Biomedical subjects

E W Spannhake

Publications and source records attributed to E W Spannhake.

At least 37 records · Page 2Linked to original sources

PubMed1990

Acute topical steroid administration blocks mast cell increase and the late asthmatic response of the canine peripheral airways.

Previous studies indicated that mast cell number increased after airway exposure to Ascaris suum antigen (Ag). The following two series of experiments were performed to test the hypothesis that this phenomenon may be associated with the Ag-induced late-phase bronchoconstriction (LAR). In the first, two bronchoscopes wedged in airway segments of two contralateral lobes of 16 dogs were used to deliver 0.26, 2.6, or 26 micrograms of Ag to one lobe; the other served as a control. After the observation of a LAR, Ag and control lobes plus one unexposed tissue sample were collected and prepared for histologic examination. The data showed that the incidence, time of onset, and magnitude of the LAR were dose-related. In the second series of experiments, performed in 14 dogs, the tracheal mucosal surface was surgically exposed to allow 80 micrograms of beclomethasone dipropionate to be sprayed on one half while the other half was left untreated. Pledgets saturated with 0.2 microgram of Ag were placed on both sides 1 h later. Then two bronchoscopes were used to pretreat airways of two contralateral lobes to 40 micrograms of either the steroid or the vehicle. One hour later, both airways were exposed to 2.6 micrograms of aerosolized Ag. Of these 14 dogs monitored for peripheral airway responses, seven demonstrated a LAR in the vehicle-treated airway. In all seven dogs, the LAR was absent in the steroid-treated airway even though the cellular profiles of the two airways did not significantly differ. In seven additional dogs, the bronchoscopic procedure was performed as previously described. However, these dogs were killed 1 h after Ag exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed1990

Arachidonic acid metabolism in normal human alveolar macrophages: stimulus specificity for mediator release and phospholipid metabolism, and pharmacologic modulation in vitro and in vivo.

Arachidonic acid (AA) metabolism in normal human alveolar macrophages including phospholipid turnover, stimulus specificity for mediator release including trigger synergy, and the pharmacologic control of the release of AA metabolites was explored. Macrophages labeled overnight with [3H]AA, then activated, released three major AA metabolites, thromboxane B2 (TxB2), leukotriene B4 (LTB4), and 5-hydroxyeicosatetraenoic acid (5-HETE), as characterized by thin layer chromatography, high performance liquid chromatography, and radioimmunoassay. Although all triggers (phorbol myristate acetate [PMA], serum-activated zymosan, and ionophore A23187) resulted in the release of TxB2 and free AA, efficient synthesis of lipoxygenase products, particularly LTB4, required A23187. A23187 was the most effective single agent in producing LTB4 synthesis, was synergistic with PMA in causing LTB4 release, and was associated with significant turnover of phosphatidylcholine and phosphatidylinositol. Incubation of macrophages in vitro with cyclooxygenase inhibitors resulted in an inhibition of the formation of cyclooxygenase products; however, no shunting of metabolites into products of the lipoxygenase pathway was observed. Although overnight incubation of macrophages in vitro with dexamethasone (1 microM) resulted in an inhibition of both the spontaneous and A23187/PMA-triggered release of all AA metabolites, treatment of 5 volunteers with dexamethasone (4 mg po bid x 7 doses, in a single-blind, placebo-controlled, crossover protocol) resulted in no significant inhibition of the release of AA metabolites from macrophages triggered ex vivo. We conclude that activation of normal human alveolar macrophages results in phospholipid turnover (phosphatidylcholine and phosphatidylinositol) and the release of three major AA metabolites (TxB2, LTB4, and 5-HETE); that optimal synthesis of lipoxygenase product requires the presence of a calcium signal (A23187), although PMA can synergize with A23187 in the production of lipoxygenase products; and that glucocorticoids may have a different effect on the release of AA metabolites from alveolar macrophages when administered in vitro versus in vivo.

Arachidonic Acids↗

PubMed1989

Dermal mast cell releasability and end organ responsiveness in atopic and nonatopic dogs.

The Basenji greyhound (BG) has been proposed as a model of atopic disease because of its chronic relapsing atopic dermatitis as well as airway hyperresponsiveness. We attempted to characterize this model further by comparing its skin wheal-and-flare responses to morphine sulfate and histamine with those of control, nonatopic mongrel dogs. We found that BG dogs had significantly smaller skin responses than did the control dogs to all but two concentrations of histamine used. In contrast, BG dogs demonstrated greater skin response to morphine at the three lowest concentrations used but had a significantly smaller skin response at the highest dose of morphine. Skin punch biopsy specimens revealed decreases in histamine content after morphine exposure but no difference in histamine content of the unexposed skin or of morphine-exposed skin for the two groups of dogs. When percent histamine release was compared, however, BG dogs were found to release a significantly greater proportion of histamine in response to morphine than control dogs. Although there was no significant difference in total mast cell counts for the two groups, the BG dogs had significantly fewer formalin-insensitive mast cells in unexposed skin than control dogs. We conclude that skin responses in BG dogs are characterized by decreased end organ responsiveness and greater releasability of mast cells in response to nonimmunologic stimulation.

Animals↗

PubMed1989

Exposure to 1 ppm ozone attenuates the immediate antigenic response of canine peripheral airways.

The effect of oxidant exposure on the immediate airway response to immunologic challenge is controversial. We investigated the response of canine peripheral airways to antigen aerosol, 1-3 h and 24 h after a 5-min exposure to 1 ppm ozone. In dogs that were natively sensitive to Ascaris suum antigen, resistance to flow through the collateral system (Rcs) was measured using the wedged bronchoscope technique. In eight dogs, four sublobar segments of each lung were wedged: two were exposed to ozone for 5 min and two (control) received air with 5% CO2. Ozone caused a mean ( +/- SE) increase in Rcs of 75 +/- 15%, which returned to baseline after 1-3 h. The increase in Rcs elicited by subsequent administration of antigen aerosol (25 microliters, 0.27 mg protein/ml) to the ozone-exposed segments (312.0 +/- 70.6%) was attenuated by 22% compared to controls (398.9 +/- 83.0%; p less than .05). In another series of experiments (n = 5), segments were exposed to ozone or air and challenged with antigen 24 h later and a significant attenuation (38%) of the antigen-induced increase in Rcs was detected compared to controls (178.5 +/- 57.9 vs 289.0 +/- 62.2; p less than .05). Cellular influx of polymorphonuclear leukocytes (PMNs) was not detected by bronchoalveolar lavage (BAL) 1-3 h after ozone, but was found after 24 h (19.8 vs. 4.7%; p less than .01). A significant increase in PMNs was detected in exposed subepithelial tissues 1-3 h after ozone compared to unexposed tissues. Tissue PMNs were not significantly different from unexposed tissues after 24 h, but a shift toward degranulation of mast cells was detected in ozone-exposed tissues at this time. These data suggest that the Rcs response to antigen is attenuated 1-3 h and 24 h after acute (5 min) exposure to 1 ppm ozone, and this effect occurs independently of PMNs in the airways.

Administration, Inhalation↗

PubMed1989

Preexposure to ozone blocks the antigen-induced late asthmatic response of the canine peripheral airways.

The influence of exposure of the airways to ozone on acute allergic responsiveness has been investigated in several species. Little is known, however, about the effect of this environmental pollutant on the late asthmatic response (LAR) in animals in which it is exhibited. The purpose of this study was to evaluate this effect in the canine peripheral airways and to assess the potential role of mast cells in modulating the effect. A series of experiments on seven mongrel dogs demonstrated that the numbers of mast cells at the base of the epithelial region of small subsegmental airways exposed to 1 ppm ozone for 5 min were significantly (p less than .01) increased 3 h following exposure compared to air exposed or nonexposed control airways. In a second series of experiments performed on eight additional mongrel dogs with inherent sensitivity to Ascaris suum antigen, antigen aerosol was administered to the sublobar segment 3 h following ozone preexposure when mast cell numbers were presumed to be increased. These experiments were performed to determine whether ozone preexposure could enhance the late-phase response to antigen by virtue of acutely increasing the number of mast cells available to bind the antigen. Four of the eight dogs tested displayed a late-phase response to antigen following air-sham preexposure. In these four dogs, simultaneous ozone preexposure of a contralateral lobe completely blocked the late-phase response to antigen. These results indicate that the consequences of a single exposure to ozone persist beyond its effects on acute antigen-induced bronchoconstriction and extend to the complex processes involved with the late response. This attenuating effect of ozone is seen under conditions where mast-cell numbers in the airways are increased above baseline levels.

Administration, Inhalation↗

PubMed1988

Rapid increase in mast cell numbers in canine central and peripheral airways.

In preliminary studies of antigen-induced airway inflammation, we noted an apparent increase in peribronchiolar mast cell number. Experiments were thus undertaken to investigate the nature of this migration of mast cells into the central and peripheral airway epithelium and to determine its time course. The tracheae and small airways of 10 anesthetized mongrel dogs were exposed via a bronchoscope to Ascaris suum antigen (Ag), fMet-Leu-Phe (fMLP), ovalbumin (OVA), and isotonic saline (SAL). In the central airways, all stimuli provoked a significant increase (P less than 0.05) in mast cell numbers at the base of the airway epithelium within 3 h. In the peripheral airways, only Ag aerosol stimulated a significant mast cell increase compared with unexposed tissue. In a second series of experiments, the trachea of seven dogs were exposed to 0.026, 0.26, and 2.6 micrograms of Ag. The tissue was collected at 1, 3, 6, and 10 h after exposure. In these experiments, there was a significant mast cell increase seen within 1 h but it was not dose dependent. By 6-10 h after exposure, mast cell counts were not significantly different from the unexposed condition, which is consistent with the idea that some of the cells either degranulated or migrated into the airway lumen. We conclude that mast cell migration is an acute response that can be demonstrated within 1 h of stimulation with Ag. The observation that nonimmunological stimuli may, in some cases, also stimulate mast cell movement affords the possibility that this process represents a generalized response to airway irritation.

Animals↗

PubMed1988

The role of mediators in the response of the canine peripheral lung to 1 ppm ozone.

We tested the hypothesis that the in vivo response of the canine peripheral lung to 1 ppm ozone is mediated, in part, by histamine and cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. Ozone was delivered for 5 min to lobar segments through a wedged bronchoscope and resulted in a mean (+/- 1 SE) increase in collateral system resistance (Rcs) of 220.7 +/- 13.8% immediately after exposure. Four 5-min exposures of ozone to the same segments over a 3-h period yielded reproducible Rcs responses, i.e., tolerance to the exposure regimen was not exhibited. Analyses of bronchoalveolar lavage fluid obtained from the isolated segment 1 min after a single exposure to ozone indicated significant increases, compared with control, in mean concentrations of PGD2 (135.3 +/- 33.3 pg/ml versus 47.8 +/- 16.0; p less than 0.025) and histamine (1.43 +/- 0.19 ng/ml versus 1.18 +/- 0.17; p less than 0.05). Additionally, a molecule that exhibited high reactivity with LTB4 antibody was found in greater concentrations in ozone-exposed segments compared to controls (821.5 +/- 206.7 pg/ml versus 437.5 +/- 78.8; p less than 0.05). In contrast, the concentration of TxB2 was not significantly greater in ozone-exposed segments compared to controls (37.2 +/- 6.6 pg/ml versus 33.7 +/- 10.3; p less than 0.05). Cyclooxygenase inhibition (indomethacin, 5 mg/kg, IV) significantly inhibited the Rcs response by 32% (p less than 0.05) and histamine H1-receptor blockade (chlorpheniramine maleate, 5 mg/kg, IV) reduced the response by 30% (p less than 0.05). However, blockade of thromboxane synthetase (UK-37,248, 3 mg/kg, IV) had no significant effect on the ozone-induced response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

In vivo exposure to ozone causes increased in vitro responses of small airways.

We examined the effects of in vivo exposure to 3 ppm ozone on in vitro reactivity of large and small airways from dogs. No effects in large airways were detected. However, small airways exposed to O3 had larger responses to receptor-mediated stimuli and similar responses to KCl plus phorbol ester. These results suggest that small airways are more vulnerable to O3 inhalation than are large airways and that receptor-mediated pathways reflect that sensitivity. Another possible explanation is that O3 exposure prevents the epithelium from playing its normal dampening role in responses to contractile agonists.

Animals↗

PubMed1988

The role of cyclooxygenase and lipoxygenase mediators in oxidant-induced lung injury.

Infusion of the oxidant lipid peroxide tert-butyl hydroperoxide (t-bu-OOH) causes pulmonary vasoconstriction and increases vascular permeability in isolated perfused rabbit lungs. We have previously shown that t-bu-OOH stimulates arachidonic acid metabolism, increasing the synthesis of the cyclooxygenase products. The current experiments were designed to determine the role that cyclooxygenase- and lipoxygenase-derived mediators play in the lung injury caused by t-bu-OOH. In the present experiments, we found that t-bu-OOH not only increased the synthesis of the cyclooxygenase-derived products thromboxane and prostacyclin but also increased the synthesis of the lipoxygenase-derived products leukotrienes B4, C4, D4, and E4. To determine the role that these arachidonic acid metabolites play in the increase in pressure and vascular permeability caused by t-bu-OOH, we studied the effect that inhibitors of arachidonic acid metabolism or a leukotriene receptor blocker had on the pulmonary edema. We compared an uninjured control group with 4 groups of lungs given t-bu-OOH: a t-bu-OOH control group; a group pretreated with the cyclooxygenase inhibitor indomethacin (14 microM); a group pretreated with an analogue of arachidonic acid, 5-, 8-, 11-, 14-eicosatetraynoic acid (ETYA) (100 microM), that inhibits both the cyclooxygenase and lipoxygenase pathways; and a group pretreated with the leukotriene receptor antagonist FPL 55712 (38 microM). To produce lung injury, t-bu-OOH (300 microM) was infused throughout the first minute of 4 successive 10-min periods.(ABSTRACT TRUNCATED AT 250 WORDS)

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1987

Thromboxane contributes to the immediate antigenic response of canine peripheral airways.

The actions of specific humoral mediators in the immediate response of the canine peripheral airways to antigen challenge are not well understood. Using a method which allows localized exposure of the peripheral lung to antigen, we investigated the role of locally released thromboxane A2 (TxA2) in the immediate response of collateral airways to aerosolized antigen. In dogs with native sensitivity to Ascaris suum antigen, resistance to flow through the collateral system (Rcs) was measured using a wedged bronchoscope technique. Local administration of antigen aerosol (25 microliters, 1:10,000 dilution) produced a gradual increase in Rcs which reached a maximum of 365% of base line in 4-8 min. Analysis of bronchoalveolar lavage fluid obtained from the exposed segment at the peak of the response demonstrated significantly more TxB2 compared with control lavage samples (41.8 +/- 7.8 pg/ml vs. 27.9 +/- 8.3; P less than 0.025). After inhibition of thromboxane synthase with UK-37,248 (3 mg/kg iv) or OKY-046 (5 mg/kg iv), the increase in Rcs was significantly reduced at 40 s (P less than 0.001) and 2 min (P less than 0.01) after antigen delivery, and the maximal increase was attenuated by 41% (P less than 0.005). In contrast, the magnitude and time course of the airway response to aerosols of a stable thromboxane analog (U-46619) were not affected by blockade. Despite a similar attenuation (42%) of the maximal increase in Rcs by sodium meclofenamate (3 mg/kg iv), this cyclooxygenase inhibitor had no effect on the time course of the antigenic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1987

Hypocapnia-induced constriction of the canine peripheral airways exhibits tachyphylaxis.

Hypocapnia-induced constriction of peripheral airways may be important in regulating the distribution of ventilation in pathological conditions. We studied the response of the peripheral lung to hypocapnia in anesthetized, paralyzed, mechanically ventilated dogs using the wedged bronchoscope technique to measure resistance of the collateral system (Rcs). A 5-min hypocapnic challenge produced a 161 +/- 19% (mean +/- SE) increase in Rcs. The magnitude of this response was not diminished with repeated challenge or by atropine sulfate (1 mg base/kg iv), chlorpheniramine maleate (5 mg base/kg iv), or indomethacin (5 mg/kg iv). The response was reduced by 75% by isoproterenol (5 micrograms/kg iv) (P less than 0.01) and reduced by 80% by nifedipine (20 micrograms/kg iv) (P less than 0.05). During 30-min exposure to hypocapnia the maximum constrictor response occurred at 4-5 min, after which the response attenuated to approximately 50% of the maximum response (mean = 53%, range 34-69%). Further 30-min challenges with hypocapnia resulted in significantly decreased peak responses, the third response being 50% of the first (P less than 0.001). The inability of indomethacin or propranolol to affect the tachyphylaxis or attenuation of the response suggests that neither cyclooxygenase products nor beta-adrenergic activity was involved. Hence, hypocapnia caused a prompt and marked constrictor response in the peripheral lung not associated with cholinergic mechanisms or those involving histamine H1-receptors or prostaglandins. With prolonged exposure to hypocapnia there was gradual attentuation of the constrictor response with continued exposure and tachyphylaxis to repeated exposure both of which would tend to diminish any compensatory effect of hypocapnic airway constriction on the distribution of ventilation.

Airway Resistance↗

PubMed1986

Cyclooxygenase mediated airway response to leukotriene D4 in the cat.

The effects of leukotriene D4 (LTD4) on pulmonary mechanics were investigated in anesthetized, paralyzed cats under conditions of controlled ventilation. Intravenous injections of LTD4 in doses of 3, 10, and 30 micrograms caused significant increases in transpulmonary pressure (PTP) and lung resistance (RL) while decreasing dynamic compliance (Cdyn). LTD4 also increased systemic arterial pressure (PAo). The changes in PTP, RL, and Cdyn in response to LTD4 were blocked by sodium meclofenamate, a cyclooxygenase inhibitor. However, there was no significant change in the increase in PAo following cyclooxygenase blockade. U 46619, a thromboxane mimic, was 30 to 100 times more potent than LTD4 in increasing PTP, RL and decreasing Cdyn in the cat. These data show that LTD4 has significant smooth muscle constrictor activity in central airways as well as peripheral portions of the feline lung. In addition, these data suggest that in the cat the actions of intravenously administered LTD4 on lung mechanics are mediated by release of cyclooxygenase products while the systemic pressor effects are not dependent upon the integrity of the cyclooxygenase pathway.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1986

Pulmonary blood flow affects recovery from constriction in dog lung periphery.

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.

Acetylcholine↗

PubMed1986

Bronchial blood flow affects recovery from constriction in dog lung periphery.

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.

Animals↗

PubMed1986

Central role of cyclooxygenase in the response of canine peripheral airways to antigen.

We studied the effects of antigen aerosol challenge on the airways of the canine peripheral lung and examined the roles of cyclooxygenase products, histamine, and cholinergic activity in the responses. One-minute deliveries of 1:10,000 or 1:100,000 concentrations of Ascaris suum antigen aerosol through a wedged bronchoscope resulted in mean maximal increases in collateral system resistance (Rcs) of 415 and 177%, respectively, after 4-8 min. Repeated antigen challenge (1:100,000) resulted in significantly decreased responsiveness to antigen after the initial exposure (P less than 0.005). Bronchoalveolar lavage fluid obtained from the isolated, challenged segment had a significant increase in mean (+/- SE) prostaglandin D2 (PGD2) concentration vs. control (222.0 +/- 65.3 vs. 72.7 +/- 19.5 pg/ml; P less than 0.05); histamine concentrations were variable and not significantly different (4.1 +/- 2.6 vs. 1.2 +/- 0.2 ng/ml; P greater than 0.05). In nine experiments, cyclooxygenase inhibition significantly attenuated the antigen-induced increase in Rcs by 53.4% (P less than 0.001), and the concentration of PGD2 in lavage fluid was reduced by 96.0% (P less than 0.01). Blockade of histamine H1-receptors (n = 8) or cholinergic receptors (n = 7) did not significantly affect the airway response (P greater than 0.05). These data indicate that the canine peripheral lung responds in a dose-dependent manner to antigen aerosol challenge and exhibits characteristics of antigen tachyphylaxis. Results also suggest that cyclooxygenase products play a central role in the acute bronchoconstrictive response of the lung periphery.

Aerosols↗

PubMed1986

Leukotriene D4 increases pulmonary vascular permeability and pressure by different mechanisms in the rabbit.

We designed experiments to define the effects of leukotriene D4 (LTD4) in the rabbit lung and to determine whether or not these effects were due to the synthesis of cyclooxygenase products. Infusion of LTD4 (0.01, 0.03, and 0.10 microgram) into the rabbit pulmonary vasculature caused a dose-related increase in pulmonary arterial pressure and tracheal pressure. Pretreatment with FPL 55712 (38 microM), a leukotriene receptor antagonist, or indomethacin (10 micrograms/ml of perfusate) completely prevented the increase in tracheal and pulmonary arterial pressure. We also studied the effect of LTD4 on pulmonary vascular permeability by measuring lung weight gain at 4 levels of left atrial pressures (0, 5, 10, and 15 mmHg). Leukotriene D4 increased lung weight gain at all levels of left atrial pressure compared with that in the control group. Pretreatment with FPL 55712 completely inhibited the increase in vascular permeability caused by LTD4. Although pretreatment with indomethacin blocked the increase in tracheal and vascular pressure caused by LTD4, it did not prevent the increase in vascular permeability. We conclude that in the rabbit, LTD4 increases tracheal pressure, pulmonary arterial pressure, and pulmonary vascular permeability. Leukotriene D4 increases tracheal and pulmonary arterial pressure by stimulating the synthesis of cyclooxygenase products, and it increases vascular permeability through a mechanism that does not require the synthesis of cyclooxygenase products.

Animals↗

PubMed1985

Influence of chronic antigen exposure on the metabolism of PGH2 by microsomal preparations of airway and parenchymal tissues in the sheep.

The effects of repeated antigen exposure on the synthesis of mediators by lung tissues are not well understood. To investigate the influence of antigen challenge on the synthesis of prostaglandins by central airway and peripheral lung tissues, fourteen sensitive sheep underwent biweekly exposure to aerosolized Ascaris suum antigen (7) or saline (7). Following the fifth exposure, microsomal and high speed supernatant fractions were prepared from trachealis muscle and lung parenchyma. Synthesis of thromboxane (TX) A2, prostaglandin (PG) D2 and PGI2 from the PG endoperoxide intermediate, PGH2, was assayed over a range of substrate concentrations from 3-200 microM. Synthesis of PGI2 by trachealis microsomes was approximately 5-fold greater than that of TXA2. PGI2 and TXA2 production was identical in tracheal preparations from Ascaris- and saline-exposed animals. In parenchymal tissues, where TXA2 production predominated over PGI2 by 9-fold, preparations from Ascaris-exposed animals synthesized 50% more TXA2 than controls at PGH2 concentrations of 25 microM and above, whereas synthesis of PGI2 and PGD2 were similar in preparations from both groups of animals. The density of pulmonary mast cells was decreased by 21% in the Ascaris group, whereas polymorphonuclear leukocyte density was unchanged. These results demonstrate the differential synthesis of TXA2 and PGI2 in central airways and peripheral lung regions of the sheep. They further indicate that repeated exposure of the airways to antigen selectively enhances TXA2 synthesis in the lung periphery of sensitized animals. The site of this increased enzymatic activity, whether in resident cells or newly-infiltrated cells, has not been determined.

Animals↗

PubMed1985

Tonic beta-sympathetic activity in the lung periphery in anesthetized dogs.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗