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Biomedical subjects

A Gertner

Publications and source records attributed to A Gertner.

17 recordsLinked to original sources

Interstitial fibrosis and collateral ventilation.

Interstitial fibrosis may increase resistance to collateral flow (Rcoll) because of decreased lung volume and destruction of collateral channels or it may decrease Rcoll because of emphysematous changes around fibrotic regions. In addition, if interstitial fibrosis involves a small region of lung periphery, interdependence from surrounding unaffected lung should produce relatively large changes in volume of the fibrotic region during lung inflation. We studied the effects of interstitial fibrosis on collateral airflow by measuring Rcoll at functional residual capacity (FRC) in nine mongrel dogs before and 28 days after the local instillation of bleomycin into selected lung segments. In six of these dogs Rcoll was also measured at a higher lung volume (transpulmonary pressure = 12 cmH2O above FRC pressure). Rcoll increased in fibrotic lung segments following local treatment with bleomycin. With lung inflation (high transpulmonary pressure) Rcoll fell a similar proportion in fibrotic and nonfibrotic lung regions. These observations suggest that collateral resistance increases in fibrotic segments because lung volume decreases or because collateral pathways are involved directly in the fibrotic process. Compensatory increases in collateral communications do not occur. In addition, pulmonary interdependence does not cause disproportionate increases in volume and decreases in Rcoll of the fibrotic region during lung inflation.

Airway Resistance↗

Maintenance of muscarinic tone after vagotomy in the lung periphery.

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.

Acetylcholine↗

Local vagal responses in the lung periphery.

In previous work we studied responses to ozone (O3) in the lung periphery of anesthetized male mongrel dogs. O3 (0.1 ppm) delivered locally to the lung periphery through a bronchoscope wedged in a segmental airway increased collateral resistance (Rcs) 31.5 +/- 5%. Bilateral cervical vagotomy or pretreatment with atropine aerosol prevented these responses to O3. In the present study we asked two questions. First, is the vagus necessary for responses to 0.1 ppm O3 because it maintains base-line tone? Second, are physiological responses to O3 administered through a bronchoscope localized to the challenged region? To answer the first question, we increased base-line Rcs (38.4 +/- 11.8%) by administering an acetylcholinesterase inhibitor, neostigmine (aerosol), through the bronchoscope. Following neostigmine, O3 exposure increased Rcs (55.8 +/- 18.4%) only if the vagi were intact. To answer the second question, we introduced two bronchoscopes simultaneously into different regions of the lung. When O3 was delivered through one bronchoscope, responses were detected only in the exposed region. However, when the whole left lung was exposed to O3, the responses were also detected in the right lung, but only when the vagi were intact. We conclude that the lung has the capacity to respond to localized oxidant insult with vagally mediated responses limited to the region that is challenged. However, when a larger area is exposed, vagally mediated responses become generalized and affect both lungs.

Animals↗

Responses of the lung periphery to ozone and histamine.

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.

Anesthesia, General↗

Responses of the lung periphery to 1.0 ppm ozone.

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.

Animals↗

Effects of ozone on peripheral lung reactivity.

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)

Animals↗

Histamine and pulmonary responses to cigarette smoke in periphery of the lung.

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.

Animals↗

Airway reactivity in the periphery of the lung in mongrel dogs. Male and female differences.

The present study was designed to compare acute responses of the lung periphery to locally administered histamine in male and female dogs. A fiberoptic bronchoscope was wedged in peripheral airways of anesthetized dogs. Increasing doses of histamine were directed through the bronchoscope. Measurements of collateral resistance (Rcoll) were used to monitor responses to histamine and lung inflation. Baseline measurements of Rcoll were similar for both sexes. The males responded to histamine with greater increases in Rcoll than the females did. After doses of histamine (1.5 x 10(-6) mg for males and 1.5 x 10(-4) mg for females), which produced similar increases in Rcoll, the effects of lung inflation and the time course of the responses were similar for the two sexes. We conclude that male dogs exhibit greater reactivity to histamine than female dogs do. If these results apply to humans, it is possible that increased reactivity in the lung periphery contributes to the development of chronic obstructive pulmonary disease in males.

Airway Resistance↗