Effects of ozone on peripheral lung reactivity

1983 ◽  
Vol 55 (3) ◽  
pp. 777-784 ◽  
Author(s):  
A. Gertner ◽  
B. Bromberger-Barnea ◽  
R. Traystman ◽  
H. Menkes

In previous studies, we demonstrated that local exposures to the lung periphery to 0.1 ppm ozone (O3) produce increases in resistance to flow through the collateral system (Rcs) which are prevented by vagotomy, and the local exposures to 1.0 ppm O3 produces increases in Rcs which are only partially mediated by the parasympathetic system. In the present studies, we evaluated the effects of short exposures to O3 on reactions to H2O and histamine in anesthetized male dogs when no residual effects of the O3 exposures could be detected. For this purpose a fiber-optic bronchoscope was wedged in a segmental airway of anesthetized dogs and was used to deliver O3, aerosols of H2O, histamine (1.5 X 10(-4) mg), and atropine (0.1 mg). Measurements of Rcs were used to monitor responses to these agents. Responses to three successive challenges with H2O and with histamine were not different from each other. A 30-min exposure to 0.1 ppm O3 between the first and second challenge did not alter responses to histamine or H2O. However, a 10-min exposure to 1.0 ppm O3 resulted in a significant increase in responses to both H2O and histamine. No correlation was noted between the magnitude of response to O3 and the increase in response to histamine or H2O following O3 exposure. Parasympathetic blockade (atropine or bilateral cervical vagotomy) abolished the increase in response to H2O but not the increase in response to histamine following exposure to 1.0 ppm O3.(ABSTRACT TRUNCATED AT 250 WORDS)

1983 ◽  
Vol 55 (3) ◽  
pp. 770-776 ◽  
Author(s):  
A. Gertner ◽  
B. Bromberger-Barnea ◽  
A. M. Dannenberg ◽  
R. Traystman ◽  
H. Menkes

We studied responses of the lung periphery to short-term exposures of 1.0 ppm ozone (O3). A fiber-optic bronchoscope was wedged in a segmental airway of anesthetized male mongrel dogs and was used to deliver O3 to a small portion of lung. Measurements of resistance through the collateral system (Rcs) were used to monitor responses to O3. During a 30-min exposure to O3, Rcs increased within 2 min (early phase) and then continued to increase throughout the exposure. Bilateral cervical vagotomy or pretreatment with atropine prevented or reduced the response measured at 2 min but not the later increase in Rcs. The later increase was reduced with chlorpheniramine. The administration of indomethacin intravenously and as an aerosol did not alter the response. These results indicate that the early phase of the response to 1.0 ppm ozone in the lung periphery is mediated through the parasympathetic system, and the later phase of the response is related in part to histamine release. We found no evidence that metabolites of the cyclooxygenase pathway played a role in these responses. Furthermore, unlike responses to 0.1 ppm, responses to 1.0 ppm O3 are not characterized by the development of adaptation or tolerance.


1986 ◽  
Vol 61 (2) ◽  
pp. 640-646
Author(s):  
A. N. Freed ◽  
U. A. Scheffel ◽  
L. J. Kelly ◽  
B. Bromberger-Barnea ◽  
H. A. Menkes

Following ozone (O3) exposure, airways reactivity increases. We investigated the possibility that exposure to O3 causes a decrease in pulmonary perfusion, and that this decrease is associated with the increase in reactivity. Perfusion was measured with radiolabeled microspheres. A wedged bronchoscope was used to isolate sublobar segments in the middle and lower lobes of anesthetized dogs. Isolated segments were exposed to either O3 or an elevated alveolar pressure. Although increased alveolar pressure decreased microsphere density, exposure to 1 ppm O3 did not. Collateral system resistance rose significantly following exposure to O3 and to high pressure. These studies do not support the hypothesis that pulmonary perfusion is decreased following O3 exposure and is associated with subsequent increases in reactivity.


1986 ◽  
Vol 60 (6) ◽  
pp. 1954-1959 ◽  
Author(s):  
L. Kelly ◽  
J. Kolbe ◽  
W. Mitzner ◽  
E. W. Spannhake ◽  
B. Bromberger-Barnea ◽  
...  

We investigated the effect of eliminating the bronchial circulation on recovery time from intravenous histamine challenge in canine lung periphery. Results from animals with intact bronchial circulations were compared with a second group in which the left lower lobe was isolated in situ. The pulmonary artery to this lobe was perfused and a bronchoscope was wedged in a small airway, which provided an index of resistance to airflow through the collateral system. The lobe was challenged with intravenous histamine, and the time constant of recovery (tau) from bronchoconstriction was measured. With or without pulmonary blood flow, elimination of the bronchial circulation increased tau 44.4 and 48.5%, respectively. This increase was similar to that found by stopping pulmonary blood flow alone (56.5%). Histamine challenges were also performed in sympathectomized or vagotomized animals with intact bronchial circulations. Neither of these conditions increased tau. We conclude that blood flow through the bronchial circulation affects the recovery time from intravenous histamine challenge in the lung periphery to a degree similar to that of the pulmonary circulation.


1989 ◽  
Vol 67 (5) ◽  
pp. 1727-1733 ◽  
Author(s):  
A. N. Freed

Variation in dry airflow-induced broncho-constriction (AIB) in the canine lung periphery was examined using a wedged bronchoscope technique. Collateral system resistance (Rcs) was measured before and after dry-air challenge. Base-line Rcs was similar throughout the lung periphery, between dogs, and over time. Increasing base-line Rcs was correlated with increasing maximum Rcs 5 min postchallenge (Rcs5), increasing change in Rcs (dRcs5), and decreasing percent change in Rcs above base line (%Rcs5). In contrast to repeated challenge in which base-line Rcs was similar, the magnitude of AIB associated with consecutive challenges with unequal base lines depended on the parameter used to evaluate the response (i.e., Rcs5, dRcs5, or %Rcs5). Peripheral lung resistance then increased to a stimulus specific maximum regardless of base-line Rcs, although data expressed as %Rcs5 or dRcs5 may obscure this observation. Although a change in peripheral lung resistance does not necessarily imply airway narrowing, it is consistent with the idea that changes in Rcs are independent of the collateral system's resting tone.


1984 ◽  
Vol 57 (1) ◽  
pp. 278-283 ◽  
Author(s):  
A. Gertner ◽  
B. Bromberger-Barnea ◽  
R. Traystman ◽  
H. Menkes

We developed a method for maintaining muscarinic tone in a small region of the lung periphery after vagotomy. A fiber-optic bronchoscope was wedged in a segmental airway of anesthetized male mongrel dogs and was used to deliver aerosols of distilled water (0.1 ml), neostigmine (0.022 mg), atropine (0.1 mg), and histamine (1.5 X 10(-4) mg). Measurements of resistance through the collateral system (Rcs) were used to monitor responses to these agents. Rcs increased 37.0 +/- 5.0% (mean +/- SE) after the administration of neostigmine and remained elevated for at least 50 min. The administration of neostigmine in vagotomized animals or in those where the obstructed lung segment was pretreated with atropine resulted in a small increase in Rcs that lasted only 2 min. When bilateral vagotomy was performed 10 min after neostigmine administration Rcs remained elevated for at least another 80 min. However, Rcs returned to baseline when atropine was administered 20 min after vagotomy, but increased when histamine was administered 50 min after atropine. We conclude that after neostigmine administration, parasympathetic tone, dependent on mediators released from the vagus nerve, can be maintained in the lung periphery after vagotomy.


1983 ◽  
Vol 54 (3) ◽  
pp. 640-646 ◽  
Author(s):  
A. Gertner ◽  
B. Bromberger-Barnea ◽  
R. Traystman ◽  
D. Berzon ◽  
H. Menkes

We studied the effects of ozone (O3) and histamine on the lung periphery. A fiber-optic bronchoscope was wedged in a segmental airway of anesthetized male mongrel dogs. Measurements of collateral resistance (Rcoll) were used to monitor responses to O3 and to histamine. Both agents were delivered locally through the bronchoscope. During a 30-min exposure to 0.1 ppm O3, Rcoll increased 31.5 +/- 5.1% within 2 min and then gradually decreased toward control levels in spite of continued exposure to O3. Within 15 min after the exposure ceased, Rcoll had returned to base line. Subsequent exposure to 0.1 ppm O3 did not increase Rcoll. During a 30-min exposure to 1.5 X 10(-6) mg/min histamine aerosol, Rcoll increased 21.5 +/- 5.0% within 2 min and persisted at an elevated level throughout the exposure. Subsequent exposures to histamine produced similar increases in Rcoll. Bilateral cervical vagotomy or pretreatment with atropine aerosol (0.1 mg) prevented responses to O3 but did not prevent responses to histamine. These results indicate that responses to O3, unlike responses to histamine in the lung periphery, are characterized by the rapid development of adaptation and tolerance and are mediated through the vagus nerves.


1985 ◽  
Vol 59 (3) ◽  
pp. 979-984 ◽  
Author(s):  
G. G. Weinmann ◽  
E. W. Spannhake ◽  
B. Bromberger-Barnea ◽  
H. A. Menkes

The present study was undertaken to determine whether beta-adrenoceptors could be physiologically detected in the lung periphery and whether they were under tonic stimulation in the resting state in anesthetized dogs. A fiberoptic bronchoscope was wedged in a sublobar segment of lung in anesthetized male mongrel dogs for measurement of resistance through the collateral system (Rcs). beta-Agents were delivered locally as aerosols through the bronchoscope, and the response was evaluated by changes in Rcs. Distilled water alone produced a mean increase of 8.5 +/- 2.43% (SE) in Rcs at 2 min in six dogs, whereas dl-isoproterenol produced a mean decrease of 8.9 +/- 2.10% (P less than 0.03), thus demonstrating the presence of submaximally stimulated beta-receptors. To test whether the beta-receptors were under tonic stimulation, we compared the effect of aerosolized d- and dl-propranolol in 5 dogs. d-Propranolol that lacks significant beta-blocking activity and dl-propranolol both produced large transient increases in Rcs. However, with d-propranolol, Rcs had returned to base line at 15 min, whereas with dl-propranolol Rcs remained elevated at a mean of 20% above base line for greater than 2 h (P less than 0.01). Local timolol aerosol also produced a sustained increase in Rcs. After pretreatment with reserpine or after bilateral adrenalectomy, both d- and dl-propranolol still produced large transient increases in Rcs, but dl-propranolol no longer produced a sustained increase. Neither isoproterenol nor atropine affected Rcs in the presence of dl-propranolol, nor did pretreatment with atropine affect the response of Rcs to dl-propranolol.


1989 ◽  
Vol 67 (6) ◽  
pp. 2571-2578 ◽  
Author(s):  
A. N. Freed ◽  
K. T. Yiin ◽  
C. E. Stream

Hypertonic aerosol- and dry airflow-induced bronchoconstriction were examined in the canine lung periphery by the use of a wedged bronchoscope technique. Collateral resistance was measured in anesthetized dogs before and after exposure to isotonic and hypertonic aerosols and dry airflow. Hypertonic aerosols produced significantly greater responses than isotonic aerosols, and resistance increased in an exposure-dependent manner. Atropine attenuated responses to these challenges, indicating that aerosol-induced peripheral lung constriction was, in part, muscarinic in origin. Paired hypertonic- and dry airflow-induced constriction exhibited marked differences in magnitude and time course: responses to hypertonic aerosol peaked immediately; dry air-induced responses rose slowly to a maximum 5-min postchallenge. These differences may reflect differences in stimulus strength or differences in the regulatory pathways activated by each challenge. Despite this, a significant correlation exists between aerosol- and dry air-induced responses in the canine lung periphery and suggests that changes in airway fluid osmolality have an important role in the initiation of airflow-induced bronchoconstriction.


1986 ◽  
Vol 60 (5) ◽  
pp. 1554-1560 ◽  
Author(s):  
L. J. Kelly ◽  
W. Mitzner ◽  
E. W. Spannhake ◽  
B. Bromberger-Barnea ◽  
H. A. Menkes

The influence of blood flow through the pulmonary circulation on the time course of recovery of the lung periphery from challenge with three bronchoconstrictive agents was studied in dogs. The rate of perfusion of the left lower lobe was varied between 0 and 300 ml/min. A fiber-optic bronchoscope (OD = 5.5 mm) was wedged in a small airway in the same lobe, and resistance to airflow through the collateral system was continuously monitored. The lung was challenged with histamine aerosol for 1 min, or with intravenous boluses of histamine, acetylcholine, or methacholine. The time constant (tau) of recovery from each of the challenges was measured under the various pulmonary blood flow conditions. The mean tau of the recoveries from histamine was inversely related to the rate of blood flow. However, pulmonary blood flow had no effect on recovery from challenge with acetylcholine or methacholine, two agents metabolized by cholinesterase in lung tissue. From this study we conclude that recovery of the lung periphery from histamine is perfusion dependent, whereas recovery from acetylcholine or methacholine is perfusion independent. This suggests that the rate of blood flow through the pulmonary circulation could play an important role in recovery of the peripheral airways from certain mediators of bronchoconstriction.


1982 ◽  
Vol 53 (3) ◽  
pp. 582-588 ◽  
Author(s):  
A. Gertner ◽  
B. Bromberger ◽  
R. Traystman ◽  
H. Menkes

An animal model for studying responses of the lung periphery to controlled levels of environmental agents has been used to assess the role of histamine in pulmonary responses to cigarette smoke. A fiber-optic bronchoscope was wedged in a peripheral airway of anesthetized dogs. Measurements of collateral resistance (Rcoll) were used to monitor responses to histamine and cigarette smoke. Responses to an aerosol containing histamine (1.5 X 10(-4) mg) and cigarette smoke (420 ml) were measured before and after the administration of an aerosol containing 1.0 mg chlorpheniramine. Prior to the administration of chlorpheniramine, the histamine challenge produced a 75 +/- 26% increase in Rcoll and cigarette smoke produced a 74 +/- 26% increase. Following the administration of chlorpheniramine, the peak responses to histamine and cigarette smoke were reduced by 82 +/- 9 and 61 +/- 8%, respectively. Administration of the same dose of chlorpheniramine prior to challenge with methacholine did not reduce the response to that agent. These results indicate that acute local responses to cigarette smoke in the periphery of the lung are mediated in part through the release of histamine.


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