Volume of the conducting airways calculated from morphometric parameters

A method of calculating the volume of a tree distal to a cut at the origin of a branch, using branching, diameter and length ratios, has been developed. The method was applied to bronchial tree casts from human, dog, sheep, hamster, and rat lungs. It was found that the exponenta in the equation weight=k×diameter ^a is approximately equal to 3.0 in sheep lung casts, as found by Hooper (1977), but it is greater than 3.0 in casts from the other four species.     

Why are there so many threat displays?

The morphology of branching trees in general, and of the bronchial tree in particular, can be described in terms of three parameters, the diameter, length and branching ratios. These are the factors by which mean diameter and mean length increase in successive orders towards the trachea, and by which the number of branches increases in successive orders away from the trachea. Orders of branching are counted from the periphery towards the trachea, according to the method of Strahler. A model of from two to nine orders, and of constant total length and volume, was used to investigate the effect of varying the above parameters on the calculated pressure difference across the model during flow. In particular, the branching ratio was set at known values for dog and human lungs, and diameter and length ratios were independently varied. Known data from dog and human lungs were found to be close to the points predicted by the model where the lines of minimal resistance and minimal entropy production crossed. Other factors which may affect the values of these parameters are discussed.     

Mechanical dissociation of bronchi from parenchyma in the immature piglet lung.

Previous studies of isolated piglet lungs suggested that local distending forces around bronchi might be relatively weak before postnatal growth and maturation. The present study used tantalum bronchograms to compare pressure-diameter relationships of bronchi in situ and after excision from the parenchyma in immature (3- to 7-day-old) and mature (3-mo-old) piglets. The mature group reproduced behavior that is well established in mature lungs from other species; i.e., bronchial diameters maintained a constant relationship to the parenchyma as the lungs were deflated from maximum to minimum volume. In sharp contrast, diameters failed to change until the immature lungs were deflated to <5 cmH(2)O transpulmonary pressure. Total percent change in bronchial diameter was then only 24% in the immature lungs compared with 47% in the mature lungs (P < 0.002). Total elastances of mature generation 3-8 bronchi did not change when they were excised from the parenchyma. However, in the same generations of immature bronchi, total elastances were lower after than before (1.06 vs. 1.60 cmH(2)O/%, P < 0.05) excision from the parenchyma. Elastances of the excised immature and mature bronchi were then the same (1.06 vs. 1.03 cmH(2)O/%, not significant). Because elastic moduli of the lung parenchyma are also similar in the two age groups, it was concluded that local features of airway-parenchyma coupling limited the generation of local parenchymal recoil around bronchi in the immature lungs.     

Distribution of airway narrowing responses across generations and at branching points,assessed in vitro by anatomical optical coherence tomography

Background

Previous histological and imaging studies have shown the presence of variability in the degree of bronchoconstriction of airways sampled at different locations in the lung (i.e., heterogeneity). Heterogeneity can occur at different airway generations and at branching points in the bronchial tree. Whilst heterogeneity has been detected by previous experimental approaches, its spatial relationship either within or between airways is unknown.

Methods

In this study, distribution of airway narrowing responses across a portion of the porcine bronchial tree was determined in vitro. The portion comprised contiguous airways spanning bronchial generations (#3-11), including the associated side branches. We used a recent optical imaging technique, anatomical optical coherence tomography, to image the bronchial tree in three dimensions. Bronchoconstriction was produced by carbachol administered to either the adventitial or luminal surface of the airway. Luminal cross sectional area was measured before and at different time points after constriction to carbachol and airway narrowing calculated from the percent decrease in luminal cross sectional area.

Results

When administered to the adventitial surface, the degree of airway narrowing was progressively increased from proximal to distal generations (r = 0.80 to 0.98, P < 0.05 to 0.001). This ''serial heterogeneity'' was also apparent when carbachol was administered via the lumen, though it was less pronounced. In contrast, airway narrowing was not different at side branches, and was uniform both in the parent and daughter airways.

Conclusions

Our findings demonstrate that the bronchial tree expresses intrinsic serial heterogeneity, such that narrowing increases from proximal to distal airways, a relationship that is influenced by the route of drug administration but not by structural variations accompanying branching sites.     

Degree of mineralization of pulmonary, tracheal and bronchial tissues in healthy persons of different age

In persons died an accidental or sudden death tissues of the lungs, bronchi of various caliber and trachea have been investigated by means of light microscopy and infrared (IR) spectroscopy. The IR spectra of the bronchial and tracheal tissue are identical and differ from the IR spectra of the pulmonary tissues. The mineralization degree (ratio of inorganic to organic components of the tissue) of the pulmonary tissue increases with age, in bronchi and trachea this dependence is expressed not so distinctly. The absolute mineralization degree in the bronchial tissue is 1.3-1.8 times higher than in the lungs. A suggestion is made that mineralization level of the tissue increases with aggravation of sclerosis processes.     

Characterization of nicotine-induced contraction in the canine bronchus

1. The modes of action of nicotine on the dog bronchial smooth muscle preparation was investigated, in order to compare with those on the bronchial preparations from the guinea-pig, rabbit and monkey. 2. Nicotine induced a contraction in the dog bronchial preparation, and this response was abolished by hexamethonium and atropine and potentiated by physostigmine. 3. These findings suggest that the contractile response to nicotine was mediated through an action on the nicotinic receptors and due to the release of acetylcholine. 4. Tetrodotoxin did not inhibit the contractile response to nicotine in the dog bronchial preparation, suggesting that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. 5. The present observations in the dog bronchial preparations coincided with those in the rabbit and monkey bronchi but not with the findings in the guinea-pig bronchus.     

Dynamic model of the bronchial tree

We present a distributed model of the bronchial tree which simulates the global dynamic characteristics of the lung. Local mechanical characteristics of each airway are represented by RCL circuits and parameters of the electrical components are determined from local physiological data. The bronchi geometry is described by Weibel's symmetric model, the flow in each airway is assumed laminar and mixing effects at the bifurcations are neglected; the transpulmonary pressure is assumed to be sinusoidal. In simulations of quiet breathing the resistance to airflow is found to be dominant, the flow amplitude decreasing as breathing frequency increases, but remaining almost constant in all the generations. Simulations of ventilation through obstructed lungs show frequency dependence of the dynamic characteristics in very compliant lungs. The global resistance to airflow and the dynamic compliance of the bronchi decrease as the forced oscillation frequency increases in a pattern similar to in vivo measurements in diseased lungs. This may be an outcome of the RCL properties of the network rather than due to uneven distribution of mechanical properties of the lung.     

Simulation of a steady-state mass-heat exchange in the respiratory tract

On the basis of Weibel respiratory tract model the mathematical model of mass and heat transfer in the lungs was solved for steady-state one-dimensional case. Coefficients of mass and heat transfer were taken from empirical expressions for canals. The model shows that independent water vapour or air heat saturation in the lungs occurs in 12-14 generations of the bronchial tree. The saturation site depends upon volume velocity of the air and functioning of the upper respiratory tract.     

Influence of vascular distending pressure on regional flows in isolated perfused dog lungs

To confirm the regional differences in vascular pressure vs. flow properties of lung regions that have been documented in zone 2 conditions [pulmonary venous pressure (Ppv) less than alveolar pressure], regional distending pressure vs. flow curves in zone 3 were generated by use of isolated blood-perfused dog lungs (3 right and 5 left lungs). Each lung was kept inflated at constant inflation pressure (approximately 50% of full inflation volume) while radioactively labeled microspheres were injected at different settings of Ppv. To achieve maximal vascular distension, Ppv was increased to approximately 30 cmH2O above alveolar pressure for the first injection. Subsequent injections were made at successively lower Ppv's. The difference between pulmonary arterial pressure and Ppv was kept constant for all injections. As was found in zone 2 conditions, there were differences in the regional distending pressure vs. flow curves among lung regions. To document the regional variability in the curves, the distribution of flow at a regional Ppv of 30 cmH2O above alveolar pressure was analyzed. There was a statistically significant linear gradient in this flow distribution from dorsal to ventral regions of the lungs but no consistent gradient in the caudad to cephalad direction. These results indicate that, even in near-maximally distended vessels, the dorsal regions of isolated perfused dog lungs have lower intrinsic vascular resistance compared with ventral regions.     

Pulmonary acinus: geometry and morphometry of the peripheral airway system in rat and rabbit

The geometry and morphometry of intraacinar airways in rat and rabbit lungs were studied from silicone rubber casts. Acini, defined as the complex of alveolated airways distal to the "terminal" bronchiole, were trimmed off the bronchial tree. In both species, the acinar volume followed a log-normal distribution over a range in size of one order of magnitude. At an inflation level of 60% total lung capacity, their mean volume was 1.86 mm3 in the rat and 3.46 mm3 in the rabbit. On a representative sample of acini of different volumes, the branching pattern was characterized as irregular dichotomy, and the segment length and inner and outer diameters were measured. The average acinus had a mean of six generations in the rat and seven in the rabbit. Both showed a decrease in segment length and inner diameter with each generation. The mean longitudinal pathway length--that is, the distance from the initial acinar segment to the terminal sacs--was found to depend on the cube root of the acinar volume in both species. It was calculated at 1.46 and 1.95 mm for rat and rabbit, respectively.     

Chromium content of normal and pathologically altered lung tissue

Flameless atomic absorption spectrophotometry was used to determine the chromium (Cr) content of samples taken at autopsy from the lungs, bronchi, and regional hilar lymph nodes of 50 randomly selected patients from urban and rural areas; these patients were not known to have been excessively exposed to Cr. On the average, the Cr concentration in the lungs of patients younger than 40 yr of age was approximately 2 μg/g; for patients over 40, the average Cr values were between 5 and 15 μg/g dry wt. The highest values were found in samples from the apex of the lung. The Cr concentration in lung and lymph nodes increased in proportion to age and the degree of anthracosis. Chromium content in the bronchial wall was very low in all cases. Chromium values up to ten times greater as compared to age-matched average values were found in scarred lung tissue, probably caused by a postinflammatory lymph vessel blockade. Slightly elevated Cr values were found in smokers' lungs. Chromium values in tissue from primary lung carcinomas (n=9) were lower than those in neighboring lung tissue. Based on the results of this study the amount of Cr of lung and bronchial tissue does not appear to be associated with the induction of bronchial carcinoma.     

Activation of smooth muscle in the airway wall, force production, and airway narrowing.

Airway narrowing depends on smooth muscle force production and muscle shortening, but the structural and geometric properties exhibited by individual generations of the bronchial tree largely determine the extent and characteristics of airway narrowing. Properties of major importance include the nature and integrity of the epithelium, the structural and mechanical properties of the airway wall, as well as airway diameter. The influence of these properties on airway narrowing measured as flow or flow resistance in large and small diameter segments of airways from pig lung is described using a novel preparation, the perfused bronchial segment.     

Sequence of interstitial liquid accumulation in liquid-inflated sheep lung lobes

In the initial stages of pulmonary edema, liquid accumulates in the lung interstitium and appears as cuffs around pulmonary vessels. To determine the pattern, rate, and magnitude of cuff formation, we inflated sheep lungs to capacity with liquid (inflation pressure 19 cmH2O) for 3-300 min. After freezing the lobes in liquid N2, we measured perivascular cuff size and total perivascular volume in frozen blocks of each lobe and compared the results with previous measurements in dog lungs. Total cuff volume in sheep lungs reached a maximum value of 5% of air space volume, compared with 9% in dog lungs. In sheep lungs 94% of vessels greater than or equal to 0.5 mm diam and 16% of smaller vessels were surrounded by cuffs. In dog lungs these values were 99 and 47%, respectively. The ratio of cuff area to vessel area reached a maximum of 2.3 in sheep lungs and 3.4 in dog lungs. In an electrical analogue model designed to simulate cuff growth, estimated interstitial resistance to liquid flow was 6-15 times higher than similar estimates in dog lungs. These species differences might be the result of differences in the composition of the interstitial gel or to differences in the mechanical linkage between the lung parenchyma and vessel wall.     

Increased coronary collateral blood flow. A possible mechanism of action for betahistine-HCl.

beta-Histine-HCl has been shown to be effective in modifying the size of developing myocardial infarcts. In the present study the hypothesis that beta-histine increases the flow of blood through collateral channels and thus supplies blood to ligated areas of the myocardium was investigated in the dog. The methods used were measurement of retrograde coronary blood flow and angiography after coronary artery ligation. beta-Histine administration for 6 h increased retrograde blood flow 68.2--91.0% over controls. Coronary angiography demonstrated the existence of collateral channels 200--400 micrometer in diameter within the myocardium after ligation and 4 h of beta-histine administration.     

Relation between pulsus paradoxus and pulmonary function in patients with chronic airways obstruction.

The relation of pulsus paradoxus to chronic, stable obstructive disease of the airways has not previously been described. Pulsus paradoxus was observed in 66% of 68 patients with such disease but in none of 14 healthy individuals. There was a significant correlation between the degree of pulsus paradoxus and the forced expiratory volume in 1 second (FEV1) in the subgroup of patients with bronchial asthma but not in the subgroup with chronic bronchitis or emphysema, or both. There was no correlation between the degree of pulsus paradoxus and the degree of hyperinflation in either group. Hence factors other than hyperinflation contribute importantly to the decrease in systolic pressure that occurs at full inflation of the lungs.     

A fractal analysis of the radial distribution of bronchial capillaries around large airways.

We analyzed published measurements of the bronchial circulation and airway wall (Anderson JC, Bernard SL, Luchtel DL, Babb AL, and Hlastala MP. Respir Physiol Neurobiol 132: 329-339, 2002) and determined that the radial distribution of bronchial capillary cross-sectional area was fractal. We limited our analysis to bronchial capillaries, diameter < or =10 mum, that resided between the epithelial basement membrane and adventitia-alveolar boundary, the airway wall tissue. Thirteen different radial distributions of capillary-to-tissue area were constructed simply by changing the number of annuli (i.e., the annular size) used to form each distribution. For the 13 distributions created, these annuli ranged in size from to of the size of the airway wall area. Radial distributions were excluded from the fractal analysis if the sectioning procedure resulted in an annulus with a radial thickness less than the diameter of a capillary. To determine the fractal dimension for a given airway, the coefficient of variation (CV) for each distribution was calculated, and ln(CV) was plotted against the logarithm of the relative piece area. For airways with diameter >2.4 mm, this relationship was linear, which indicated the radial distribution of bronchial capillary cross-sectional area was fractal with an average fractal dimension of 1.27. The radial distribution of bronchial capillary cross-sectional area was not fractal around airways with diameter <1.5 mm. We speculated on how the fractal nature of this circulation impacts the distribution of bronchial blood flow and the efficiency of mass transport during health and disease. A fractal analysis can be used as a tool to quantify and summarize investigations of the bronchial circulation.     

Cholinesterase-containing nerve fibres on blood vessels in lungs of some laboratory mammals

Summary Distribution of cholinesterase-containing nerve fibres on blood vessels in the lungs of rats, mice, rabbits, guinea pigs, cats, dogs, and rhesus monkeys has been studied with the thiocholine method modified by Coupland and Holmes and with the direct-coloring method according to Karnovsky and Roots. The presence of acetylcholinesterase positive nerve fibres on the pulmonary arteries has been established only in four species of the studied animals, namely the cat, the dog, the rhesus monkey and the rabbit. These nerves form d distinct plexus on the border between the media and adventitia. In the thick walled perihilar branches of the pulmonary artery of the rabbit the nerve fibres penetrate—as a rule—into the outer half of the media. Despite many times repeated experiments and careful investigations no nerve fibres have been found on the intrapulmonary branches of the blood vessels in the lungs of rats, mice, and guinea pigs. In the walls of the pulmonary veins, with the exception of the pulmonary veins in the rat and the mouse, cholinesterase fibres have been identified only seldom. Acetylcholinesterase nerve fibres in medio-adventitial localization have also been found in the walls of bronchial arterioles, this being the case in all the species under study. Bronchial veins do not exhibit any nerve fibres. The distribution of the acetylcholinesterase-containing nerve fibres on the pulmonary arteries is different from species to species.     

Effect of increased static lung recoil on bronchial dimesions of excised lungs.

We measured bronchial diameters and lengths during static deflation and inflation in eight excised dog lobes before and after static lung recoil (Pst(L)) had been significantly increased by cooling the lobe for 48 h at 4 degrees C and ventilating it for 3 h. In control lobes, bronchial diameters were the same at any volume even though Pst(L) was different during inflation and deflation. These results agree with those of Hughes et al. (J. Appl. Physiol. 32: 25-35, 1972). However, when Pst(L) was increased, diameters at a given volume were significantly increased over control values; diameters at a given pressure were nearly the same as the controls. Therefore, under these conditions, bronchial diameter did not conform to lung volume. The ventilation process appeared to alter the circumferential elastic properties of the bronchi because diameters at all pressures were slightly larger after ventilation. Bronchial length-volume relationships were the same in both control and ventilated lobes. Thus, when Pst(L) was markedly increased, diameter corresponded best to lung recoil and length to lung volume.     

Routes of protein transport into the lungs from the bronchial vascular system

In order to study the role of the bronchial vascular system in pulmonary protein transport, experiments have been performed in 6 anesthesized dogs, 16 isolated canine lungs and 10 white rats. When bilateral ligation of the bronchial arteries is performed in the anesthesized dogs, cessation of the bronchial blood stream results in decreasing protein transport and lymph outflow from the lungs. In the isolated canine lungs perfused through the pulmonary and bronchial vessels, lymph formation is determined by presence of the bronchial perfusion. As demonstrated the electron microscopical investigations with the marker of the protein transport--horseradish peroxidase--for 15 min of observation the marker does not get out of the limits of endothelium in the pulmonary capillaries. During this time horseradish peroxidase gets out of the bronchial vessels into the loose connective tissue of the lung, the lymphatic capillaries and the alveolar epithelium. Therefore, it is possible to make a conclusion on a predominated role of the protein transport in the lungs out of the bronchial vascular system as compared to the pulmonary system.