Developmental signals do not further accentuate nonuniform postpneumonectomy compensatory lung growth.

Mechanical forces imposed on lung tissue constitute major stimuli for normal lung development and postpneumonectomy (PNX) compensatory growth and remodeling. Superimposing developmental signals on PNX signals augments compensatory alveolar growth but exaggerates airway-parenchymal dissociation (i.e., dysanaptic lung growth); the latter tends to offset benefits derived from the former. In adult dogs after PNX, lobar expansion and growth of the remaining lobes were markedly non-uniform (Ravikumar et al. J Appl Physiol 97:1567-1574, 2004). We hypothesized that superimposing developmental and post-PNX signals further accentuates nonuniformity of lobar growth. We used high-resolution computed tomography (HRCT) to follow regional lung expansion and growth in foxhounds undergoing right PNX at 2.5 mo of age compared with litter-matched control (Sham) animals; scans were performed 4 and 10 mo following surgery, i.e., before and after somatic maturity. Air and tissue volumes were measured in each lobe; tissue volume estimated by HRCT includes air-free tissue and blood in small vessels <1 mm. Interlobar nonuniformity of tissue volume was absent at 4 mo but evident 10 mo after PNX; growth of the remaining left lower lobe gradually lagged behind other lobes. At maturity, nonuniformity of lobar growth in pneumonectomized puppies was similar to that previously reported in pneumonectomized adults. We conclude that superimposing developmental and post-PNX signals enhances some aspects of compensatory lung growth and remodeling without altering its nonuniform spatial distribution.     

Changes in airway length after unilateral pneumonectomy in weanling ferrets

We have previously shown that airway cross-sectional area increases 15-20% after pneumonectomy in weanling ferrets by measuring bronchial casts. We have now reanalyzed these same casts to quantitate changes in airway length after pneumonectomy. In each cast the distance from each of 120 airways to the terminal bronchiole along its axial pathway was measured. The relationship between the logarithm of this distance and that of the fraction of the lobe subtended by an airway could be described by a quadratic equation with a correlation coefficient greater than 0.85. Subsegmental and more distal airways of postpneumonectomy animals were 33-47% longer than those of controls. Overall the main axial pathway of airways in the left lower lobes was 12% longer in operated animals, but this increase was primarily accounted for by an increase in the length of the more peripheral airways. Central airways were little if any longer in operated animals. After pneumonectomy in weanling ferrets, subsegmental and peripheral airway lengths increase to a greater degree than lung volume and airway cross-sectional area, whereas central airway lengths increase to a lesser extent if at all. The mechanisms responsible for this difference between central and intralobar compensatory airway growth are unknown.     

Postpneumonectomy airway growth in the ferret

To investigate the participation of the conducting airways in compensatory growth following partial lung resection, bronchial casts of six ferrets having undergone right-sided pneumonectomy at 8 wk of age were compared with those of five sham-operated control animals. At maturity, the left lungs of the postpneumonectomy animals were 65% larger than those of the controls. Central airway cross-sectional areas at 10 specific locations in each cast were 12% larger in the postpneumonectomy animals compared with controls. To characterize the size of more peripheral airways, the size and number of the terminal bronchioles subtended by each airway in each left lower lobe cast were identified so that the fraction of the lobe served by that airway could be estimated. The characteristic cross-sectional areas of airway serving 0.7, 2.2, and 9.5% of the left lower lobe in postpneumonectomy animals were 18, 13, and 13% larger than those of controls, but this difference was statistically significant only at the two more peripheral levels. Although airway areas were larger in postpneumonectomy animals, the ratio of airway cross-sectional area to the 0.67 power of lung volume was 20-26% smaller in operated than in control animals at each of the four levels. Following pneumonectomy in the weanling ferret, central and peripheral conducting airways increase in cross-sectional area to similar degrees, but this airway growth is less than the compensatory increase in lung volume.     

A comparative study of postpneumonectomy compensatory lung response in growing male and female rats.

Postpneumonectomy compensatory lung response and normal lung growth in the early postnatal period were studied in male and female rats. Four-week-old litter-matched male and female Sprague-Dawley rats were subjected to left pneumonectomy or sham operation and followed for 3 wk. In both sexes after pneumonectomy, lung weight (WL), lung volume (VL), alveolar surface area (Sw), total alveolar number (N(at)), and the amount of DNA and protein increased significantly. In both males and females, WL, VL, and Sw matched those of both lungs of the sham-operated group, but N(at) and the amount of DNA and protein did not. Female pneumonectomy and sham-operated rats were smaller in body weight than males. Absolute WL, VL, Sw, N(at), and the amount of DNA and protein were significantly lower, but specific parameters (per unit body weight) were significantly greater in females than in males. After pneumonectomy, the postcaval lobe increased most in volume (70 and 73% in males and females, respectively). Mean linear intercept and mean chord length of alveoli increased, and the number of alveoli per unit volume decreased more in the postcaval and middle lobes than in upper and lower lobes in both sexes. Postpneumonectomy, loss of elastic lung recoil was observed in females. We conclude that, in certain aspects (WL, VL), compensatory growth matched both lungs of controls, but in others (biochemical, morphometric) it did not. There was evidence of alveolar multiplication, but the dominant effect was enlargement of air spaces.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional lung growth following pneumonectomy assessed by computed tomography.

After pneumonectomy (PNX), mechanical strain on the remaining lung is greatly increased. To assess whether remaining lobes expand uniformly after left or right PNX (removing 42 and 58% of lung mass, respectively), we performed high-resolution computed tomography (CT) scans at 45 ml/kg above end-expiratory lung volume on adult male foxhounds after left or right PNX, which were compared with adult Sham controls. Air and tissue volumes were separately measured in each lobe. After left PNX, air and tissue volumes in the right upper and cardiac lobes increased approximately 2.2-fold above and below the heart, whereas volumes in right middle and lower lobes did not change significantly. After right PNX, air and tissue volumes in the left upper and middle lobes increased 2.3- to 2.7-fold across the midline anterior to the heart, whereas the left lower lobe expanded approximately 1.9-fold posterior to the heart. Regional changes in volume density of tissue post-PNX estimated by CT scan parallel postmortem estimates by morphometric analyses. Data indicate heterogeneous regional distribution of mechanical lung strain, which could influence the differential cellular compensatory response following right and left PNX.     

Pulmonary blood volume and edema in postpneumonectomy lung growth in rats

After pneumonectomy in young animals, the contralateral lung undergoes compensatory growth and generally attains the same weight and air space volume as both lungs in age-matched controls. In this study, we determined the contribution of lung edema and increased blood volume to the weight gain in rats. Three weeks after pneumonectomy (n = 18) or sham pneumonectomy (n = 17), the pulmonary blood volume and the extravascular water and albumin were evaluated by use of 51Cr-labeled erythrocytes and 125I-labeled albumin. The air space volume, blood-free lung weights, and DNA and protein content were also compared. The data show that the total pulmonary blood volumes and the blood volume per gram of blood-free dry lung were similar in pneumonectomized and age-matched sham controls. The total extravascular albumin and the extravascular albumin per gram of blood-free dry lung were also similar as well as the extravascular lung water, wet-to-dry weight ratios, DNA and protein content, and air space volumes. These data indicate that the increased weight of the postpneumonectomy lung was due to cellular and stromal proliferation. The blood volume and interstitial fluid increased in proportion to the increase in lung parenchyma. Neither vascular congestion nor increased extravascular protein and water contributed to the observed weight gain.     

Age-bodyweight relationships to lung growth in the F344 rat as indexed by lung weight measurements

Measurements of the total lung weights and the individual weights of the lung lobes of male F344 rats ranging in age from about 30 days to 140 days or more were made in order to determine how lung growth and the growths of the individual lung lobes relate to bodyweight over the course of maturation of this species. Additionally, in this study we also compared how each lung lobe grows relative to total lung growth, evaluated the ratios of lung dry weight to wet weight and obtained information on the weights of the trachea and extra-hilar main-stem bronchi as the F344 rat matures. The wet weights WLT of the trachea-lung preparations and the pooled lobe weights WPL as functions of rat bodyweight WB could be readily described by the following logarithmic expressions: WLT = 0.596 ln WB - 1.923, r = 0.95; WPL = 0.464 ln WB - 1.566, r = 0.96. Expressed as percentages of the pooled lobe weights, the individual lobes remained at constant values as the animals grew with the exception of the right caudal lobe which decreased between bodyweights of 72 and 96 g; absolute wet weight measurements of the individual lobes indicated that the right cranial, right middle and right intermediate lobes actually decreased in weight between bodyweights of 300 and 385 g. The dry weights of the lobes consistently represented approximately 22% of the wet weights regardless of animal age or bodyweight, and on average the airways represented about 20% of the weights of the intact airway-lung preparations over the course of animal maturation.     

Long-term consequences of compensatory lung growth

Left pneumonectomy or left nephrectomy was performed on 10-wk-old littermate male New Zealand White rabbits, and they were killed at 30 wk of age. Thirty-week-old male littermates served as controls. Nephrectomy was done to produce major tissue loss and trauma and to assess blood somatomedin C. At the end of the experiment, the right lungs of the pneumonectomy animals had a greater lung volume, weight, gas-exchanging surface area, and alveolar number than the nephrectomy animals and the controls, and their air spaces were the same size. When compared with both lungs of the nephrectomy group and the controls, lung weight was the same; lung volume, alveolar number, and protein were not significantly less in the pneumonectomy group, but gas-exchanging area (compared with controls only), DNA, and RNA were. After left nephrectomy, the right kidney increased in weight; nephrectomy had no effect on lung size or structure. We conclude that pneumonectomy at age 10 wk in male rabbits results in significant compensatory lung growth, including alveolar multiplication, and this persists to age 30 wk. Compensatory lung growth, however, was incomplete; that is, it did not reconstitute (equal) in all respects that of both lungs of the nephrectomy animals or the controls.     

Computed tomography of the thorax in rabbits: a prospective study in ten clinically healthy New Zealand White rabbits

Background

Literature investigating the normal cross-sectional anatomy of rabbits with computed tomography (CT) is sparse and incomplete. The purpose of the present study was to investigate the normal thoracic structures, in particular the cranial thorax, with CT angiography in 10 clinically healthy New Zealand White (NZW) rabbits.

Results

Absolute and relative measurements of the trachea, heart, thoracic caudal vena cava and aorta, right and left principal bronchi, right and left caudal lobar bronchi and the accompanying branches of the right and left pulmonary artery and vein, right and left lung volume and lung density were taken. The three lobes of the thymus (right ventral, right dorsal and left thoracic lobes) were identified in all rabbits. Both the right dorsal and left thoracic lobes of the thymus extended between the heart and thoracic wall in all individuals with the left lobe reaching more caudally in seven animals. Consequently, the craniocaudal extension of the left lung was smaller than the right lung in these rabbits. Volume of the left lung was significantly smaller than the right (P = 0.005). The cranial mediastinal, right and left tracheobronchial and the aortic thoracic lymph nodes were very small and identified in four, four, seven and ten rabbits, respectively. The heart took up a median of 4.0 intercostal spaces, and in seven rabbits, it was located in the 2nd–5th intercostal space. Median relative cardiac height and width measured 74 and 88%, respectively. The median angle of the trachea to the spine was 5°. Median density between the right and left lung did not significantly differ (? 549 and ? 583 Hounsfield units, respectively). In all but one rabbit, atelectasis was present and classified as mild, moderate or severe in six, two and one individuals, respectively. Mild subclinical bronchopneumonia was diagnosed in seven rabbits.

Conclusions

The present study provides species-specific anatomical CT information and reference values for structures in the thorax of the NZW rabbit. Subclinical bronchopneumonia appears to be a common CT finding.

     

Lung volumes after an increase in lung distension in pneumonectomized ferrets

To investigate the role of lung distension in compensatory lung growth, the right lung of each of 21 adult male ferrets was replaced with a silicone rubber balloon filled with mineral oil. Three to thirteen weeks after surgery, the oil was removed through a subcutaneous port. Lung volumes were measured serially until 3-6 wk after balloon deflation. With pneumonectomy the total lung capacity (TLC) decreased to less than 50% of the preoperative value and remained essentially unchanged while the balloon was inflated. At balloon deflation, TLC and vital capacity did not change immediately, whereas functional residual capacity increased by 44%, indicating a change of 2-3 cmH2O in end-expiratory transpulmonary pressure. TLC increased by 10% within 3 days and continued to increase over the subsequent 3-5 wk by a total of 25% over TLC at balloon deflation. There was little difference in this response between animals whose balloons were deflated 3 wk after surgery and those in which deflation was delayed up to 13 wk. After pneumonectomy in the adult ferret, the remaining lung increases in volume in response to an increase in lung distension even weeks or months after surgery. The extent to which this volume increase involves lung tissue growth or depends on previous lung resection is at present unknown. This model may be useful for studies of the mechanisms by which lung distension influences lung volume and compensatory lung growth.     

Postpneumonectomy alveolar growth does not normalize hemodynamic and mechanical function.

Immature foxhounds underwent 55% lung resection by right pneumonectomy (n = 5) or thoracotomy without pneumonectomy (Sham, n = 6) at 2 mo of age. Cardiopulmonary function was measured during treadmill exercise on reaching maturity 1 yr later. In pneumonectomized animals compared with Sham animals, maximal oxygen uptake, ventilatory response, and cardiac output during exercise were normal. Arterial and mixed venous blood gases and arteriovenous oxygen extraction during exercise were also normal. Mean pulmonary arterial pressure and resistance were elevated at a given cardiac output. Dynamic ventilatory power requirement was also significantly elevated at a given minute ventilation. These long-term hemodynamic and mechanical abnormalities are in direct contrast to the normal pulmonary gas exchange during exercise in these same pneumonectomized animals reported elsewhere (S. Takeda, C. C. W. Hsia, E. Wagner, M. Ramanathan, A. S. Estrera, and E. R. Weibel. J. Appl. Physiol. 86: 1301-1310, 1999). Functional compensation was superior in animals pneumonectomized as puppies than as adults. These data indicate a limited structural response of conducting airways and extra-alveolar pulmonary blood vessels to pneumonectomy and suggest the development of other sources of adaptation such as those involving the heart and respiratory muscles.     

The response of the pulmonary circulation to exercise during normoxia and hypoxia following pneumonectomy in the adult sheep

Pneumonectomy approximately halves the available pulmonary vascular bed. It is unknown whether the remaining lung has sufficient vascular reserve to cope with increased blood flow under stressful conditions without demonstrating abnormal pulmonary hemodynamics. To investigate this question, unanesthetized ewes with vascular catheters had hemodynamics assessed before and after a left pneumonectomy. Subsequently, on different days, the sheep were exercised on a treadmill under normoxic and hypobaric hypoxic (430 mmHg) (1 mmHg = 133.3 Pa) conditions. Pneumonectomy itself increased mean pulmonary arterial pressure by 4 mmHg. During normoxic or hypoxic exercise, the pneumonectomized sheep demonstrated a pulmonary hemodynamic response similar to normal sheep with two lungs. The pressure-flow relation for the right lung suggested the vascular reserve of the lung was not exceeded during exercise in the pneumonectomized sheep. Eighteen to 70 days after pneumonectomy there was no evidence of right ventricular hypertrophy, but there were small increases in the number of muscularized vessels less than 50 microns diameter and in the amount of muscle in normally muscularized pulmonary arteries. This study demonstrates that pneumonectomy slightly increases mean pulmonary arterial pressure. However, there is sufficient vascular reserve in the remaining lung to permit a normal hemodynamic response to exercise-induced increased blood flow even under hypoxic conditions.     

Endothelium-dependent relaxation differs in porcine pulmonary arteries from the left and right caudal lobes.

We hypothesized that pulmonary arteries (PA) from identical branch orders within left and right caudal lung lobes would exhibit similar vasomotor responses. Arterial rings from caudal lung lobes of female swine were examined in vitro. Vascular smooth muscle contraction to KCl and norepinephrine did not differ. Vascular relaxation to endothelium-dependent (bradykinin, acetylcholine, A-23187) and -independent (sodium nitroprusside, zero-calcium Krebs solution) vasodilators was assessed. Right PA exhibited less maximal relaxation to acetylcholine (50%) than did left PA (69%; P < 0.001). Maximal relaxation to sodium nitroprusside did not differ, although right PA had a lower drug concentration resulting in half-maximal relaxation (6.26 x 10(-8) M) than did left PA (9.57 x 10(-8) M; P < 0.05). Nitric oxide synthase inhibition with an arginine analog (N(omega)-nitro-L-arginine methyl ester) depressed acetylcholine-induced relaxation but the left vs. right difference persisted. Indomethacin enhanced relaxation to acetylcholine and abolished the difference between left and right. We conclude that endothelium-dependent vasorelaxation is less in porcine right than in left PA because of greater release of one or more constricting prostanoids in arteries from the right caudal lobe.     

Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice

Pneumonectomy results in rapid compensatory growth of the remaining lung and also leads to increased flow and shear stress, which are known to stimulate endothelial nitric oxide synthase (eNOS). Nitric oxide is an essential mediator of vascular endothelial growth factor-induced angiogenesis, which should necessarily occur during compensatory lung growth. Thus our hypothesis is that eNOS is critical for compensatory lung growth. To test this, left pneumonectomy was performed in eNOS-deficient mice (eNOS-/-), and compensatory growth of the right lung was characterized throughout 14 days postpneumonectomy and compared with wild-type pneumonectomy and sham controls. Compensatory lung growth was severely impaired in eNOS-/- mice, as demonstrated by significant reductions in lung weight index, lung volume index, and volume of respiratory region. Also, pneumonectomy-induced increases in alveolar surface density and cell proliferation were prevented in eNOS-/- mice, indicating that eNOS plays a role in alveolar hyperplasia. Compensatory lung growth was also impaired in wild-type mice treated with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester. Together, these results indicate that eNOS is critical for compensatory lung growth.     

Effect of pneumonectomy on the remaining lung in dogs

To determine the magnitude of functional compensation after pneumonectomy and whether compensation is related to maturity of the animal at the time of resection, we performed left pneumonectomy in either adult or 10-wk-old beagles. Studies were performed in adults 7-9 mo after surgery and in puppies 18-23 mo after surgery when the dogs reached full maturity. Results were compared with those in age- and sex-matched unoperated controls. Measurements included pressure-volume relationships, pulmonary hemodynamics, rebreathing studies of lung volume, diffusing capacity and its components, lung tissue volume, and pulmonary blood flow. Computerized-tomographic scans were performed in the puppy groups to determine changes in thoracic shape and size. Morphometric analysis of the lungs was performed under light microscopy. There was partial compensation for loss of one lung by functional improvement in the remaining lung. Compensation was greater in those pneumonectomized as puppies than as adults. Volume of the remaining lung was larger than predicted for a given transpulmonary pressure in both groups. Diffusing capacity, pulmonary capillary blood volume, and lung tissue volume were larger than expected for the normal right lung. After pneumonectomy, compliance of the rib cage was greater in puppies than in adults. Weight of the costal diaphragm was reduced in pneumonectomized puppies. Pulmonary hypertension at rest did not develop, and pulmonary vascular reactivity to hypoxia was unchanged after pneumonectomy in both groups. Significant correlations were obtained between physiological and morphometric measurements.     

Implications of post-pneumonectomy compensatory lung growth in pulmonary physiology and disease

In a number of species, partial pneumonectomy initiates hormonally regulated compensatory growth of the remaining lung lobes that restores normal mass, structure and function. Compensation is qualitatively similar across species, but differs with gender, age and hormonal status. Although the biology of response is best characterized in rats, dogs have proven valuable in defining post-operative physiological adaptations. Most recently, mice were recognized to offer unique opportunities to explore the genetic basis of the response, as well as to evaluate associated detrimental effects of pathophysiological significance in animals exposed to carcinogens. The pneumonectomy model thus offers powerful insight concerning adaptive organ growth.     

Alterations in enzymes related to adenosine 3',5'-monophosphate during compensatory growth of rat lung

Left pneumonectomy in rats induced growth of the right lung which was maximum one week after the operation. This compensatory lung growth was accompanied by an increase in adenylate cyclase/cyclic AMP phosphodiesterase activity suggesting an increase in the lung adenosine 3',5'-monophosphate (cyclic AMP) levels after pneumonectomy. Activities of cyclic-AMP-dependent protein kinase, phosphorylase and glucose 6-phosphatase were also increased suggesting the enhanced activity of the cascade system (glycogenolysis). Activities of these enzymes were maximally elevated during the first three days of operation and preceded the growth of contralateral lung, returning to the presurgery level on day 14. These data indicate that: (a) the biochemical response to pneumonectomy in rats appeared to be complete in two weeks and, (b) changes in the activities of cyclic-AMP-related enzymes may be important in the compensatory growth of rat lung.     

Lack of alveolar O2 during lung reperfusion does not decrease edema formation

We previously reported that pulmonary arterial occlusion for 48 h followed by 4 h of reperfusion in awake dogs results in marked edema and inflammatory infiltrates in both reperfused and contralateral lungs (Am. Rev. Respir. Dis. 134: 752-756, 1986; J. Appl. Physiol. 63: 942-950, 1987). In this experiment we study the effects of alveolar hypoxia on this injury. Anesthetized dogs underwent thoracotomy and occlusion of the left pulmonary artery. Twenty-four hours later the dogs were reanesthetized, and a double-lumen endotracheal tube was placed. The right lung was continuously ventilated with an inspiratory O2 fraction (FIO2) of 0.35. In seven study animals the left lung was ventilated with an FIO2 of 0 for 3 h after the left pulmonary artery occluder was removed. In six control animals the left lung was ventilated with an FIO2 of 0.35 during the same reperfusion period. Postmortem bloodless wet-to-dry weight ratios were 5.87 +/- 0.20 for the left lower lobe and 5.32 +/- 0.12 for the right lower lobe in the dogs with hypoxic ventilation (P less than 0.05 for right vs. left lobes). These values were not significantly different from the control dog lung values of 5.94 +/- 0.22 for the left lower lobe and 5.11 +/- 0.07 for the right lower lobe (P less than 0.05 for right vs. left lobes). All values were significantly higher than our laboratory normal of 4.71 +/- 0.06. We conclude that reperfusion injury is unaffected by alveolar hypoxia during the reperfusion phase.     

Partial pneumonectomy of telomerase null mice carrying shortened telomeres initiates cell growth arrest resulting in a limited compensatory growth response

Telomerase mutations and significantly shortened chromosomal telomeres have recently been implicated in human lung pathologies. Natural telomere shortening is an inevitable consequence of aging, which is also a risk factor for development of lung disease. However, the impact of shortened telomeres and telomerase dysfunction on the ability of lung cells to respond to significant challenge is still largely unknown. We have previously shown that lungs of late generation, telomerase null B6.Cg-Terc(tm1Rdp) mice feature alveolar simplification and chronic stress signaling at baseline, a phenocopy of aged lung. To determine the role telomerase plays when the lung is challenged, B6.Cg-Terc(tm1Rdp) mice carrying shortened telomeres and wild-type controls were subjected to partial pneumonectomy. We found that telomerase activity was strongly induced in alveolar epithelial type 2 cells (AEC2) of the remaining lung immediately following surgery. Eighty-six percent of wild-type animals survived the procedure and exhibited a burst of early compensatory growth marked by upregulation of proliferation, stress response, and DNA repair pathways in AEC2. In B6.Cg-Terc(tm1Rdp) mice carrying shortened telomeres, response to pneumonectomy was characterized by decreased survival, diminished compensatory lung growth, attenuated distal lung progenitor cell response, persistent DNA damage, and cell growth arrest. Overall, survival correlated strongly with telomere length. We conclude that functional telomerase and properly maintained telomeres play key roles in both long-term survival and the early phase of compensatory lung growth following partial pneumonectomy.     

The bronchial tree and lobular division of the chimpanzee lung

The bronchial ramification and lobular division in lungs of two chimpanzees (Pan troglodytes) were examined from the viewpoint of comparative anatomy, on the basis of the fundamental structure of bronchial ramification of the mammalian lung (Nakakuki, 1975, 1980). The right lung of the chimpanzee consists of the upper, middle, and lower lobes, whereas the left lung consists of the middle and lower lobes. The right and left lungs have the dorsal bronchiole system, lateral bronchiole system, and medial bronchiole system. The ventral bronchiole system is lacking on both sides. The right upper lobe is formed by the first branch of the dorsal bronchiole system. The right middle lobe is formed by the first branch of the lateral bronchiole system, and the right accessory lobe bronchiole is lacking. The remaining bronchioles constitute the right lower lobe. In the left lung, the upper and accessory lobes are lacking. The well developed middle lobe is formed by the first branch of the lateral bronchiole system. The left lower lobe is formed by the remaining bronchioles. Furthermore, these bronchioles are compared with those of the human lung byBoyden (1955).