

To assess the role of structures located superficially near the ventrolateral surface of the medulla on the reflex constriction of tracheal smooth muscle that occurs when airway and pulmonary receptors are stimulated mechanically or chemically, experiments were conducted in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats. Pressure changes within a bypassed segment of the trachea were used as an index of alterations smooth muscle tone. The effects of focal cooling of the intermediate areas or topically applied lidocaine on the ventral surface of the medulla on the response of the trachea to mechanical and chemical stimulation of airway receptors were examined. Atropine abolished tracheal constriction induced by mechanical stimulation of the carina or aerosolized histamine, showing that the responses were mediated over vagal pathways. Moderate cooling of the intermediate area (20 degrees C) or local application of lidocaine significantly decreased the tracheal constrictive response to mechanical activation of airway receptors. Furthermore, when the trachea was constricted by histamine, cooling of the intermediate area significantly diminished the increased tracheal tone, whereas rewarming restored tracheal tone to the previous level. These findings suggest that under the conditions of the experiments the ventral surface of the medulla plays an important role in constriction of the trachea by inputs from intrapulmonary receptors and in the modulation of parasympathetic outflow to airway smooth muscle.     

Histamine-induced changes in rat tracheal goblet cell mucin store and mucosal edema

The pathology of chronic asthma in human and mouse is characterized by inflammation and remodeling of airway tissues. As a result of repeated inflammatory insults to the lower airways, smooth muscle thickening, mucin secretion and airway hyperreactivity may develop. In ovalbumin (OVA)-sensitized mice with repeated challenges with OVA to the lower airways, the trachea and bronchi are characterized by goblet cell hyperplasia and mucus hypersecretion from goblet cells. Previous study reports that intravenous (i.v.) application of a high dose of capsaicin releases tachykinin from capsaicin-sensitive nerves, producing acute plasma leakage and mucosal edema formation and causing depletion of mucin granules in goblet cells that results in a reduction in the number and size of Alcian blue (AB)-positive goblet cells in the rat trachea within a few minute after capsaicin application. Histamine is an important non-neural mediator of asthma from mast cells. The present study investigated whether i.v. application of a high dose of histamine (18 μmol/ml/kg) could result in these acute changes and the similar time-course changes in rat trachea. The tracheal whole mounts stained with chloroacetate esterase reagent and AB and tracheal methacrylate sections stained with AB and periodic acid-Schiff reagent were used for evaluation of histological and cellular changes. At 5 min after histamine application, mucosal leaky venules were numerous and subepithelial edema ratio (% of length of edema along the mucosal epithelial circumference of tracheal cross section) was found to be 48.2 ± 4.9, which was greater (P < 0.01) than saline-treated rats. But, the number of AB-positive goblet cells, 2,030 ± 170/mm² of mucosal surface epithelium, was similar to saline-treated group (P > 0.05). One day later, edema ratio remained large and the number of AB-positive goblet cells was 1,140 ± 150/mm² epithelium, reduced to half the number of the group at 5 min after histamine (P < 0.01). It is suggested that mucus hypersecretion occurred at this time point. At 3 or 5 days after histamine, edema ratio gradually decreased. The number of AB-positive goblet cells continued to remain small on day 3. On day 5 after histamine, the number of AB-positive goblet cells restored to the level of rat group at 5 min after histamine application. At 7 days after histamine, edema ratio returned to the level of saline-treated group. It is concluded that degranulation and thinning of tracheal goblet cells and mucus hypersecretion lagged behind histamine-induced acute plasma leakage and edema, and restoration of mucin store in goblet cells was associated with remission of mucosal edema.     

Anisotropic material behaviours of soft tissues in human trachea: an experimental study

BackgroundHuman trachea is a multi-component structure composed of cartilage, trachealis muscle, mucosa and submucosa membrane and adventitial membrane. Its mechanical properties are essential for an accurate prediction of tracheal deformation, which has a significant clinic relevance. Efforts have been made in quantifying the material behaviour of tracheal cartilage and trachealis muscle. However, the material behaviours of other components have been least investigated.MethodsThree human cadaveric trachea specimens were used in this study. Trachealis muscle, mucosa and submucosa membrane and adventitia membrane were excised to perform the uniaxial test in axial and circumferential directions. In total, 72 tissue strips were prepared and tested. Tangent modulus was used to quantified the stiffness of each tissue strip at various stretch levels.ResultsThe obtained results indicated that all types of tracheal soft tissues were highly non-linear and anisotropic. Trachealis muscle in the circumferential direction had the most excellent extensibility; and the adventitial collagen membrane in the circumferential direction was the stiffest.ConclusionThis study is helpful in understanding the material behaviour of trachea. Obtained results can be used for computational and analytic modelling to quantify the tracheal deformation.     

Release of prostaglandin-like material from isolated cat tracheal muscle by electrical and mechanical stimulation.

Release of PGE-like material has been studied on the isolated continuously-superfused cat tracheal muscle using dynamic bioassay methods. The effluent of transmural electrically-stimulated cat tracheal muscle induced a contraction when superfused over the rat stomach fundus strip. This response did not alter with atropine, methysergide, phentolamine and propranolol but was inhibited by aspirin and Sc 19220. The same myotropic activity in the effluent was found when trachea was mechanically stimulated by an additional increase in tension. The effluent from mechanically- and electrically-stimulated tracheal muscle caused a definite relaxation when superfused over a second cat tracheal muscle contracted by serotonin and pretreated with propranolol. Electrically-stimulated cat trachea itself gave a relaxant response which was blocked by propranolol but potentiated by aspirin. From these results it was concluded that both electrical and mechanical stimulation can elicit a release of PGE-like material from isolated cat tracheal muscle.     

Biomechanical properties of the pelvic floor muscles of continent and incontinent women using an inverse finite element analysis

Pelvic disorders can be associated with changes in the biomechanical properties in the muscle, ligaments and/or connective tissue form fascia and ligaments. In this sense, the study of their mechanical behavior is important to understand the structure and function of these biological soft tissues. The aim of this study was to establish the biomechanical properties of the pelvic floor muscles of continent and incontinent women, using an inverse finite element analysis (FEA). The numerical models, including the pubovisceral muscle and pelvic bones were built from magnetic resonance (MR) images acquired at rest. The numerical simulation of Valsalva maneuver was based on the finite element method and the material constants were determined for different constitutive models (Neo-Hookean, Mooney-Rivlin and Yeoh) using an iterative process. The material constants (MPa) for Neo-Hookean (c₁) were 0.039 ± 0.022 and 0.024 ± 0.004 for continent vs. incontinent women. For Mooney-Rivlin (c₁) the values obtained were 0.026 ± 0.010 vs. 0.016 ± 0.003, and for Yeoh (c₁) the values obtained were 0.031 ± 0.023 vs. 0.016 ± 0.002, (p < 0.05). Muscle displacements obtained in the numerical simulations of Valsalva maneuver were compared with the muscle displacements obtained through additional dynamic MRI. Incontinent women presented a higher antero-posterior displacement than the continent women. The results were also similar between MRI and numerical simulations (40.27% vs. 42.17% for Neo-Hookean, 39.87% for Mooney-Rivlin and 41.61% for Yeoh). Using an inverse FEA coupled with MR images allowed to obtain the in vivo biomechanical properties of the pelvic floor muscles, leading to a relationship between them for the continent and incontinent women in a non-invasive manner.     

Reflex changes in tracheal smooth muscle tone during high-frequency oscillation

We examined the effect of high-frequency oscillatory ventilation (HFOV) on tracheal smooth muscle tension and upper airway resistance in anesthetized dogs. The animals were ventilated via a low tracheostomy by HFOV or conventional intermittent positive pressure ventilation (IPPV) with and without added positive end-expiratory pressure (PEEP). The transverse muscle tension of the trachea above the tracheostomy was measured and found to be lower during HFOV when compared with IPPV or IPPV with PEEP. When both vagi were cooled to 8 degrees C to interrupt afferent traffic from the lungs, there was no longer any difference between the modes of ventilation. In a second series of experiments, the airflow resistance of the upper airway above the tracheostomy was measured (Ruaw). During HFOV, Ruaw was significantly lower than during either IPPV or IPPV with PEEP. We conclude that HFOV induces a relaxation of tracheal smooth muscle and a reduction of upper airway resistance through a vagally mediated mechanism.     

Numerical investigation of inspiratory airflow in a realistic model of the human tracheobronchial airways and a comparison with experimental results

In this article, the results of numerical simulations using computational fluid dynamics (CFD) and a comparison with experiments performed with phase Doppler anemometry are presented. The simulations and experiments were conducted in a realistic model of the human airways, which comprised the throat, trachea and tracheobronchial tree up to the fourth generation. A full inspiration/expiration breathing cycle was used with tidal volumes 0.5 and 1 L, which correspond to a sedentary regime and deep breath, respectively. The length of the entire breathing cycle was 4 s, with inspiration and expiration each lasting 2 s. As a boundary condition for the CFD simulations, experimentally obtained flow rate distribution in 10 terminal airways was used with zero pressure resistance at the throat inlet. CCM+ CFD code (Adapco) was used with an SST k-\(\upomega \) low-Reynolds Number RANS model. The total number of polyhedral control volumes was 2.6 million with a time step of 0.001 s. Comparisons were made at several points in eight cross sections selected according to experiments in the trachea and the left and right bronchi. The results agree well with experiments involving the oscillation (temporal relocation) of flow structures in the majority of the cross sections and individual local positions. Velocity field simulation in several cross sections shows a very unstable flow field, which originates in the tracheal laryngeal jet and propagates far downstream with the formation of separation zones in both left and right airways. The RANS simulation agrees with the experiments in almost all the cross sections and shows unstable local flow structures and a quantitatively acceptable solution for the time-averaged flow field.     

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart failure. Here, we describe a detailed surgical procedure for creating pressure overload and cardiac hypertrophy in rats by constriction of the ascending aorta using a small metallic clip. After anesthesia, the trachea is intubated by inserting a cannula through a half way incision made between two cartilage rings of trachea. Then a skin incision is made at the level of the second intercostal space on the left chest wall and muscle layers are cleared to locate the ascending portion of aorta. The ascending aorta is constricted to 50–60% of its original diameter by application of a small sized titanium clip. Following aortic constriction, the second and third ribs are approximated with prolene sutures. The tracheal cannula is removed once spontaneous breathing was re-established. The animal is allowed to recover on the heating pad by gradually lowering anesthesia. The intensity of pressure overload created by constriction of the ascending aorta is determined by recording the pressure gradient using trans-thoracic two dimensional Doppler-echocardiography. Overall this protocol is useful to study the remodeling events and contractile properties of the heart during the gradual onset and progression from compensated cardiac hypertrophy to heart failure stage.     

The effects of methylxanthines, ethymizol, ephedrine and papaverine on guinea pig and dog trachea

The study was aimed to compare the effects of pentoxyphylline, aminophylline, choline theophyllinate and ethymizol on guinea pig and dog trachea with those of theophylline, papaverine and ephedrine. The effects of these drugs on the basal tension, on dose-response curves for muscle contraction produced by histamine and on cAMP level were investigated in guinea pig trachea, together with their influence on the resting and histamine-evoked mechanical and membrane activities of dog trachea. Like papaverine, pentoxyphylline did not alter the resting membrane potential, although it relaxed both tracheal preparations, and it antagonised the effects histamine and raised the cAMP level of the smooth muscle. The effects of ethymizol were similar to those of theophylline and its water soluble derivatives (aminophylline and choline theophyllinate). Whereas, ephedrine although it decreased the basal tension and inhibited histamine-evoked responses, also elicited substantial hyperpolarization of the smooth muscle membrane with no effect on the cAMP level. These findings are consistent with the hypothesis that cAMP has an important role in the action of some bronchodilator drugs; however, it is concluded that the possibility of contributing of their action on membrane potential to their action needs to be considered. The similarity of the potencies of ethymizol and pentoxyphylline to that of classical bronchodilators in inhibiting contraction of guinea pig and dog tracheal smooth muscle suggests that they may have a therapeutic value.     

The Recovery Process of Mice Tracheal Epithelium Injured by 5-FU and Its Microarray Analysis

Although the research on the localization of trachea stem cells has made a rapid progress, the mechanism of proliferation and differentiation of trachea stem cells remains unclear. The objective of this study is to observe and analyze the recovery process of mice tracheal epithelium injured by 5-FU, and to investigate the mechanism involved in the regulation of tracheal stem cells proliferation and differentiation through morphological, immunofluorescence, and microarray analysis. After treatment with 5-FU, the mature cells were dead and desquamated. Only a few G₀ phase cells remained on the basement membrane. When supplied with normal culture media, the cells eventually became flat, cubic, and restored as pseudostratified epithelium. These G₀ phase cells were ABCG2 positive. It suggested that these cells could differentiate into cilia cells or Clara cells, and had the multi-differentiation ability of stem cells. We examinated the expression profile of genes involved in the stem cell differentiation in normal tracheal epithelial cells and the regenerated epithelial cells at 24 and 48 h after injured by 5-FU using gene microarray. After 24 h treatment, 8 genes were up-regulated and 31 genes were down-regulated. After 48 h treatment, 5 genes were up-regulated and 42 genes were down-regulated. The differential gene expressions in gene microarray analysis focused on cell cycle regulation, intercellular junction, fibroblast growth factors, bone morphogenetic protein, Notch and Wnt-signaling pathways, which suggested that the differential gene expressions might be closely associated with the proliferation and differentiation of tracheal stem cells.     

Study on cartilaginous and muscular strains of rat trachea

This paper introduces a new method, termed Twice Cutting, for obtaining the zero-stress states of cartilage and muscle of trachea. The method applied cuts at the two junctions of tracheal cartilage and muscle perpendicular to the tangent lines of cartilage at its tips. The cartilaginous and muscular opening angles are defined for the first time in Twice Cutting methods. Based on the analysis of cartilaginous and muscular geometric information in no-load and zero-stress states, it is found that there are compressive and tensile residual strains in the inner and outer walls of the cartilage respectively. Residual strains at the muscular inner wall of tracheal rings near bifurcation are negative, whereas those of other rings are positive, and residual strains at outer wall of all rings are positive. This phenomenon of tracheal muscle residual strains is different from those of vessel etc. The results also show that the absolute values of cartilaginous strains are considerably smaller than that of muscular ones, with the ratio being around 0.05. The values of all the tracheal parameters, including residual strains and opening angles, are reducing with the increasing value of tracheal rings’ position. So the consequences obtained in this paper not only indicate that the trachea is a non-uniform tissue along the circumferential and axial directions, but also reveal the differences between the trachea and other living tissues, such as vessel, esophagus. This is a basic research for further work, such as determining stress in trachea, to which the cartilaginous and muscular zero-stress states should be referred.     

In vitro isolation and cultivation of rabbit tracheal epithelial cells using tissue explant technique

Epithelial cells from tracheal mucosa offer significant potential as a cell source in development of tissue-engineered trachea. The purpose of this study was to investigate and optimize a suitable culture system for tracheal epithelial cells, including the methods of primary culture, passage, identification, and cryopreservation. Epithelial cells were isolated from rabbit tracheal mucosa using tissue explant technique and were subjected to immunohistochemistry, immunofluorescence, and cryopreservation after purification. Epithelial cells reached confluency at 14–15 d. Immunohistochemical staining for cytokeratin showed brown yellow-positive cytoplasm and blue-counterstained nuclei, while immunofluorescence staining for cytokeratin showed green-positive cytoplasm and clear cell outline, indicating that the cultured cells had properties of epithelial cells. After recovery, epithelial cells exhibited high survival and viability. The results demonstrated that in vitro isolation and cultivation model was successfully established to provide high proliferative capacity, typical morphology and characteristics of tracheal epithelial cells from trachea mucosa by the use of the tissue explant technique.     

Mechanical Loading by Fluid Shear Stress of Myotube Glycocalyx Stimulates Growth Factor Expression and Nitric Oxide Production

Skeletal muscle fibers have the ability to increase their size in response to a mechanical overload. Finite element modeling data suggest that mechanically loaded muscles in vivo may experience not only tensile strain but also shear stress. However, whether shear stress affects biological pathways involved in muscle fiber size adaptation in response to mechanical loading is unknown. Therefore, our aim was twofold: (1) to determine whether shear stress affects growth factor expression and nitric oxide (NO) production by myotubes, and (2) to explore the mechanism by which shear stress may affect myotubes in vitro. C2C12 myotubes were subjected to a laminar pulsating fluid flow (PFF; mean shear stress 0.4, 0.7 or 1.4 Pa, 1 Hz) or subjected to uni-axial cyclic strain (CS; 15 % strain, 1 Hz) for 1 h. NO production during 1-h PFF or CS treatment was quantified using Griess reagent. The glycocalyx was degraded using hyaluronidase, and stretch-activated ion channels (SACs) were blocked using GdCl₃. Gene expression was analyzed immediately after 1-h PFF (1.4 Pa, 1 Hz) and at 6 h post-PFF treatment. PFF increased IGF-I Ea, MGF, VEGF, IL-6, and COX-2 mRNA, but decreased myostatin mRNA expression. Shear stress enhanced NO production in a dose-dependent manner, while CS induced no quantifiable increase in NO production. Glycocalyx degradation and blocking of SACs ablated the shear stress-stimulated NO production. In conclusion, shear stress activates signaling pathways involved in muscle fiber size adaptation in myotubes, likely via membrane-bound mechanoreceptors. These results suggest that shear stress exerted on myofiber extracellular matrix plays an important role in mechanotransduction in muscle.     

Effects of sitting postures on risks for deep tissue injury in the residuum of a transtibial prosthetic-user: a biomechanical case study

Transtibial amputation prosthetic-users are at risk of developing deep tissue injury (DTI) while donning their prosthesis for prolonged periods; however, no study addresses the mechanical loading of the residuum during sitting with a prosthesis. We combined MRI-based 3D finite element modelling of a residuum with an injury threshold and a muscle damage law to study risks for DTI in one sitting subject in two postures: 30°-knee-flexion vs. 90°-knee-flexion. We recorded skin-socket pressures, used as model boundary conditions. During the 90°-knee-flexion simulations, major internal muscle injuries were predicted (>1000 mm³). In contrast, the 30°-knee-flexion simulations only produced minor injury ( < 14 mm³). Predicted injury rates at 90°-knee-flexion were over one order of magnitude higher than those at 30°-knee-flexion. We concluded that in this particular subject, prolonged 90°-knee-flexion sitting theoretically endangers muscle viability in the residuum. By expanding the studies to large subject groups, this research approach can support development of guidelines for DTI prevention in prosthetic-users.     

Study on cartilaginous and muscular strains of rat trachea

Han and Fung (1991)[1] studied the zero-stressstates of porcine and canine tracheas by cutting themidpoints of cartilage and muscle respectively. Themethod of Fung, termed Once Cutting method in thispaper, was also used by Liu, Wang and Teng (2002)[2]in studying residual strain of rat tracheas. They all re-ported that the no-load state of trachea is not itszero-stress state, but the residual stress (strain) existsin no-load tracheal ring. The tracheal ring would openup into a figure of “C…     

Functional anatomy of the vagal innervation of the cervical trachea of the dog.

The canine cervical trachea has been used for numerous studies regarding the neural control of tracheal smooth muscle. The purpose of the present study was to determine whether there is lateral dominance by either the left or right vagal innervation of the canine cervical trachea. In anesthetized dogs, pressure in the cuff of the endotracheal tube was used as an index of smooth muscle tone in the trachea. After establishment of tracheal tone, as indicated by increased cuff pressure, either the right or left vagus nerve was sectioned followed by section of the contralateral vagus. Sectioning the right vagus first resulted in total loss of tone in the cervical trachea, whereas sectioning the left vagus first produced either a partial or no decrease in tracheal tone. After bilateral section of the vagi, cuff pressure was recorded during electrical stimulation of the rostral end of the right or left vagus. At the maximum current strength used, stimulation of the left vagus produced tracheal constriction that averaged 28.5% of the response to stimulation of the right vagus (9.0 +/- 1.8 and 31.6 +/- 2.5 mmHg, respectively). In conclusion, the musculature of cervical trachea in the dog appears to be predominantly controlled by vagal efferents in the right vagus nerve.     

Intrinsic innervation in the tracheal smooth muscle of the large flying fox (Pteropus vampyrus): an immunohistochemical study

Structure and innervation of the trachea of the large flying fox (Pteropus vampyrus) were examined by mean hematoxylin-eosin staining and immunohistochemical methods. The tracheal rings were predominantly comprised of bone with a small amount of hyaline cartilage. Bone contained bone marrow and hyaline cartilage attached at the ends of the tracheal rings. The tracheal rings in the anterior third of the trachea were connected at each end with connective tissue to almost form a ring. A narrow membranous wall comprising a single layer of smooth muscle was present in the middle third, while inner and outer layers of smooth muscle were present in the posterior third. Protein gene product 9.5 (PGP 9.5)-, nitric oxide synthase (NOS)-, galanin- and vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers were present in the epithelium, lamina propria, smooth muscle layer and tunica adventitia. In the tunica adventitia, many PGP 9.5- and NOS-immunoreactive neurons were found singly or in small ganglia, while some VIP- and galanin-immunoreactive neurons were observed. A few PGP 9.5- and NOS-immunoreactive neurons were found in the submucosal layer. These results suggest that the trachea of the large flying fox has a rigid structure of tracheal rings and that the posterior two-thirds of the trachea probably contract via the actions of smooth muscles innervated with peptidergic or nitrenergic neurons that are located in tracheal ganglia, whereas the anterior third is non-mobile.     

Absence of nonadrenergic noncholinergic relaxation in the cat cervical trachea

Published in vivo experiments have not supported in vitro reports of the presence of nonadrenergic noncholinergic (NANC) inhibitory pathways in the cat trachea. We therefore examined these pathways, measuring tension in an innervated tracheal segment, flow resistance in more distal airways, and dynamic compliance, in 10 anesthetized mechanically ventilated cats. Initially, cervical vagal stimulation evoked contraction followed by relaxation of smooth muscle of trachea and lower airways; sympathetic stimulation evoked relaxation only. After muscarinic blockade and restoration of smooth muscle tone with 5-hydroxytryptamine (5-HT) applied topically to the tracheal mucosa, vagal stimulation did not affect tracheal segment tension, whereas sympathetic-evoked relaxation was preserved. Similar results were found when tone was restored with intravenous 5-HT, with vagal stimulation also decreasing resistance and increasing compliance. We conclude that NANC pathways are present in lower airways but not in the cervical trachea of the cat. We hypothesize that parasympathetic constriction of cat airway smooth muscle can occur without simultaneous NANC activation, whereas NANC activity occurs only in tandem with parasympathetic stimulation.