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PubMed1997

Effect of transmural pressure on preloads and collapse of immature bronchi.

Immature airways are highly compliant compared to the adult, suggesting that trachea and bronchi from immature animals may be easily compressed. Although tracheal compression has been extensively studied, the effect of transmural pressure on occlusion of immature bronchi has been neglected. The transmural pressure at which the lumen closed was determined from the transmittance of pressure along the lumen of isolated bronchi from late-term foetal, 1 and 4 week old pigs. Bronchi from eight cases of sudden infant death syndrome (SIDS) were also studied. In several experiments, smooth muscle tone was produced either by electrical field stimulation or carbachol challenge, and the relationship between active muscle tone and resting transmural pressure was studied. Bronchi from foetal, 1 and 4 week old pigs were occluded by intraluminal pressures of -4, -5 and -24 cmH2O. SIDS bronchi closed at -11 cmH2O. Histological and endoscopic investigations showed that closure of the bronchi occurred along a plane and was not uniform along the bronchus. Carbachol precontraction increased the transmural pressure required to close bronchi by approximately 5 cmH2O. The relationship between muscle tone and resting pressure was the same in all age groups, except when transmural pressure was at or below closing pressure. Bronchi from immature animals and human infants are vulnerable to collapse by small changes in transmural pressure. Bronchial closure is partly dependent on smooth muscle tone, particularly in younger animals.

Aging↗
PubMed1988

Basilar segmental bronchi: thin-section CT evaluation.

Thin (1.5- and 5.0-mm) section contiguous computed tomographic (CT) scans obtained through the basilar segmental bronchi in 31 patients were reviewed in order to delineate normal anatomy and common variations of lower lobe airways. In each case, the frequency with which individual segmental and subsegmental bronchi were seen was established, as were variations in branching patterns. All basilar segmental bronchi were identified except in one case in which images of the left lung were obscured due to respiratory and cardiac motion. In the right lung, a division into subsegmental bronchi was identified in 84 of 150 (56%) visualized segmental bronchi. Six separate patterns of basilar segmental subdivision were found. In the left lung, subsegmental bronchi were identified arising from 51 of 145 (35%) visualized segmental bronchi. Five separate patterns of bronchial subdivision were found in the left lung. It is concluded that thin-section CT allows precise identification of all basilar segmental bronchi and, consequently, can play a significant role in the cross-sectional evaluation of lower lobe bronchial and parenchymal abnormalities.

Bronchi↗
PubMed1982

Isovolume pressure-flow relationships in intrapulmonary bronchi of excised dog lungs.

From excised dog lungs we isolated airtight the intrapulmonary main bronchi (5-6 cm in length) with beads according to the technique described by Takishima et al. (J. Appl. Physiol. 38: 875-881, 1975), except for the most distal bronchus in which a retrograde catheter was inserted into the pleural surface of the lung. Air flowed from the retrograde catheter to the isolated main lobar bronchi at a given transpulmonary pressure (PL) with variable dynamic rates of driving pressure. We studied isovolume pressure-flow (IVPF) curves in the isolated intrapulmonary bronchi. The IVPF curves showed maximum expiratory flow (Vmax) and negative effort dependence. Vmax increased with increased PL and with increased dynamic rate of driving pressure and decreased with increased peripheral airway resistance added to the retrograde catheter. Bronchograms showed that dynamic compression occurred near the outlet of the isolated bronchi. When the isolated bronchi were dissected free from the surrounding parenchyma, Vmax decreased by 20-30% compared with Vmax in intact bronchi. We concluded that Vmax in intrapulmonary bronchi is preserved by mechanical interdependence between bronchi and parenchyma.

Animals↗
PubMed1999

Subjective differentiation of normal and pathological bronchi on thin-section CT: impact of observer training.

The effect of observer training on sensitivity, specificity and interobserver agreement in the differentiation between normal and pathological bronchi on computed tomography (CT) was studied. The wall thickness of bronchi with normal walls and with pathologically thickened walls were subjectively scored by three independent observers before and after a training period of 2 weeks. Sensitivity, specificity and interobserver agreement were calculated for reading sessions before and after training. Increase and decrease in agreement after training were determined. There was a statistically significant difference (p=0.001) between objectively measured wall thickness of normal and pathological bronchi, both for reference bronchi and for bronchi used for reading sessions. While training increased interobserver agreement, it had no effect on sensitivity (0.46 versus 0.44 after training) and specificity (0.71 versus 0.72 after training) in detecting pathological bronchi. Increased agreement after training was significantly (p=0.001) more frequent than decreased agreement. There is a discrepancy between the effect of training on interobserver agreement and on sensitivity and specificity in the subjective differentiation between normal and pathological bronchi. Interobserver agreement alone is not a reliable indicator of a beneficial effect of training in the evaluation of this parameter.

Bronchi↗
PubMed1988

Pressure-volume and length-stress relationships in canine bronchi in vitro.

Intraparenchymal canine airway segments with branches tied off were mounted between two fluid-filled cannulas in an organ chamber. Airways were inflated to successive volumes ranging from 4 to 100% of the segment volume at 25 cmH2O. At each volume, pressure was monitored during isovolumetric contractions elicited by 10(-3) M acetylcholine. Small bronchi developed pressures greater than 30 cmH2O in response to acetylcholine at all volumes and were able to constrict to closure. Large bronchi developed pressures greater than 30 cmH2O only near maximal volumes and were able to constrict to only 30% of maximal volume. Maximal active pressures occurred at low volumes in small bronchi and at high volumes in large bronchi. However, maximal active circumferential tension and stress occurred at near-maximal volumes in both large and small bronchi. Circumferential length active-stress curves and maximal active-stress development for bronchi and trachealis muscle strips were similar. Similar length active-stress properties in different bronchi may produce significant differences in volume-pressure characteristics.

Animals↗
PubMed2001

NK1 receptor stimulation causes contraction and inositol phosphate increase in medium-size human isolated bronchi.

Although contraction of human isolated bronchi is mediated mainly by tachykinin NK2 receptors, NK1 receptors, via prostanoid release, contract small-size (approximately 1 mm in diameter) bronchi. Here, we have investigated the presence and biological responses of NK1 receptors in medium-size (2-5 mm in diameter) human isolated bronchi. Specific staining was seen in bronchial sections with an antibody directed against the human NK1 receptor. The selective NK1 receptor agonist, [Sar(9), Met(O2)(11)]SP, contracted about 60% of human isolated bronchial rings. This effect was reduced by two different NK1 receptor antagonists, CP-99,994 and SR 140333. Contraction induced by [Sar(9), Met(O2)(11)]SP was independent of acetylcholine and histamine release and epithelium removal, and was not affected by nitric oxide synthase and cyclooxygenase (COX) inhibition. [Sar(9), Met(O2)(11)]SP increased inositol phosphate (IP) levels, and SR 140333 blocked this increase, in segments of medium- and small-size (approximately 1 mm in diameter) human bronchi. COX inhibition blocked the IP increase induced by [Sar(9), Met(O2)(11)]SP in small-size, but not in medium-size, bronchi. NK1 receptors mediated bronchoconstriction in a large proportion of medium-size human bronchi. Unlike small-size bronchi this effect is independent of prostanoid release, and the results are suggestive of a direct activation of smooth muscle receptors and IP release.

Analysis of Variance↗
PubMed2002

Relaxation of proximal and distal isolated human bronchi by halothane, isoflurane and desflurane.

Volatile anaesthetics relax airway smooth muscle in vitro. The amount of relaxation might depend on the type and concentration of volatile anaesthetics, the calibre and precontraction level of the bronchi, and also on the species considered. These effects were investigated on isolated human bronchi. Isometric relaxations produced by halothane, isoflurane and desflurane bubbled on human bronchial rings precontracted with carbachol were recorded and compared with time controls. Volatile anaesthetics induced a concentration-dependent relaxation at 0.66, 1.33 and 2 minimum alveolar concentration (MAC). The relaxation was greater in mildly (carbachol 3x10(-7) M) than in highly (carbachol 2x10(-6) M) precontracted bronchi. Halothane was more potent in relaxing distal as compared to proximal bronchi; this differential effect was less pronounced with isoflurane and not observed with desflurane. While the three volatile anaesthetics induced similar relaxation on proximal bronchi, halothane was significantly more potent than desflurane on distal bronchi, with isoflurane being intermediate. The relaxation induced by 1.33 MAC of halothane, isoflurane and desflurane on moderately precontracted distal bronchi (carbachol 1x10(-6) M) was attenuated by pretreatment with glibenclamide 1x10(-5) M. In conclusion, halothane, isoflurane and desflurane exert direct but differential relaxant effects on human isolated bronchial smooth muscle. This may provide supplemental bronchodilation during anaesthesia. Although adenosine triphosphate-sensitive K+ channels are involved in these relaxant effects, they are unlikely to explain the observed differences between the three volatile anaesthetics.

Anesthetics, Inhalation↗
PubMedDate not supplied

Localization of double, roentgenographically occult lung cancer. Cytologic findings from selective brushing of all segmental and subsegmental bronchi.

Using selective brushing of all segmental and subsegmental bronchi, six patients were diagnosed as having synchronous, double, roentgenographically occult lung cancers. Experienced bronchoscopists failed to detect four "second cancer" lesions in six patients. The appearance of atypical cells as shown by cytologic examination indicated the probability of the presence of cancer in the examined bronchus. Single cancer cells or tiny clusters of cells with orangeophilic cytoplasm can appear in specimens obtained from all bronchi, and such cells should not be considered to have originated in the bronchi under examination. Medium-sized or large clusters of cancer cells without degeneration and with basophilic cytoplasm appear only in specimens obtained from bronchi in which a cancer lesion exists, and thus they should be considered to have originated in the bronchi under examination. Cancer cells with orangeophilic cytoplasm in clusters should be considered to have originated in unknown locations. To determine the origin of such cells, one must compare the specimens with those obtained from other segmental and subsegmental bronchi. Our findings suggest that selective brushing of all segmental and subsegmental bronchi is a useful method of detecting unrecognizable second cancers and that the method should be employed for all patients with positive sputum cytology.

Aged↗
PubMed1990

15(S)-hydroxyeicosatetraenoic acid is the major arachidonic acid metabolite in human bronchi: association with airway epithelium.

15(S)-Hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) was by far the most abundant metabolite of arachidonic acid in chopped human bronchi, as identified by reverse phase HPLC, uv spectrometry, and GC/MS. The quantitation of monohydroxyeicosatetraenoic acids (mono-HETEs) was performed by the use of 16(S)-hydroxy-9(Z),12(Z),14(E)-heneicosatrienoic acid as internal standard. Thus, significant amounts of 15-HETE were obtained in incubations of bronchi in buffer alone, but the addition of exogenous arachidonic acid (3-100 microM), dose-dependently increased the formation, with maximal levels reached at around 10 min. In contrast, challenge with ionophore A23187 or anti-human IgE did not stimulate the production of 15-HETE in the bronchi. Nordihydroguaiaretic acid inhibited the production of 15-HETE, whereas indomethacin did not. Small amounts of 8,15-diHETEs were detected in incubations with exogenous 15H(P)ETE. Lipoxins were however not detected under any of the incubation conditions used. Furthermore, removal of the airway epithelium substantially diminished the production of 15-HETE in the bronchi. Finally, bronchi were obtained from three patients with asthma, and the amounts of 15-HETE in these specimens were significantly higher than those found in tissues from nonasthmatics. Also, in peripheral lung parenchyma and pulmonary blood vessels 15-HETE was the major mono-HETE after stimulation with arachidonic acid but the levels were about 10 times lower than in the bronchi. As another difference, challenge of the parenchyma with the ionophore A23187 made 5-HETE the predominant mono-HETE. Taken together, airway epithelium appears to be the major source of 15-HETE in the human lung and the findings in specimens of asthmatics raise the possibility that 15-HETE somehow is involved in airway inflammation.

Arachidonic Acid↗
PubMed1996

Increased response to antigen and histamine release in smaller sensitized canine bronchi.

We studied the Schultz-Dale response in vitro in large and small size branches from 3rd to 6th generation bronchi from ragweed-sensitized dogs. The response to electric field stimulation (EFS) increased after antigen from 65.56 +/- 8.11 to 78.6 +/- 9.0 mN/mm2 of smooth muscle (P < 0.01), but no topographical difference was observed. The response to ragweed (% of the response to EFS) was 158.3 +/- 12 and 67.1 +/- 11.7 in strips from small and large branches respectively (P < 0.01), while no difference was observed between generations; when clustering bronchi according to dimension, it was 129.9 +/- 13.4 in small and 71.9 +/- 19.8 in large bronchi (P < 0.01). Histamine released from small and large branches was 2.90 +/- 1.01 and 0.76 +/- 0.20 (ng/mg of tissue) respectively (P < 0.05); no difference was found between generations. In conclusion, in sensitized dogs a greater response to antigen, which involves a higher histamine release, occurs in small compared to large bronchi. We suggest that control of distribution of ventilation occurs mainly at small bronchi level, which becomes the elective tissue to study the Schultz-Dale response. Finally, the classification of bronchi into generations is inadequate to study allergic bronchospasm.

Allergens↗
PubMed2001

Endothelin-1 increases cholinergic nerve-mediated contraction of human bronchi via tachykinin synthesis induction.

1. In some asthmatics, muscarinic receptor antagonists are effective in limiting bronchoconstrictor response, suggesting an abnormal cholinergic drive in these subjects. There is a growing body of evidences indicating that cholinergic neurotransmission is also enhanced by endothelin-1 (ET-1) in rabbit bronchi, mouse trachea and in human isolated airway preparations. 2. We investigated the role of secondary mediators in ET-1 induced potentiation of cholinergic nerve-mediated contraction in human bronchi, in particular the possible role of neuropeptides in this phenomenon. 3. Bronchial tissues after endothelin treatment were exposed to a standard electrical field stimulation (EFS) (30% of EFS 30 Hz)-induced contraction. In addition, in some experiments, preparations were treated with a tachykinin NK(2) receptor antagonist and subsequently exposed to the same protocol. HPLC and RIA were performed on organ bath fluid samples. Moreover, the human bronchi were used for the beta-PPT (preprotachykinin) mRNA extraction and semiquantitative reverse transcription polymerase chain reaction (RT - PCR), prior to and 30-40 min following ET-1 challenge. 4. The selective tachykinin NK(2) receptor antagonist, SR48968, was effective to reduce ET-1 potentiation of EFS mediated contraction. HPLC or RIA showed significant increased quantities of NKA in organ bath effluents after EFS stimulation in bronchi pretreated with ET-1. Finally, beta-PPT mRNA level after stimulation of bronchi with ET-1 was increased about 2 fold respect to control untreated bronchi. 5. In conclusion, this study demonstrated that, at least in part, the ET-1 potentiation of cholinergic nerve-mediated contraction is mediated by tachykinin release, suggesting that in addition to nerves, several type of cells, such as airway smooth muscle cell, may participate to neuropeptide production.

Acetylcholine↗
PubMed1996

Necessity of dual blockade of endothelin ETA and ETB receptor subtypes for antagonism of endothelin-1-induced contraction in human bronchi.

1. Endothelin (ET)-1 has been postulated to be involved in the development of obstructive airway diseases in man. In the present study, we attempted to characterize ET receptor subtypes mediating ET-1-induced contraction in human isolated bronchi. The ET receptor antagonists used in the present study were BQ-123 (ETA receptor-selective), BQ-788 (ETB receptor-selective) and BQ-928 (ETA/ETB dual). Sarafotoxin S6c (S6c) was also used as an ETB receptor-selective agonist. 2. In human bronchi, ET-1 and S6c (10(-12)M to 10(-7) M) produced concentration-dependent contraction with almost equal potency (pD2: 8.88 +/- 0.16 for ET-1 and 9.42 +/- 0.15 for S6c). The contraction induced by S6c was competitively antagonized by BQ-788 alone (1 and 10 microM) with a pKB value of 7.49 +/- 0.21, suggesting that the stimulation of ETB receptors causes a contraction of human bronchi. However, contrary to expectation, the concentration-response curves for ET-1 were not affected by BQ-788. The ET-1- and S6c-induced contractions were not affected by BQ-123 (10 microM). Thus, ET-1-induced contraction of human bronchi is not antagonized by BQ-123 alone or by BQ-788 alone. 3. Combined treatment with 10 microM BQ-123 and 10 microM BQ-788 significantly antagonized the contraction induced by ET-1 with a dose-ratio of 11. BQ-928 also significantly antagonized ET-1-induced contraction with a pKB value of 6.32 +/- 0.24. 4. The specific binding of [125I]-ET-1 to human bronchial membrane preparations was inhibited by BQ-123 (100 pM to 1 microM) by approximately 40%. Combination treatment with BQ-788 (100 pM to 1 microM) completely inhibited the BQ-123-resistant component of [125I]-ET-1 specific binding. 5. In conclusion, the present study demonstrates that BQ-788 alone cannot inhibit ET-1-induced contractions in human bronchi, although human bronchial ETB receptors are BQ-788-sensitive. Furthermore, it was shown that blockade of both receptor subtypes antagonizes ET-1-induced contraction, and that both receptor subtypes co-exist in human bronchial smooth muscles. These findings suggest that ETA receptors as well as ETB receptors are involved in ET-1-induced contraction in human bronchi. If ET-1 is involved in human airway diseases, dual blockade of ETA and ETB receptors may be necessary to treat the diseases.

Adult↗
PubMed1994

Evidence for preservation of epithelial function in cryopreserved porcine and human bronchi.

Porcine and human bronchi have been investigated in vitro without or after storage at -196 degrees C in Krebs-Henseleit solution containing 2.0 M dimethyl sulphoxide and 0.1 M sucrose as cryoprotectants. In bronchi from both species maximal post-thaw contractile responses to acetylcholine (ACh) were reduced by about 25-30% compared to unfrozen bronchi. To assess the viability of bronchi and endothelium-denuded rat aortic strips, was employed. The release of an epithelium-derived inhibitory factor (EpDIF) was induced by ACh and assessed in terms of concentration-dependent relaxation of the endothelium-denuded rat aortae. Following removal of bronchial epithelium, ACh failed to elicit any relaxation of rat aorta. With cryopreserved bronchi from both pig and human about 5 and 30 times higher concentrations of ACh, respectively, were required to elicit the same relaxant response as with unfrozen bronchi. The results suggest that after the freezing-thawing process both smooth muscle and epithelial function is largely preserved and provide support for the use of cryopreservation for storage of airway preparations for pharmacological studies.

Acetylcholine↗
PubMed2000

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.

Age Factors↗
PubMed1989

Structural changes in airways of rats exposed to nitrogen dioxide intermittently for seven days. Comparison between major bronchi and terminal bronchioles.

Structural changes caused by exposure to NO2 were compared between the largest intrapulmonary bronchi (major bronchi) and the terminal bronchioles. Rats were exposed to 50 ppm NO2 for 5 h a day for 7 consecutive days, and microscopic findings were assessed subjectively and quantitatively. Destruction of airway epithelium was present on Day 1, and the reparative phase was observed between Days 3 and 7. Light microscopy showed that on Day 1, loss of cilia and disintegration of epithelium occurred, and that the latter was worse in major bronchi than in terminal bronchioles; apical projections of Clara cells in terminal bronchioles were lost almost totally. Recovery of epithelium began by Day 3 and cilia by Day 5, and ciliogenesis progressed less promptly in terminal bronchioles. Clara cells did not return to normal during the experiment. Furthermore, a decrease in the airway diameter occurred in peripheral airways along with an increase in mural thickness in terminal bronchioles. Mural inflammation was also seen more conspicuously in terminal bronchioles. Electron microscopy revealed that epithelial cells lost secretory granules on Day 1 and began to repair them by Day 5 in major bronchi and by Day 7 in terminal bronchioles. It is likely that epithelium in terminal bronchioles is not particularly sensitive to NO2 compared with that in major bronchi, but that recovery occurs more promptly in major bronchi than in terminal bronchioles. Mechanisms underlying bronchoconstriction occurring preferentially in peripheral airways are also discussed.

Animals↗
PubMed1996

Contractile endothelin-B (ETB) receptors in human small bronchi.

Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.

Acetylcholine↗
PubMed1998

Concurrent measurement of smooth muscle shortening, lumen narrowing and flow to acetylcholine in large and small porcine bronchi.

Models of airway function indicate that responsiveness (flow reduction) to bronchoconstrictor provocation depends on airway smooth muscle shortening and airway wall morphology. The contribution of these factors to the responsiveness of central and peripheral bronchi was assessed. Lumen flow was recorded in porcine perfused small (2 min i.d.) and large bronchial segments (6 mm i.d.). Lumen diameter was recorded in the same airways after inserting an endoscope. Smooth muscle shortening, relative wall area (WAr), smooth muscle and cartilage thickness and mucosal folds were measured morphometrically. The effect of acetylcholine (ACh; 10(-6)-10(-1) M) on functional measurements was determined by curve fitting. Maximum muscle shortening was 30% in small and 19% in large bronchi (p<0.01) and lumen narrowing was 49% and 39%, respectively. High doses of ACh stopped flow in small bronchi, but produced a plateau in large bronchi. Small airways were 250-times more sensitive to ACh than large airways, for all measurements. Smooth muscle and cartilage thickness and numbers of mucosal folds were greater in large than in small bronchi (p< or =0.01). Lumen narrowing and flow reduction were greater than predicted on the basis of muscle shortening and WAr (p<0.05). The structure of airways from the two groups was qualitatively similar, but responses were markedly different. Greater narrowing and flow responses of small bronchi were directly associated with smooth muscle responsiveness in situ. The results suggest that in vivo changes in airway wall shape or dimensions, or luminal secretions, exert a significant effect on airway flow, particularly in the small airways.

Acetylcholine↗
PubMed1992

Relationship of cytochrome P-450 activity to Clara cell cytotoxicity. III. Morphometric comparison of changes in the epithelial populations of terminal bronchioles and lobar bronchi in mice, hamsters, and rats after parenteral administration of naphthalene.

BACKGROUND: The purpose of this study was to define, in quantitative terms, epithelial alterations produced by the cytochrome P-450-activated Clara cell cytotoxicant, naphthalene, in lobar bronchi and terminal bronchioles of three species with differing sensitivity: mouse, rat, and hamster. EXPERIMENTAL DESIGN: Adult mice, hamsters, and rats were treated intraperitoneally with a single dose of naphthalene ranging from 0 mg/kg up to the approximate LD50. The animals were killed 24 hours postinjection and the changes in airway epithelium characterized by light microscopic morphometry. RESULTS: In mouse, bronchiolar epithelial thickness was significantly elevated by low, but not high, doses; ciliated cell number increased and Clara cell number decreased in a dose-dependent fashion. Vacuolated Clara cell number increased in all treated mice. In rat and hamster, bronchiolar epithelial thickness or cell number did not change. In mice, bronchial epithelial thickness was unchanged except at high doses, but both ciliated and Clara cell number was decreased. In bronchi of rats, epithelial thickness and numbers of nonciliated, ciliated, and basal cells were unchanged. In bronchi of hamsters, both ciliated and nonciliated cell number were decreased. CONCLUSIONS: (a) In mice, naphthalene-induced acute bronchiolar toxicity involves not only Clara cells, but also affects the purported nontarget cell type (ciliated cells). (b) In rats and hamsters, bronchiolar epithelium is insensitive to naphthalene injury. (c) In mice, injury to bronchi occurs at higher doses than in bronchioles and involves both ciliated and nonciliated cells. (d) In rats, bronchi are insensitive. (e) In hamsters, bronchi are more sensitive than bronchioles. This study emphasizes the variability of response by species, airway and epithelial cell type to cytochrome P-450-mediated pulmonary toxicants and the need for precise quantitative methods of defining both cytotoxic and metabolic events.

Animals↗