Blood supply of the trachea and bronchi in the rat

Existence of longitudinal and circular arterio-arterial anastomoses are stated, as well as various ways of outflow from the veins of the organs studied; this demonstrates essential compensatory abilities of this bed in blood supply regulation and draining at inflow and outflow from the microcirculatory system bed. Different topography of the arterial sources, venous plexuses, capillary fields allows to suppose different histophysiology of the tracheal zones mentioned: the anterior (laryngotracheal), middle and posterior (bifurcational). For the tracheal microcirculatory bed, metamerically repeated microcirculatory areas are peculiar. Distribution of the bronchial arteries takes place up to the terminal bronchi. In the area of the latter, anastomoses of the bronchial vessels with the pulmonary artery are observed.     

Effects of triazolopyrimidine on lipid peroxidation and nitric oxide levels in the corticosteroid-impaired healing of rat tracheal anastomoses

Corticosteroids are used to reduce the oedema and prevent scar tissue formation of the upper airways by their ability to inhibit influx of inflammatory cells, limit capillary permeability and block collagen synthesis in the early stages of wound healing. Triazolopyrimidine (Trapidil) is an antiplatelet agent that acts in part as a phosphodiesterase inhibitor and as a competitive inhibitor of the platelet-derived growth factor (PDGF) receptor. Trapidil, with its vasodilator and NO releasing effect may have some potential to diminish the tissue injury. This study was carried out to evaluate the effects of trapidil (triazolopyrimidine) on lipid peroxidation and nitric oxide in the corticosteroid-impaired healing of tracheal anastomoses. Thirty-four adult Wistar rats were divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: group I, control, (GI, n = 6); group II, sham, (GII, n = 6); group III, dexamethasone, 0.1 mg kg(-1) twice daily intramuscularly, (GIII, n = 8); group IV, trapidil, 6 mg kg(-1) twice daily intraperitoneally (GIV, n = 7); group V, dexamethasone, 0.1 mg kg(-1) plus trapidil, 6 mg kg(-1) twice daily (GV, n = 7), for 1 week. After 1 week, anastomotic healing was assessed by measurement of bursting pressure, evaluation of histopathology, measurement of MDA and nitrite/nitrate levels. In GIII, GIV and GV bursting pressures resulted in significantly reduced anastomotic strength compared to the controls (p < 0.001 for all groups). The difference between bursting pressures of GIII and GIV was not found to be statistically significant (p = 0.966). In regard to fibroblast proliferation and collagen content, a significant difference was found between GIII and GI (p < 0.01), A significant difference was also found when GIV and GV were compared to GIII (p < 0.01). MDA and nitrite/nitrate levels were found to be higher in GIII when compared to all other groups. MDA levels of GIV and GV rats were found to be lower than GIII (p < 0.001, for both groups). The nitrite/nitrate levels of GIV and GV rats were found to be lower than GIII (p < 0.05), and higher than GI (p < 0.001). Trapidil may be useful for its preventive effects on lipid peroxidation and possible increases in NO in cases with corticosteroid-impaired healing of trachea anastomoses.     

Occurrence of anastomoses of the intrahepatic bile ducts

Eighty-four human livers were investigated with regard to the existence of vascular communications within their biliary tracts. Even with the help of a most subtle technique we could not detect any junctions between the bile ducts, so that there is no evidence of primary anastomoses between the main lobes, between the segments, or inside the segments. In case of chronic biliary obstruction only the major ducts, e.g., up to the fourth generation, are amplified. There is an inflammatory reaction around the smaller vessels, followed by fibrosis and shrinking of the connective tissue. That is why the formation of secondary anastomoses cannot happen under pathological conditions.     

Comparative morphology of tissues when using polypropylene and polytetrafluoretilen prostheses

The synthetic mesh is widely used for treatment of hernias. We conducted a comparative study of the morphological pattern of inflammation, the cellular composition of tissues and dynamics of scar formation in mice when using implants "Esfil" and "Unifleks" under influence of single and double injection of cultured fibroblast and without such injection to the region of stents location. A more pronounced inflammatory reaction during the study period of investigation was observed in the case of "Esfil". In the late period of the study, a higher percentage of fibroblasts was observed in the case of the prosthesis "Unifleks" compared to the prosthesis "Esfil". Injection of cultured fibroblasts modifies the curve of the dynamics of the inflammatory process by making it smoother in the case of both prostheses. So, more preferred is the use of prostheses "Unifleks".     

Experimental microvascular polytetrafluoroethylene grafts: 6-month patency

The efficacy of 1-mm internal-diameter polytetrafluoroethylene as a microvascular prosthesis is unclear. In this study, 8-mm-long segments of this material were implanted into the femoral arteries of 30 rats. Animals were examined every 2 weeks up to 6 months by Doppler ultrasound. Cumulative patency by the life-table method was 86.7 percent at 6 months. There were 26 patent grafts, 2 occlusions, and 2 deaths. Intimal hyperplasia adjacent to the anastomoses was seen in the native arteries. The pseudointima lining the grafts was cellular near the anastomoses but usually acellular in midgraft regions. It is concluded that if early failure does not occur, then good long-term patency is possible with 1-mm polytetrafluoroethylene in this setting and that patency is not dependent on development of a cellular pseudointima. Longer graft segments should be evaluated in future studies.     

FSI analysis of a human trachea before and after prosthesis implantation

In this work we analyzed the response of a stenotic trachea after a stent implantation. An endotracheal stent is the common treatment for tracheal diseases such as stenosis, chronic cough, or dispnoea episodes. Medical treatment and surgical techniques are still challenging due to the difficulties in overcoming potential complications after prosthesis implantation. A finite element model of a diseased and stented trachea was developed starting from a patient specific computerized tomography (CT) scan. The tracheal wall was modeled as a fiber reinforced hyperelastic material in which we modeled the anisotropy due to the orientation of the collagen fibers. Deformations of the tracheal cartilage rings and of the muscular membrane, as well as the maximum principal stresses, are analyzed using a fluid solid interaction (FSI) approach. For this reason, as boundary conditions, impedance-based pressure waveforms were computed modeling the nonreconstructed vessels as a binary fractal network. The results showed that the presence of the stent prevents tracheal muscle deflections and indicated a local recirculatory flow on the stent top surface which may play a role in the process of mucous accumulation. The present work gives new insight into clinical procedures, predicting their mechanical consequences. This tool could be used in the future as preoperative planning software to help the thoracic surgeons in deciding the optimal prosthesis type as well as its size and positioning.     

Mast cell-derived TNF-alpha primes sensory nerve endings in a pulmonary hypersensitivity reaction

TNF-alpha is a cytokine associated with inflammatory diseases, including asthma. Increased levels of TNF-alpha were found in the bronchoalveolar lavage fluid of mice undergoing a dinitrofluorobenzene (DNFB)-induced non-IgE-mediated pulmonary hypersensitivity reaction. We report in this work that TNF-alpha increases the susceptibility of sensory neurons to dinitrobenzene sulfonic acid (DNS) and capsaicin, leading to a tracheal vascular hyperpermeability response in DNFB-sensitized and DNS-challenged mice. mAb against TNF-alpha or the TNFR1 inhibited this hyperpermeability response in DNFB-sensitized and DNS-challenged mice. Furthermore, the hyperpermeability response after DNS challenge was abolished in DNFB-sensitized mast cell-deficient WBB6F(1)-W/W(V) mice. These animals showed a remarked decrease of TNF-alpha bronchoalveolar lavage fluid levels after a single DNS challenge. The hyperpermeability response after DNS challenge was regained in mast cell-deficient mice after mast cell reconstitution. These findings indicate a prominent role for TNF-alpha and its TNFR1 in the DNFB-induced tracheal hyperpermeability response. We propose that a priming effect of mast cell-derived TNF-alpha on the sensory neurons could be the mechanism of action of TNF-alpha in the vascular hyperpermeability response in tracheas of mice undergoing a pulmonary hypersensitivity reaction.     

Testing of a new prototype surgical stapler that automates the rollover sleeve technique for venous anastomoses

The creation of successful vascular anastomoses is of primary importance in many surgical fields. Numerous attempts to automate this process have been made. These techniques have slowly gained acceptance, but their use is still limited. This report details feasibility testing of a new prototype stapler that automates the rollover sleeve technique for venous vascular anastomoses. Male and female mongrel dogs (n=7) (25-32 kg) were used. A segment of the right (n=5) or left (n=2) iliac vein was harvested for interposition grafts after the contra lateral side was transected. In each dog, two end-to-end venous anastomoses at the interposition grafts were performed. The standard anastomosis employed continuous mattress sutures. The experimental anastomosis was performed with a new prototype surgical stapler. The stapled anastomosis was proximal and the sutured was distal. In all experiments, it was possible to perform the experimental anastomosis with the stapler. Complications included two small leaks, one due to misfiring of a single pin in one experimental site. These leaks required suture reinforcement. One dog died of hemorrhage due to a slipped suture at the vein harvest site. One vein had thrombus seen at the sutured site although no technical abnormalities at either of the anastomoses could be found. After two weeks, grafts were inspected grossly and histologically. Healing appeared normal. There was a trend for less inflammatory cells infiltrating stapled sites; however, this was not statistically significant. The experiments demonstrate that this device can automate the rollover sleeve technique for venous anastomoses.     

Clinical utilization of mechanical sutures for intestinal anastomosis in Macaca mulatta.

Using three mechanical stapling instruments that employ stainless steel wire staples, a Mann-Bollman fistula was created on the terminal ileum in 27 rhesus monkeys (Macaca mulatta). Two functional end-to-end anastomoses were accomplished and an ileostium constructed. Staples of various sizes were used; it was found that pediatric-sized staples were necessary for the intestinal tissue of these primates. Six months after surgery, microscopic examination revealed encapsulation of the staples by granulomatous inflammatory tissue. When staples of the proper size were selected, mechanical suturing provided rapid and consistent anastomoses, and wound closures had less edema, inflammation and necrosis than with conventional suturing methods.     

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.     

Comparative tissue morphology in using prostheses from polypropylene and polytetrafluoretilen

To treat hernias, polymer net implants are widely used. We carried out a comparative study of the morphological picture of inflammation, cellular composition of tissues, and dynamics of scar formation in mice in using the implants Esfil and Uniflex under conditions of single and double introduction of cultivated fibroblasts and without fibroblasts in the area of disposition of the endoprostheses. A more expressed inflammatory reaction throughout the entire period of time was observed in implantation of the material Esfil. In using the material Uniflex, there was revealed a higher percent of fibroblasts than in using the Esfil prosthesis. Introduction of cultivated fibroblasts in using both materials modified the curve of dynamics of the inflammatory process by making it smoother. Use of the Uniflex endoprosthesis is preferable.     

Effects of dry air and subsequent humidification on tracheal mucous velocity in dogs.

The impairment of mucociliary transport by dry air breathing and the restoration of function with subsequent humidification of inspired air were investigated in anesthetized dogs. Tracheal mucous velocity was measured by a cinebronchofiberscopic technique. The breathing of dry air through an uncuffed endotracheal tube produced almost complete cessation of the flow of tracheal mucus after 3 h. Subsequent breathing of air at 38 degrees C with 100% relative humidity restored tracheal mucous velocity to control values by the end of and additional 3 h. Histologic examination of the trachea at the end of the 3-h dry air breathing period revealed focal areas of sloughing of the ciliated epithelium and submucosal inflammation. Although morphometry was not employed, the inflammatory changes appeared to have progressed during 3 h of breathing fully humidified air subsequent to the dry air breathing period. These findings were consistent with previous reports that the inflammatory response to injury of the tracheobronchial mucosa might be delayed and that the mucociliary transport system has a great deal of functional reserve. We found that an artificial heat and moisture exchanger placed on the proximal end of an endotracheal tube partially protects against the suppression of tracheal mucous velocity caused by dry air breathing.     

IRAK-4 in macrophages contributes to inflammatory osteolysis of wear particles around loosened hip implants

TLRs recognizing PAMPS play a role in local immunity and participate in implant-associated loosening. TLR-mediated signaling is primarily regulated by IL-1 receptor associated kinase-M (IRAK-M) negatively and IRAK-4 positively. Our previous studies have proved that wear particles promote endotoxin tolerance in macrophages by inducing IRAK-M. However, whether IRAK-4 is involved in inflammatory osteolysis of wear particles basically, and the specific mechanism of IRAK-4 around loosened hip implants, is still unclear. IRAK-4 was studied in the interface membranes from patients in vivo and in particle-stimulated macrophages to clarify its role. Also, IL-1β and TNF-α levels were measured after particle and LPS stimulation in macrophages with or without IRAK-4 silenced by siRNA. Our results showed that the interface membranes around aseptic and septic loosened prosthesis expressed more IRAK-4 compared with membranes from osteoarthritic patients. IRAK-4 in macrophages increased upon particle and LPS stimulation. In the former, IL-1β and TNF-α levels were lower compared with those of LPS stimulation, and IRAK-4 siRNA could suppress production of pro-inflammatory cytokines. These findings suggest that besides IRAK-M, IRAK-4 also plays an important role in the local inflammatory reaction and contributes to prosthesis loosening.     

Effects of antigen on tracheal circulation and smooth muscle in sheep of different ages

The effects of Ascaris suum antigen on tracheal circulation and tracheal smooth muscle tone were compared in two groups of sheep: the first group was 1 yr old (14 sheep) and the second 5 yr old (8 sheep). Cranial tracheal arteries of anesthetized and paralyzed sheep were perfused at constant flow with monitoring of perfusion pressure. Tracheal smooth muscle tone was assessed by measuring changes in the external diameter of the cranial trachea. Close-arterial injection of antigen (1-20 micrograms) in young sheep produced dose-dependent vasodilation (6.1-15.5% fall in perfusion pressure) and smooth muscle contraction (0.06-0.28 mm reduction in tracheal diam). In old sheep, antigen (1-20 micrograms) produced vasoconstriction (4.1-16.8%) but no smooth muscle response. The smooth muscle contraction in young sheep was blocked by mepyramine (2 mg/kg iv) suggesting mediation by release of histamine. The vasodilation in young sheep and the vasoconstriction in old sheep were reduced by indomethacin (5 mg/kg iv), and the residual response was further reduced by FPL 55712 (2 mg/kg iv), suggesting mediation by both cyclooxygenase products and leukotrienes. Thus antigen given in the tracheal vasculature releases a mixture of inflammatory mediators. This mixture of mediators or their actions on the tracheal vasculature and smooth muscle may depend on the age of the sheep.     

Simulation of swallowing dysfunction and mechanical ventilation after a Montgomery T-tube insertion

The Montgomery T-tube is used as a combined tracheal stent and airway after laryngotracheoplasty, to keep the lumen open and prevent mucosal laceration from scarring. It is valuable in the management of upper and mid-tracheal lesions, while invaluable in long and multisegmental stenting lesions. Numerical simulations based on real-patient-tracheal geometry, experimental tissue characterization, and previous numerical estimation of the physiological swallowing force are performed to estimate the consequences of Montgomery T-tube implantation on swallowing and assisted ventilation: structural analysis of swallowing is performed to evaluate patient swallowing capacity, and computational fluid dynamics simulation is carried out to analyze related mechanical ventilation. With an inserted Montgomery T-tube, vertical displacement (Z-axis) reaches 8.01 mm, whereas in the Y-axis, it reaches 6.63 mm. The maximal principal stress obtained during swallowing was 1.6 MPa surrounding the hole and in the upper contact with the tracheal wall. Fluid flow simulation of the mechanical ventilation revealed positive pressure for both inhalation and exhalation, being higher for inspiration. The muscular deflections, considerable during normal breathing, are nonphysiological, and this aspect results in a constant overload of the tracheal muscle. During swallowing, the trachea ascends producing a nonhomogeneous elongation. This movement can be compromised when prosthesis is inserted, which explains the high incidence of glottis close inefficiency. Fluid simulations showed that nonphysiological pressure is established inside the trachea due to mechanical ventilation. This may lead to an overload of the tracheal muscle, explaining several related problems as muscle thinning or decrease in contractile function.     

PPARγ受体激动剂罗格列酮治疗的慢性阻塞性肺疾病样大鼠肺组织细胞因子的变化

目的研究过氧化物酶体增殖物激活的受体γ（PPARγ）激动剂罗格列酮对慢性阻塞性肺疾病（COPD）样大鼠肺组织、支气管肺泡灌洗液（BALF）中白介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）和白介素-4（IL-4）的影响。方法被动吸烟和气管内滴注脂多糖（LPS）复制大鼠模型并随机分为模型组和罗格列酮治疗组。制备肺组织匀浆和支气管肺泡灌洗液,用放免法检测IL-8、TNF-α,用ELISA法测IL-4。结果与模型组比较罗格列酮治疗组大鼠肺组织IL-8、TNF-α含量降低而IL-4含量增加。结论 PPAR-γ通路激活对COPD中的炎症反应有负调节作用。     

Flow pattern and shear stress distribution of distal end-to-side anastomoses. A comparison of the instantaneous velocity fields obtained by particle image velocimetry

OBJECTIVE: To describe the local hemodynamics and pressure losses of crural bypass anastomoses using instantaneous velocity fields acquired by particle image velocimetry (PIV). METHODS: Silastic models of a Taylor patch, a Miller cuff and a femoro-crural patch prosthesis (FCPP) were attached to a circuit driven by a Berlin Heart, providing a pulsatile flow with an amplitude of 450 to 25 ml/min (mean 200 ml/min). An outflow resistance of 0.5 mmHg/ml/min (peripheral resistance units, PRU) was modeled using small silastic tubes providing a phase shift of -12 degrees between flow and pressure curves. The working fluid consisted of a glycerine/water mixture with a viscosity of 4 mPas. Hollow glass spheres with a mean size of 9-13 microm were used as tracer particles. Instantaneous velocity fields were obtained by means of PIV and shear rates as well as shear stresses were calculated. Triggered by the flowmeter signal, 10 measurements at 100 ms intervals per cardiac cycle were obtained. The pressures were measured on the inflow and at both distal outflows. The resulting mean pressure losses due to flow separation and distal fluid acceleration were calculated. RESULTS: Inside the Taylor patch anastomosis a large flow separation at the hood containing a clockwise rotating vortex was found. Additionally a smaller flow separation at the heel and a flow stagnation zone on the floor of the recipient artery were observed. Conversely, inside the Miller cuff a counterclockwise rotating vortex was seen inside a large heel flow separation. The FCPP also showed typical separation areas at the hood and heel of the anastomosis, although these were smaller compared to the other anastomoses. Inside the FCPP anastomosis no vortex creation was observed throughout the cardiac cycle. The mainstream velocities at the inlet levels were comparable for the three anastomoses. A significant fluid acceleration was present at the antegrade as well as the retrograde outlets of the Taylor and Miller cuff, while the fluid acceleration at the antegrade outflow of the FCPP was small, which was attributed to the end-to-end configuration of the antegrade FCPP leg. The calculated normalized antegrade and retrograde pressure losses for the Taylor form were 0.90 and 0.88, for the Miller cuff 0.89 and 0.86 and for the FCPP 0.94 and 0.86, respectively. The shear stresses inside the flow separations of the three anastomoses were significantly lower than normal wall shear stresses. High shear stress levels were found inside the transition zones between flow separation and high velocity mainstream. CONCLUSIONS: The flow pattern inside cuffed or funnel shaped anastomoses consists of large flow separation zones, which are thought to be associated with intimal hyperplasia development. In addition, fluid accelerations at the distal outlets result in pressure losses, which may contribute to impaired crural perfusion.     

Free flaps to preserve below-knee amputation stumps: long-term evaluation

Five patients with insufficient soft-tissue coverage on below-knee amputation stumps have been treated with free-tissue transfer surgery to preserve a functional below-knee prosthetic level. The flaps employed include one latissimus dorsi myocutaneous flap, two latissimus dorsi muscle-skin graft flaps, one groin flap, and one foot-fillet flap. All five flaps survived; one patient required early venous anastomosis reexploration and revision. The patients have been followed for a mean duration of 5.5 years (range 3 to 8 years). The mean duration to first ambulation with a prosthesis was 3.6 months (range 2 to 7 months). Four of the five patients developed ulcerations on or adjacent to their flaps which required surgical revision. The patients required a mean of 1.28 prosthesis changes annually since surgery. The functional motion (mean active knee motion is 100 degrees) and ligamentous stability of the knee joints were well preserved in all patients. Five patients wear patella tendon-bearing prostheses, with one requiring an additional thigh corset. In two of the patients, nerve anastomoses to their flaps were performed. Both patients developed true cutaneous sensibility, but nevertheless experienced flap ulceration. All the patients are fully ambulatory on their free flaps. Free-tissue transfer can assist in preserving traumatic below-knee amputations so that patients can benefit from the functional advantage of a below-knee prosthetic device.     

Performance assessment of the Terry Fox jogging prosthesis for above-knee amputees

The Terry Fox jogging (TFJ) prosthesis was developed at Chedoke-McMaster Hospital to alleviate the asymmetric jogging pattern experienced by above-knee amputees when attempting to jog with conventional walking prostheses. This prosthesis features a spring-loaded, telescoping shank designed to eliminate any vaulting action and control the trunk motion during stance. The spring is intended to attenuate the impact forces and release its stored energy at push-off to provide momentum transfer to the jogger. This prosthesis was comprehensively assessed in the gait laboratory, by evaluating the kinematics, energy and power flow patterns of an above-knee amputee jogger wearing the TFJ prosthesis. Included in the assessment is the ability of the prosthesis to satisfy a set of relevant design criteria that have been established from non-amputee jogging patterns. An increased swing phase time for the prosthetic limb and the need to have the knee hyperextended throughout the stance phase contributed to an asymmetric jogging style. The telescoping action did lower the amputee's centre of mass, thereby reducing the vaulting effect. However, the spring only imparted a lifting action to the jogger and the ground reaction forces were double those of a non-amputee jogger. These findings clearly indicate a need to redesign the TFJ prosthesis and are being incorporated in the design of a new physiological jogging prosthesis.     

Effect of alignment changes on socket reaction moments during gait in transfemoral and knee-disarticulation prostheses: Case series

The alignment of a lower-limb prosthesis is critical to the successful prosthetic fitting and utilization by the wearer. Loads generated by the socket applied to the residual limb while walking are thought to be different in transfemoral and knee-disarticulation prostheses. The aim of this case series was to compare the socket reaction moments between transfemoral and knee-disarticulation prostheses and to investigate the effect of alignment changes on them. Two amputees, one with a transfemoral prosthesis and another with a knee-disarticulation prosthesis, participated in this study. A Smart Pyramid™ was used to measure socket reaction moments while walking under 9 selected alignment conditions; including nominally aligned, angle malalignments of 6° (flexion, extension, abduction and adduction) and translation malalignments of 15 mm (anterior, posterior, medial and lateral) of the socket relative to the foot. This study found that the pattern of the socket reaction moments was similar between transfemoral and knee-disarticulation prostheses. An extension moment in the sagittal plane and a varus moment in the coronal plane were dominant during stance under the nominally aligned condition. This study also demonstrated that alignment changes might have consistent effects on the socket reaction moments in transfemoral and knee-disarticulation prostheses. Extension and posterior translation of the socket resulted in increases in an extension moment, while abduction and lateral translation of the socket resulted in increases in a varus moment. The socket reaction moments may potentially serve as useful biomechanical parameters to evaluate alignment in transfemoral and knee-disarticulation prostheses.