Changes of minute ventilation in rabbits in experimental hyperthermia

The relative effect of the temperature on respiratory rhythm generation was studied in muscle-relaxed, artificially ventilated and bilaterally vagotomized rabbits under general anaesthesia (urethane and chloralose). Hypercapnia was produced during normothermia (38.8 +/- 0.6 degrees C) and hyperthermia (40.5 +/- 0.3 degrees C). The basic physiological parameters, efferent phrenic nerve activity and gasometric determinations in arterial blood were recorded. In the animals ventilated with a classic respirator hyperthermia produced a 118% increase of Veq value with a simultaneous 28% rise of the partial pressure of CO2. An increase of the stroke volume of the respirator during hyperthermia (in a degree sufficient for achieving PaCO2 value equal to the control value during normothermia) produced a 2% fall of Veq value due to an 8% fall in amplitude of the respiratory movements without changes of respiratory rate. Breathing in of a hypercapnic mixture caused a 131% rise of Veq above the control value in normothermia. This rise was due both to the increased respiratory rate and respiratory amplitude. During ventilation by means of a respirator controlled by phrenic nerve activity hyperthermia increased the electrophysiological equivalent of minute ventilation by 34%, with a 109% rise in the respiratory rate and with no change in PaCO2. Breathing of a hypercapnic mixture increased Veq without inducing any statistically significant changes in the respiratory rate and amplitude. The analysis of the results suggests that the effect of raised temperature on respiratory rhythm generation is manifested mainly as an impairment of the respiratory amplitude. Maintaining of minute ventilation proportional to the magnitude of respiratory drive is decisive in this phenomenon.     

Diaphragmatic activity and lung liquid flow in the unanesthetized fetal sheep.

For some time it has been suggested that breathing movements are made "in utero" and recently measurements of tracheal pressure and lung liquid flow in chronic fetal preparations have led to the hypothesis that rapid changes in these parameters are the result of respiratory muscle activity. To test this hypothesis diaphragmatic electrical activity was measured in seven chronic unanesthetized fetal sheep preparations and correlated with lung liquid flow and tracheal pressure. Diaphragmatic activity led to a fall of tracheal pressure and movement of a small volume of lung liquid into the lung. After the activity ceased, tracheal pressure returned to normal and flow diminished to zero or was directed out of the lung. The breathing pattern was unassociated with the net movement of lung liquid out of the lung. A histogram of the interval between breaths revealed a changing pattern of activity throughout gestation. The pattern was significantly altered after premature delivery of one animal with a respiratory problem. These observations provide evidence that respiratory muscles are active "in utero" and that the pattern of activity changes throughout gestation.     

经支气管镜气管插管与常规气管插管救治呼吸衰竭对比分析

目的：回顾性分析呼吸机辅助呼吸救治危重呼吸衰竭患者气管插管方式对于救治成功率的影响。方法：我科收治的各种呼吸衰竭患者94例,回顾分析插管方式对于救治成功率、引发心跳骤停及其对心肺复苏效果的影响。结果：经纤维支气管镜经口气管插管（35例）与经直接喉镜经口（59例）引发心跳骤停有明显统计学差异（X^2=11．5,v=1,t〈0．001）。经直接喉镜经口气管插管在术前用药与否对引发心跳骤停并无统计学意义,但是对于引发心跳骤停后心肺复苏成功率确有明显统计学意义。结论：经纤维支气管镜气管插管具有较高的安全性,在经直接喉镜气管插管是选择镇静药或浅麻醉药物应慎重,尽力避免心跳骤停和心肺复苏失败。     

A servo-controlled respiration system for inhalation studies in anesthetized animals

Rosenthal, Frank S., and Changhong Li. Aservo-controlled respiration system for inhalation studies inanesthetized animals. J. Appl.Physiol. 83(5): 1768-1774, 1997.To facilitate aerosol deposition experiments and aerosol exposures in anesthetized animals, a servo-controlled respiration system was developed and tested. The system induces ventilation by varying extrathoracic pressure in a whole body respirator in which an intubated animal isplaced. The pressure inside the whole body respirator is varied with athree-way servo-controlled spool valve connected to sources of positiveand negative pressure. A computer-based system detects respiratory flowand computes the controlling signal for the valve by using aproportional-integral-derivative algorithm, to achieve desired patternsof flow and volume vs. time. The system was used with dogs and found toaccurately induce various single-breath breathing patterns involvingconstant-flow inspirations and expirations as well as breath-holdperiods. A similar system was used to induced repeated breaths withdesired parameters for continuous exposure to particles and forventilation of animals between experiments.

     

TRACHEOTOMY IN BULBAR POLIOMYELITIS

Tracheotomy was performed on 181 of 351 patients with bulbar poliomyelitis. The essential indication for tracheotomy was secretional obstruction of the respiratory tract that could not be relieved by postural drainage and aspiration.Comparison of mortality rates in this series with those of previous series in which tracheotomy was not done in the presence of similar indications, suggests that the procedure may be life-saving in a considerable percentage of cases.Outside the respirator the tracheotomy can be done with or without the aid of the bronchoscope or endotracheal anesthesia tube. When done inside the opened respirator the Bennett flow-sensitive positive pressure machine should be used to supply oxygen to the patient while the respirator is not operating.     

Avoiding misdiagnosis in patients with dyspnea and wheezing: a case report illustrating the clinical implications of fixation error

Background

Bronchial asthma is a heterogeneous respiratory condition which can be mimicked by a wide range of pathologies including upper airways stenosis. The accurate diagnosis of asthma, as with other conditions, may be influenced by fixation errors, which are common in medicine and occur when a physician concentrates on only one element of a clinical case without considering other relevant aspects. Here we report a challenging case characterized by the contemporaneous presence of a common disease, asthma, together with a rare respiratory disease, idiopathic tracheal stenosis.

Case presentation

The 56-year-old female patient, a former smoker, was referred to our outpatient clinic for exertional dyspnea and persistent wheezing. There were no other respiratory or systemic symptoms over the past three months, and a psychological component was suspected. Spirometry with flow-volume evaluation and bronchoscopy were the key elements to establish the diagnoses and provide treatments. Once the diagnosis of asthma was confirmed, the combination of the anti-inflammatory corticosteroid fluticasone and the rapid-acting bronchodilator formoterol in a single inhaler effectively controlled the patient’s symptoms, confirming the favorable efficacy and safety profile which are reflected in the recommendations of the international guidelines.

Conclusions

In this paper we describe the clinical investigations and interventions that eventually confirmed a diagnosis of asthma complicated by an idiopathic tracheal stenosis and led to effective treatment of the patient. Awareness of fixation error may avoid misdiagnosis in patients with respiratory disease and a complicated history at presentation.

     

Cardiorespiratory failure in rat induced by severe inspiratory resistive loading.

The mechanisms underlying acute respiratory failure induced by respiratory loads are unclear. We hypothesized that, in contrast to a moderate inspiratory resistive load, a severe one would elicit central respiratory failure (decreased respiratory drive) before diaphragmatic injury and fatigue. We also wished to elucidate the factors that predict endurance time and peak tracheal pressure generation. Anesthetized rats breathed air against a severe load ( approximately 75% of the peak tracheal pressure generated during a 30-s occlusion) until pump failure (fall in tracheal pressure to half; mean 38 min). Hypercapnia and hypoxemia developed rapidly ( approximately 4 min), coincident with diaphragmatic fatigue (decreased ratio of transdiaphragmatic pressure to peak integrated phrenic activity) and the detection in blood of the fast isoform of skeletal troponin I (muscle injury). At approximately 23 min, respiratory frequency and then blood pressure fell, followed immediately by secondary diaphragmatic fatigue. Blood taken after termination of loading contained cardiac troponin T (myocardial injury). Contrary to our hypothesis, diaphragmatic fatigue and injury occurred early in loading before central failure, evident only as a change in the timing but not the drive component of the central respiratory pattern generator. Stepwise multiple regression analysis selected changes in mean arterial pressure and arterial Pco(2) during loading as the principal contributing factors in load endurance time, and changes in mean arterial pressure as the principal contributing factor in peak tracheal pressure generation. In conclusion, the temporal development of respiratory failure is not stereotyped but depends on load magnitude; moreover respiratory loads induce cardiorespiratory, not just respiratory, failure.     

Effects of changes in CO2 partial pressure on the sensation of respiratory drive

The purpose of this study was to determine whether a change in respiratory sensation accompanies an increase in CO2 partial pressure (PCO2) in the absence of any changes in the level and pattern of thoracic displacement and respiratory muscle force. Eleven normal subjects were artificially hyperventilated with a positive-pressure mechanical respirator. In separate trials the tidal volume (VT) was set at 10 and 18 ml/kg and the frequency of ventilation (f) was adjusted to maintain the base-line end-tidal PCO2 at approximately 30 Torr. Thereafter, at a constant controlled VT and f, the PCO2 was progressively increased by raising the inspired CO2 concentration. There were no changes in respiratory motor activity as determined from the peak inspiratory airway pressure (Paw) until the PCO2 reached 40.8 +/- 1.0 and 40.1 +/- 1.0 (SE) Torr in the large and small VT trials, respectively. Initially there was no conscious awareness of the change in respiratory activity. Subjects first signaled that ventilatory needs were not being satisfied only after a further increase in PCO2 to 44.7 +/- 1.3 and 42.3 +/- 1.0 (SE) Torr in the large and small VT trials and after the Paw had fallen to 55-60% of the base-line value. The results suggest that changes in respiratory sensation produced by increasing chemical drive are a consequence of increases in respiratory efferent activity, but a direct effect of changes in PCO2 on respiratory sensation cannot be excluded.     

USE OF THE ROCKING BED TO AUGMENT VENTILATION IN PATIENTS WITH POLIOMYELITIS

As the first step in an attempt to clarify criteria for use of the rocking bed rather than the respirator as an aid to breathing for patients with weakness of respiratory muscle function caused by poliomyelitis, ventilation studies were done on seven patients with pronounced weakness or paralysis of the respiratory muscles. Average tidal air volume was considerably less when the patient was on the rocking bed than when he was in the respirator. Since the tidal air volume with the patient on the rocking bed represents the maximum that can be produced with the apparatus, whereas the volume in the respirator represents the patient''s usual tidal air and the respirator is capable of a greater volume if necessary, it is apparent that in cases of complete paralysis of the respiratory muscles the respirator has a large margin of safety, the rocking bed none.From clinical observations made on 51 patients who were put upon the rocking bed—23 of them early in the course of the disease and 28 after they had been ill three months or more—it was concluded that the rocking bed is contraindicated for patients who are febrile and in whom the disease is progressing rapidly, and for those with atelectasis or urinary or pulmonary infection. It must be used with extreme care in the case of patients early in the course of the disease who are not tracheotomized, because of a tendency toward increased accumulation of mucus and the danger of atelectasis.General guides were developed with regard to use of the rocking bed for patients with post-acute poliomyelitis, and somewhat different rules were drawn for use of the apparatus in cases in which there is a chronic respiratory problem.The rocking bed will give artificial respiration in cases of respiratory weakness, but will not provide enough tidal air for the patient with paralysis of the muscles of respiration.     

The mechanism of mucus clearance in cough

An instability resembling an avalanche is proposed as the mechanism by which mucus is expelled from the respiratory tract during cough. The cough event was simulated in a model airway. In these experiments, air was forced through a channel whose walls were lined with a non-Newtonian material rheologically similar to tracheal mucus. Frames from high-speed cine photographs showed an unstable event which began as an undulation of the free surface and progressed to a catastrophic clearance of the channel. Measurements of the longitudinal pressure gradient support the hypothesis that the clearance event is initiated when the total stress applied to the mucus analog exceeds its finite yield stress. A continuum model predicts that yielding occurs within the bottom layers of the mucus analog. Calculations based upon estimates of tracheal geometry and air flow show that the clearance event studied here would be expected to occur during a cough but not during normal breathing. Experiments also show that a lubricant introduced between the channel walls and the mucus blanket can reduce the air flow rate required to precipitate the clearance.     

Genetic control of epithelial tube size in the Drosophila tracheal system

The proper size of epithelial tubes is critical for the function of the lung, kidney, vascular system and other organs, but the genetic and cellular mechanisms that control epithelial tube size are unknown. We investigated tube size control in the embryonic and larval tracheal (respiratory) system of Drosophila. A morphometric analysis showed that primary tracheal branches have characteristic sizes that undergo programmed changes during development. Branches grow at different rates and their diameters and lengths are regulated independently: tube length increases gradually throughout development, whereas tube diameter increases abruptly at discrete times in development. Cellular analysis and manipulation of tracheal cell number using cell-cycle mutations demonstrated that tube size is not dictated by the specific number or shape of the tracheal cells that constitute it. Rather, tube size appears to be controlled by coordinately regulating the apical (lumenal) surface of tracheal cells. Genetic analysis showed that tube sizes are specified early by branch identity genes, and the subsequent enlargement of branches to their mature sizes and maintenance of the expanded tubes involves a new set of genes described here, which we call tube expansion genes. This work establishes a genetic system for investigating tube size regulation, and provides an outline of the genetic program and cellular events underlying tracheal tube size control.     

Modulation of laryngeal and respiratory pump muscle activities with upper airway pressure and flow.

The hypothesis that upper airway (UA) pressure and flow modulate respiratory muscle activity in a respiratory phase-specific fashion was assessed in anesthetized, tracheotomized, spontaneously breathing piglets. We generated negative pressure and inspiratory flow in phase with tracheal inspiration or positive pressure and expiratory flow in phase with tracheal expiration in the isolated UA. Stimulation of UA negative pressure receptors with body temperature air resulted in a 10--15% enhancement of phasic moving-time-averaged posterior cricoarytenoid electromyographic (EMG) activity above tonic levels obtained without pressure and flow in the UA (baseline). Stimulation of UA positive pressure receptors increased phasic moving-time-averaged thyroarytenoid EMG activity above tonic levels by 45% from baseline. The same enhancement of posterior cricoarytenoid or thyroarytenoid EMG activity was observed with the addition of flow receptor stimulation with room temperature air. Tidal volume and diaphragmatic and abdominal muscle activity were unaffected by UA flow and/or pressure, whereas respiratory timing was minimally affected. We conclude that laryngeal afferents, mainly from pressure receptors, are important in modulating the respiratory activity of laryngeal muscles.     

FSI Analysis of a healthy and a stenotic human trachea under impedance-based boundary conditions

In this work, a fluid-solid interaction (FSI) analysis of a healthy and a stenotic human trachea was studied to evaluate flow patterns, wall stresses, and deformations under physiological and pathological conditions. The two analyzed tracheal geometries, which include the first bifurcation after the carina, were obtained from computed tomography images of healthy and diseased patients, respectively. A finite element-based commercial software code was used to perform the simulations. The tracheal wall was modeled as a fiber reinforced hyperelastic solid material in which the anisotropy due to the orientation of the fibers was introduced. Impedance-based pressure waveforms were computed using a method developed for the cardiovascular system, where the resistance of the respiratory system was calculated taking into account the entire bronchial tree, modeled as binary fractal network. Intratracheal flow patterns and tracheal wall deformation were analyzed under different scenarios. The simulations show the possibility of predicting, with FSI computations, flow and wall behavior for healthy and pathological tracheas. The computational modeling procedure presented herein can be a useful tool capable of evaluating quantities that cannot be assessed in vivo, such as wall stresses, pressure drop, and flow patterns, and to derive parameters that could help clinical decisions and improve surgical outcomes.     

Influence of the ventral surface of the medulla on tracheal responses to CO2

These studies investigated the role of the intermediate area of the ventral surface of the medulla (VMS) in the tracheal constriction produced by hypercapnia. Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. Airway responses were assessed from pressure changes in a bypassed segment of the rostral cervical trachea. Hyperoxic hypercapnia increased tracheal pressure and phrenic nerve activity. Intravenous atropine pretreatment or vagotomy abolished the changes in tracheal pressure without affecting phrenic nerve discharge. Rapid cooling of the intermediate area reversed the tracheal constriction produced by hypercapnia. Graded cooling produced a progressive reduction in the changes in maximal tracheal pressure and phrenic nerve discharge responses caused by hypercapnia. Cooling the intermediate area to 20 degrees C significantly elevated the CO2 thresholds of both responses. These findings demonstrate that structures near the intermediate area of the VMS play a role in the neural cholinergic responses of the tracheal segment to CO2. It is possible that neurons or fibers in intermediate area influence the motor nuclei innervating the trachea. Alternatively, airway tone may be linked to respiratory motor activity so that medullary interventions that influence respiratory motor activity also alter bronchomotor tone.     

Intravenous papain-induced cartilage softening decreases preload of tracheal smooth muscle

To study the interaction between tracheal cartilage and the trachealis muscle we measured trachealis muscle contraction in response to electrical field stimulation and methacholine in excised tracheal segments from control and papain-treated rabbits. Papain treatment softened the tracheal cartilage and altered the passive pressure volume curve of the tracheal segments at transmural pressures below 5 cmH2O. The transmural pressure required for maximal active changes in volume (isobaric contraction) with electrical field stimulation was increased in papain-treated animals. We conclude that tracheal cartilage provides a preload which stretches the trachealis muscle toward optimal length and that papain, by altering the elastic mechanical properties of cartilage, decreases this preload.     

Inspiratory rhythm in airway smooth muscle tone

In anesthetized paralyzed open-chested cats ventilated with low tidal volumes at high frequency, we recorded phrenic nerve activity, transpulmonary pressure (TPP), and either the tension in an upper tracheal segment or the impulse activity in a pulmonary branch of the vagus nerve. The TPP and upper tracheal segment tension fluctuated with respiration, with peak pressure and tension paralleling phrenic nerve activity. Increased end-tidal CO2 or stimulation of the carotid chemoreceptors with sodium cyanide increased both TPP and tracheal segment tension during the increased activity of the phrenic nerve. Lowering end-tidal CO2 or hyperinflating the lungs to achieve neural apnea (lack of phrenic activity) caused a decrease in TPP and tracheal segment tension and abolished the inspiratory fluctuations. During neural apnea produced by lowering end-tidal CO2, lung inflation caused no further decrease in tracheal segment tension and TPP. Likewise, stimulation of the cervical sympathetics, which caused a reduction in TPP and tracheal segment tension during normal breathing, caused no further reduction in these parameters when the stimulation occurred during neural apnea. During neural apnea the tracheal segment tension and TPP were the same as those following the transection of the vagi or the administration of atropine (0.5 mg/kg). Numerous fibers in the pulmonary branch of the vagus nerve fired in synchrony with the phrenic nerve. Only these fibers had activity which paralleled changes in TPP and tracheal tension. We propose that the major excitatory input to airway smooth muscle arises from cholinergic nerves that fire during inspiration, which have preganglionic cell bodies in the ventral respiratory group in the region of the nucleus ambiguus and are driven by the same pattern generators that drive the phrenic and inspiratory intercostal motoneurons.     

The Auditory Mechanics of the Outer Ear of the Bush Cricket: A Numerical Approach

Bush crickets have tympanal ears located in the forelegs. Their ears are elaborate, as they have outer-, middle-, and inner-ear components. The outer ear comprises an air-filled tube derived from the respiratory trachea, the acoustic trachea (AT), which transfers sound from the mesothoracic acoustic spiracle to the internal side of the ear drums in the legs. A key feature of the AT is its capacity to reduce the velocity of sound propagation and alter the acoustic driving forces of the tympanum (the ear drum), producing differences in sound pressure and time between the left and right sides, therefore aiding the directional hearing of the animal. It has been demonstrated experimentally that the tracheal sound transmission generates a gain of ∼15 dB and a propagation velocity of 255 ms⁻¹, an approximately 25% reduction from free-field propagation. However, the mechanism responsible for this change in sound pressure level and velocity remains elusive. In this study, we investigate the mechanical processes behind the sound pressure gain in the AT by numerically modeling the tracheal acoustic behavior using the finite-element method and real three-dimensional geometries of the tracheae of the bush cricket Copiphora gorgonensis. Taking into account the thermoviscous acoustic-shell interaction on the propagation of sound, we analyze the effects of the horn-shaped domain, material properties of the tracheal wall, and the thermal processes on the change in sound pressure level in the AT. Through the numerical results obtained, it is discerned that the tracheal geometry is the main factor contributing to the observed pressure gain.     

Stephen Hales: neglected respiratory physiologist

Stephen Hales was an eminent early 18th century scientist and minister of the parish of Teddington near London. He is well known for his early work on blood pressure. However, he made many contributions to respiratory physiology. He clarified the nature of the respiratory gases, distinguishing between their free (gaseous) and fixed (chemically combined) forms, demonstrated that rebreathing from a closed circuit could be extended if suitable gas absorbers were included (to remove carbon dioxide), suggested a similar device as a respirator for noxious atmospheres, invented the pneumatic trough for collecting gases, measured the size of the alveoli, calculated the surface area of the interior of the lung, calculated the time spent by the blood in a pulmonary capillary, invented the U-tube manometer, and measured intrathoracic pressures during normal and forced breathing. Hale's work is remarkable for its emphasis on the "statical" method, i.e., meticulous attention to detail in measurement and careful calculations. In his later life he made important contributions in the area of public health. He was a trustee of the new colony of Georgia and willed his own library of books to the colony though their whereabouts is unknown. He deserves more recognition in the history of respiratory physiology.     

Interrupter technique for measurement of respiratory mechanics in anesthetized cats

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg ip), airflow, changes in lung volume, and tracheal and esophageal pressures were measured. Airflow was interrupted by brief airway occlusions during relaxed expirations (elicited via the Breuer-Hering inflation reflex) and throughout spontaneous breaths. A plateau in tracheal pressure occurred throughout relaxed expirations and the latter part of spontaneous expirations indicating respiratory muscle relaxation. Measurement of tracheal pressure, immediately preceding airflow, and corresponding volume enabled determination of respiratory system elastance and flow resistance. These were partitioned into lung and chest wall components using esophageal pressure. Respiratory system elastance was constant over the tidal volume range, divided approximately equally between the lung and chest wall. While the passive pressure-flow relationship for the respiratory system was linear, those for the lung and chest wall were curvilinear. Volume dependence of chest wall flow resistance was demonstrated. During inspiratory interruptions, tracheal pressure increased progressively; initial tracheal pressure was estimated by backward extrapolation. Inspiratory flow resistance of the lung and total respiratory system were constant. Force-velocity properties of the contracting inspiratory muscles contributed little to overall active resistance.