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Biomedical subjects

A Wanner

Publications and source records attributed to A Wanner.

At least 127 records · Page 7Linked to original sources
PubMed1985

Vascular and airway effects of endogenous cyclooxygenase products during lung inflation.

The influence of lung inflation on lung elasticity and pulmonary resistance (RL) and on pulmonary and bronchial hemodynamics was examined in five anesthetized, mechanically ventilated adult sheep before and after treatment with the cyclooxygenase inhibitor indomethacin (2 mg/kg). Lung inflation was accomplished by increasing levels of positive end-expiratory pressure (PEEP). Measurements of pulmonary vascular resistance (PVR), bronchial blood flow (Qbr), and RL were obtained with a Swan-Ganz catheter, with an electromagnetic flow probe placed around the carinal artery, and by relating airflow to transpulmonary pressure (Ptp), respectively. Before indomethacin, increasing PEEP from 5 to 15 cmH2O increased mean lung volume (VL) to 135% (P less than 0.01), Ptp to 165% (P less than 0.005), and PVR to 132% (P less than 0.05) of base line and decreased mean Qbr (normalized for cardiac output) to 53% (P less than 0.05) of base line. Mean RL showed a tendency to decrease with a mean value of 67% of base line at 15 cmH2O PEEP. After indomethacin the corresponding values were 121% for VL, 155% for Ptp, 124% for PVR, 35% for Qbr, and 31% for RL. The PEEP-dependent changes were not different before and after indomethacin except for mean VL, which increased less (P less than 0.05) after indomethacin. The failure of indomethacin to modify PEEP-induced changes in RL, PVR, and Qbr was also present when these parameters were expressed as a function of Ptp. These findings suggest that the cyclooxygenase products elaborated during lung inflation reduce lung elasticity but fail to influence airflow resistance and pulmonary and bronchial hemodynamics.

Animals↗
PubMed1985

Effects of leukotriene D4 on mucociliary and respiratory function in allergic and nonallergic sheep.

We determined the effect of aerosol challenge with leukotriene D4 (LTD4) on specific lung resistance (sRL) and tracheal mucous velocity (TMV) in conscious sheep with (allergic) and without (nonallergic) Ascaris suum hypersensitivity. In allergic sheep LTD4 in concentrations of 50, 100, and 150 micrograms/ml produced dose-dependent increases in mean sRL by 44 (P = NS), 154 (P less than 0.05), and 233% (P less than 0.05), respectively. The increase in sRL produced by 150 micrograms/ml LTD4 was prevented by FPL 55712, an antagonist of slow-reacting substance of anaphylaxis. In nonallergic sheep 150 micrograms/ml LTD4 failed to elicit a significant change in sRL. In contrast to the changes in airway mechanics, concentrations of LTD4 as low as 25 micrograms/ml produced significant decreases in TMV in allergic sheep. The maximum decrease in TMV at this dose occurred 2 h after challenge; with larger doses of LTD4 (100 and 150 micrograms/ml) the maximum effect was observed 3 h after challenge. Furthermore, 150 micrograms/ml LTD4 reduced TMV in nonallergic sheep (mean decrease 43%, P less than 0.05). FPL 55712 only had a minor effect on the LTD4-induced decreases in TMV. We conclude that allergic sheep exhibit greater airway responsiveness to inhaled LTD4 than nonallergic sheep but that this difference is not evident for the concomitant changes in mucociliary transport. This suggests that the allergic state is associated with an increased responsiveness to LTD4 in tissues controlling airway caliber but not in those contributing to mucociliary function.

Aerosols↗
PubMed1985

Bronchial circulation in asthma.

Whereas the anatomical changes of the bronchial circulation in response to a wide variety of congenital and acquired cardiopulmonary diseases have been well described, little is known about its functional response. There is growing evidence that the bronchial circulation plays a major role in the pathophysiology of hyperreactive airway disease. The bronchial vascular system appears to be involved in mediator transport to and from target tissues in the airway wall, in the development of airway wall edema which may contribute to airflow obstruction, and in heat and water exchange in the tracheobronchial tree. Although our current understanding of these functions is rather sketchy, enough is known to outline the contributions of the bronchial, i.e. the systemic circulation to the mechanisms of bronchial asthma.

Animals↗
PubMed1985

Direct and indirect effects of leukotriene D4 on the pulmonary and systemic circulations.

We investigated direct (vascular leukotriene receptor stimulation) and indirect (generation of cyclooxygenase metabolites) hemodynamic effects of leukotriene D4 (LTD4) in 6 conscious sheep. Pulmonary artery, pulmonary arterial wedge and systemic arterial pressures, and cardiac output were measured. From these parameters, pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were calculated before and immediately after a rapid injection of LTD4 into the pulmonary artery. Injection of 0.1 micrograms/kg of LTD4 increased mean PVR to 421% of baseline (p less than 0.001). It produced a biphasic effect on SVR that, after an initial decrease of 18% (p less than 0.05), increased to 143% of baseline (p less than 0.05). Both PVR and SVR returned to baseline within 10 min. The same results were obtained when the dose of LTD4 was increased to 0.5 micrograms/kg. Dose-response curves with increasing doses of LTD4 )0.025 micrograms/kg to 0.5 micrograms/kg) revealed that the optimal dosage for maximal effect was 0.1 micrograms/kg. The effects of LTD4 (0.1 micrograms/kg) on the pulmonary circulation were completely blocked by the SRS-A antagonist, FPL-57231, as well as by indomethacin. In the systemic circulation, FPL-57231 blocked the biphasic effects of LTD4 on SVR, whereas indomethacin prevented the initial decrease without attenuating the subsequent increase in mean SVR (135% of baseline, p less than 0.05). We conclude that there are direct and indirect hemodynamic effects of LTD4: the systemic vasoconstrictor response is directly related to vascular leukotriene receptor stimulation, whereas activation of cyclooxygenase pathway products is responsible for the pulmonary vasoconstrictor and systemic depressor responses.

Animals↗
PubMed1985

Variability of airway responsiveness to histamine aerosol in normal subjects. Role of deposition.

The purpose of this investigation was to determine if the variability of bronchial responsiveness to inhaled histamine in normal subjects is related to the total dose of histamine deposited in the airways. To test this possibility, we used a new method of histamine challenge that permits calculating the histamine mass deposited in the airways in an attempt to correlate it with the magnitude of the response. Using a standardized breath-holding maneuver, 10 healthy nonsmokers and 10 healthy smokers with normal spirometry inhaled an aerosol generated from a solution containing a fixed ratio of histamine and a small quantity of hematoporphyrin serving as a fluorescent tracer. The mass of histamine deposited was calculated from the measured fluorescence of the inspired and expired aerosol. Forced expiratory volume in one second (FEV1) was measured before and 10 min after inhalation challenge. There was a negative correlation between percent decrease in FEV1 (delta FEV1) and histamine mass deposited in the nonsmokers (r = -0.83, p less than 0.005) and smokers (r = -0.82, p less than 0.005) without a difference between the 2 slopes. The range of delta FEV1 was 7 to 33% and of histamine mass deposited, 0.02 to 0.18 mg in the nonsmokers. The respective values in the smokers were 2 to 30% and 0.02 to 0.17 mg. In 6 subjects in whom dose-response curves were obtained, the mean deposited histamine mass required to decrease the FEV1 by 10% was 0.11 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

A review of the effects of cigarette smoke on airway mucosal function.

This review examines the effects of tobacco smoke on the production and clearance of lower airway secretions, in healthy smokers and smokers with chronic bronchitis. Cigarette smoke shows to have a profound effect on airway mucociliary function, producing structural and functional changes in the mucosa.

Bronchitis↗
PubMed1983

Histamine receptor blocking effects of cimetidine in the airways.

We investigated the modification of histamine-induced bronchoconstriction by the H2-antagonist cimetidine in conscious sheep. One hundred breaths of 5% histamine aerosol increased mean (SD) pulmonary resistance (RL) by 5.6 (1.4) cmH2O/l/sec. This increase in RL was completely blocked by intravenous clemastine (0.5 mg), a specific H1-antagonist, indicating that the histamine-induced bronchoconstriction was mediated by H1-receptors. Intravenous cimetidine caused a dose-dependent enhancement of the histamine response between 1 and 1000 mg with a mean peak delta RL of 15.3 (5) cmH2O/l/sec (p less than 0.05) at the 1000 mg dose, while it blocked the histamine response at a dose of 2400 mg [delta RL = 1.9 (2) cmH2O/l/sec, p = NS]. This paradoxic effect was not related to an anticholinergic mechanism as intravenous cimetidine (2400 mg) failed to block carbachol-induced (25 breaths of 1% solution) bronchoconstriction. We conclude that in the ovine airway, cimetidine is a selective H2-histamine receptor blocker at lower tissue concentrations, and a combined H2- and H1-histamine receptor blocker at high tissue concentrations.

Airway Resistance↗
PubMed1983

Allergic mucociliary dysfunction.

This brief summary of several studies relating to allergic mucociliary dysfunction suggests that (1) mucociliary transport in the lower airways (and possibly in the nose) is impaired in subjects with allergic airway disease, (2) acute antigen challenge causes a further impairment of mucociliary transport that is related to chemical mediators, and (3) the elaboration of abnormal respiratory secretions is, at least in part, responsible for acute allergic mucociliary dysfunction. It is apparent from the currently available information that some of the in vivo and in vitro studies carried out in patients with allergic asthma would have to be applied to patients with allergic rhinitis. With respect to the management of patients with allergic rhinitis and asthma, the use of antiallergic agents such as cromolyn sodium or specific mediator antagonists (as they become available) seems to be justified when considering the important role of mucociliary dysfunction in the manifestations of allergic airway disease.

Animals↗
PubMed1983

Effects of chemical mediators of anaphylaxis on ciliary function.

We assessed the effects of selected chemical mediators of anaphylaxis on CBF in vitro. Ciliated epithelial cells were obtained from the trachea of conscious sheep with a cytology brush and suspended in a perfusion chamber containing KH. Ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of CBF. Prostaglandin E1 (10(-8) M to 10(-6) M), prostaglandin E2 (10(-10) M to 10(-6) M), and leukotriene-C4 (10(-8) M) increased CBF between 7% and 33%. Histamine caused ciliostimulation only at the relatively high concentrations above 10(-5) M (7% increase in CBF), whereas prostaglandin F2 alpha (10(-10) M and 10(-6) M) was without effect. In no preparation was ciliary discoordination observed. These findings indicate that several chemical mediators of anaphylaxis stimulate CBF and that the previously described impairment of mucociliary transport in stable allergic asthma or antigen-induced bronchoconstriction is probably not caused by a primary alteration of ciliary function.

Alprostadil↗
PubMed1983

Inhibition of pulmonary macrophage function by airway mucus.

As a model for the interaction between macrophages and mucus in the tracheobronchial tree, we incubated sheep alveolar macrophages in vitro with and without airway mucus from the same animal and tested their phagocytic function and rates of general protein synthesis. Airway mucus was obtained by tracheal suction after previous subcutaneous injection of the sheep with pilocarpine (0.5 mg/kg) and subsequently diluted. Pulmonary macrophages were obtained by saline lavage through a balloon-tipped fiber-optic bronchoscope. In incubated attached macrophages, phenylalanine incorporation into protein was inhibited 51% by mucus (P less than 0.001). Phagocytosis of 1.09-microns latex particles was inhibited 75% by mucus at nonsaturating levels of particles (P less than 0.001) and by 47% at saturating levels of particles (P less than 0.001). Inhibitory activity for protein synthesis and phagocytosis was retained in the 104,000 g supernatant fraction of whole mucus (sol), while the gel fraction inhibited phagocytosis only. This difference did not appear to be related to physical factors. We conclude that diluted airway mucus interferes with pulmonary macrophage function as assessed by rates of general protein synthesis and phagocytosis.

Animals↗
PubMed1983

Duration of mucociliary dysfunction following antigen challenge.

Antigen-induced bronchospasm is associated with an impairment of airway mucociliary clearance, but the duration of this defect has not been examined. In the present study, we determined the time course of mucociliary dysfunction following inhalation challenge with Ascaris suum extract in conscious sheep with hypersensitivity to this antigen. Tracheal mucous velocity (TMV) as an index of mucociliary function, pulmonary resistance (RL), and arterial oxygen tension (Pao2) were measured prior to, immediately after, and serially for 8 h after inhalation challenge. TMV and Pao2 were then measured periodically for at least 2 wk. Immediately after A. suum challenge, mean RL increased to 264% of base line (P less than 0.05), and mean Pao2 decreased to 61% of base line (P less than 0.05). By 2 h postchallenge, mean RL and Pao2 had returned to base line but mean TMV had fallen to 61% of base line (P less than 0.05). Mean TMV reached a minimum of 35% of base line after 5 h (P less than 0.05) and remained significantly depressed between 37% and 54% of base line for 7 days; by day 9, mean TMV had returned to base line. Inhalation challenge with a control antigen (ragweed) failed to alter mean TMV, RL, and Pao2 during the first 8 h and TMV and Pao2 at any time throughout the 2-wk observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Antigen stimulates glycoprotein secretion and alters ion fluxes in sheep trachea.

We studied the effects of in vitro challenge with specific antigen (Ascaris suum antigen) on glycoprotein secretion and ion fluxes in tracheal tissues from allergic sheep. We mounted tissues in Perspex chambers and measured secretion of 35S- and 3H-labeled glycoproteins and fluxes of Cl- and Na+. In tissues from allergic sheep, A. suum antigen (25 micrograms protein X ml-1) increased glycoprotein secretion. A. suum antigen initially reversed net Cl- flux, causing net absorption of Cl- and of Na+. This was followed 15-30 min later by net secretion of Cl- and of Na+. Pretreatment of tissues with cromolyn (10(-4) M) greatly reduced the effects of A. suum antigen but did not abolish them. The cromolyn-resistant effects were nonspecific, because they were similar to those of in vitro challenges with nonspecific proteins, ovalbumin and ragweed in allergic sheep, and A. suum antigen in nonallergic sheep. We conclude that challenge with A. suum antigen results in mucus hypersecretion in airways of allergic sheep, by both specific and smaller nonspecific effects. Specific effects (cromolyn sensitive) are produced by mediators which are released from airway cells in response to A. suum challenge.

Animals↗
PubMed1983

Variability of hypoxic pulmonary vasoconstriction in sheep. Role of prostaglandins.

In a minority of conscious sheep, the hypoxic pulmonary vasoconstrictor response is blunted ("nonresponders"). The purpose of this investigation was to determine if this blunted response is related to an increased activity of H2-histamine receptors, beta-adrenergic receptors, or the generation of inhibitory prostaglandins. We measured pulmonary arterial pressure, pulmonary arterial wedge pressure, and pulmonary blood flow for the calculation of pulmonary vascular resistance (PVR) in 5 "nonresponders" and 5 sheep with a typical hypoxic pulmonary vasoconstrictor response ("responders") while breathing room air and 13% O2 (balance, N2). Arterial oxygen tension (PaO2) was also determined as a measure of the severity of hypoxia. During hypoxia, mean PVR increased by 6% (p = NS) in the "nonresponders" (PaO2, 49 +/- 4 mmHg), and by 70% (p less than 0.01) in the "responders" (mean PaO2, 46 +/- 4 mmHg). Metiamide (H2-blocker) and propranolol (beta-adrenergic blocker) pretreatments did not restore the hypoxic pulmonary vascular response in the "nonresponders," whereas pretreatment with indomethacin (prostaglandin synthetase inhibitor) caused mean PVR to increase by 48% (p less than 0.01) during hypoxia, indicating a partial restoration of hypoxic pulmonary vasoconstriction. In the "responders," the hypoxic pulmonary vascular response was not potentiated by indomethacin pretreatment (68% increase in mean PVR). We conclude that some sheep exhibit a blunted hypoxic pulmonary vasoconstrictor response caused by enhanced production of inhibitory prostaglandins.

Animals↗
PubMed1983

Immediate cardiovascular effects of tension pneumothorax.

We studied the immediate cardiovascular effects of unilateral tension pneumothorax in sheep, a species with an intact mediastinal pleura similar to that in humans. Adult animals were restrained in the prone position and studied in the conscious state to permit spontaneous respiratory adjustments. We measured pressures in the ipsilateral pleural space (Ppli), contralateral pleural space (Pplc), esophagus (Pes), pulmonary artery (Ppa), superior vena cava (Pcv), carotid artery (Ps), as well as thermodilution cardiac output (CO) and heart rate (HR). Acute unilateral pneumothorax of 0, 10, and 20 cmH2O tension produced no significant changes in mean Ps, Pcv, and CO at any level of tension, but it did produce a marked increase in HR at 10 and 20 cmH2O tension (p less than 0.05). Similar observations were made with unilateral pneumothorax of 15 cmH2O for 30 min. These results suggested that tension was transmitted incompletely to the mediastinum and contralateral hemithorax. This was confirmed by an increase from baseline of mean (+/- SE) end-expiratory Pes by 6.6 +/- 4.9 cmH2O and Pplc by 6.7 +/- 6.0 cmH2O, for an increase in Ppli by 20.5 +/- 4.0 cmH2O. The respiratory intrathoracic pressure fluctuations were accentuated with mean increases of 211, 78, and 117% in the ipsilateral pleural space, esophagus, and contralateral pleural space, respectively (p less than 0.05). When the increase in respiratory intrathoracic pressure fluctuations was prevented by artificial hyperventilation, CO decreased. We conclude that unilateral tension pneumothorax does not directly lower CO and Ps because of (1) incomplete transmission of the ipsilateral pleural pressure to the mediastinum and contralateral hemithorax, (2) marked respiratory intrathoracic pressure swings, and (3) compensatory tachycardia.

Animals↗
PubMed1983

Allergic mucociliary dysfunction.

Allergic rhinitis is typically associated with excessive nasal secretions and morphologic changes of the nasal mucosa; however, an impairment of mucociliary transport, the ultimate expression of mucociliary function, has so far not been clearly demonstrated. Tracheal mucociliary transport rates are decreased in patients with allergic asthma, and inhalation challenge with antigen causes a further impairment that appears to be related to the liberation of chemical mediators, notably slow reacting substance of anaphylaxis. Physiologic studies of mucociliary function in the nose similar to those that have been reported for the lower airways will be required to assess the role of mucociliary dysfunction in allergic rhinitis.

Antigens↗