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Biomedical subjects

A Wanner

Publications and source records attributed to A Wanner.

197 records · Page 11Linked to original sources
PubMedDate not supplied

The effect of systemic hydration on normal and impaired mucociliary function.

Whether systemic hydration enhances the clearance of lower airway secretions in normal lungs and in lungs during antigen-induced bronchial obstruction was studied. In five conscious allergic sheep, tracheal mucus velocity (TMV) as an index of lower airway mucociliary clearance was measured before and serially for 60 minutes following intravenous infusion of 5% dextrose solution at volumes ranging from 5 to 35 ml/kg. None of these fluid regimens had a significant effect on TMV, although there was a tendency toward a slowing of TMV at the higher volumes of 25 and 35 ml/kg. After producing an acute allergic airway response by inhalation challenge with specific antigen, there was a decrease in mean TMV by 27% and 15% before sham infusion and infusion of 35 ml/kg of dextrose solution, respectively. During the subsequent 60-minute observation period, mucociliary transport was further impaired by dextrose infusion, with mean TMV being lower after dextrose infusion than after sham infusion at all times of measurement (P less than 0.05). The lowest value was reached 30 minutes after dextrose infusion (45% of control). It was concluded that systemic hydration does not significantly alter airway mucociliary transport in the normal state but further impairs mucociliary transport during allergic mucociliary dysfunction. This raises questions regarding the therapeutic role of systemic hydration in the treatment of children and adults who have bronchial asthma.

Animals↗
PubMedDate not supplied

Characterization of endothelin receptor subtypes on airway smooth muscle cells.

Endothelin-1 (ET-1) has constrictor and mitogenic effects on airway smooth muscle strips and cultured cells, respectively. This study addresses the type of the ET receptor subtype(s) present on ovine airway smooth muscle cells and the possibility of autocrine effects. The expression of the preproendothelin-1 gene was demonstrated by Northern analysis, and the medium obtained from these cells contained immunoreactive-ET-1. Competitive binding experiments between [125I]ET-1 and ET-1, ET-3, and two ET-receptor subtype selective-ligands, BQ-123 (ETA) and sarafotoxin S6c (ETB), yielded IC50 values of 1.1 +/- 0.1, 227 +/- 13, 12 +/- 1, and 194 +/- 21 nM, respectively. ET-3 also gave a limited number of higher affinity sites. In the presence of BQ-123 (1 microM), the binding of [125I]ET-1 was decreased by 80-85%, and the IC50 values with ET-1, ET-3, and S6c were 2.0 +/- 0.4, 3.6 +/- 0.6, and 1.1 +/- 0.9 nM, respectively. In similar experiments with 0.1 microM sarafotoxin S6c, the respective IC50 values for ET-1 and ET-3 were 2.4 +/- 0.4 and 300 +/- 20 nM. These results demonstrate that about 85 +/- 5% of ET-1 binding to airway smooth muscle cells is to ETA receptors and that these cells produce ET-1 in vitro.

Animals↗
PubMedDate not supplied

Mucociliary transport in central and intermediate size airways: effect of aminophyllin.

Mucociliary transport and the percentage of ciliated cells were studied in large and intermediate sized airways (generations 0-3) of anesthetized mongrel dogs before and after aminophyllin administration. The mean percentage of ciliated cells decreased respectively from 22.0% and 25.4% in the trachea and main bronchi to 8.0% in the lobar and 2.7% in the segmental bronchi. The fastest mean mucous velocity was found in the trachea (4.9 mm/min, S.E. 1.0). Mucous velocity decreased 38% from the trachea to the main bronchi, 55% to the lobar bronchi, and 66% to the segmental bronchi. A positive correlation (r = 0.75) was demonstrated between mucous velocity and the percentage of ciliated cells. After aminophyllin administration, mucous velocity increased 59% in the trachea and 27% in the main bronchi. No statistical difference in mucous velocity could be demonstrated in the smaller airways after aminophyllin, probably due to relative insensitivity of the method in short bronchi with low mucous velocities.

Aminophylline↗
PubMedDate not supplied

Differential effects of leukotrienes C4, D4, and E4 in the pulmonary and systemic vasculature of sheep.

We investigated the comparative direct and cyclooxygenase-mediated effects of the constituents of slow-reacting substance of anaphylaxis (SRS-A), i.e., leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4) on pulmonary and systemic haemodynamics of sheep. In 20 conscious sheep, measurements of pulmonary vascular resistance (Rpv) and systemic vascular resistance (Rsv) were obtained before and after a rapid intravenous injection of LTC4 (0.1 micrograms X kg-1), LTD4 (0.1 micrograms X kg-1) and LTE4 (1 microgram X kg-1). The same protocol was carried out after pretreatment with the leukotriene antagonist FPL-57231 or the cyclooxygenase inhibitor indomethacin. LTD4 increased mean Rpv to 421% of baseline (p less than 0.001) and had a biphasic effect on mean Rsv, which, following an initial decrease of 18% (p less than 0.05), increased to 143% of baseline (p less than 0.05). LTC4 and LTE4 had no significant effects on Rpv, while they increased mean Rsv to 144% and 143% of baseline, respectively (p less than 0.05). This effect was not preceded by a decrease in Rsv. FPL-57231 completely blocked the effects of LTC4, LTD4 and LTE4 on Rsv, and of LTD4 on Rpv. Indomethacin had no effect on LTC4, LTD4 and LTE4-induced increases in mean Rsv, while it prevented the LTD4-induced initial decrease in mean Rsv. Indomethacin also prevented the LTD4-induced increase in Rpv. A dose-response curve (0.05, 0.1, 0.5 and 1 microgram X kg-1) demonstrated that in raising Rsv, LTE4 was approximately 10 times less potent than LTC4 and LTD4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Effect of atropine on tracheal mucociliary clearance and bacterial counts.

The purpose of this study was to determine if atropine, which has been shown to alter mucosal function, prolongs the persistence of inhaled bacteria in the trachea. In conscious sheep, bacterial counts in the trachea were determined by quantitative sterile brush cultures obtained before and serially after a controlled inhalation challenge with an aerosolized solution containing P. hemolytica (10(8) CFU X ml-1). The same animals were studied on two days, once without (control day) and once before and during intramuscular administration of 0.2 mg X kg-1 atropine sulfate at hourly intervals for up to 10 h (atropine day). On the control and atropine days, bacterial counts were zero before, and between 5 X 10(5) and 1.6 X 10(7) CFU X ml-1 immediately after inhalation of P. hemolytica. During the first 2 h after challenge, there was a similar semilogarithmic decline in bacterial counts on the control and atropine days despite the fact that mean tracheal mucociliary transport velocity remained unchanged on the control day, and ranged between 32% and 62% of baseline (p less than 0.05) during the 6-10 h post-drug observation period on the atropine day. However, the time to achieve sterility on the control day was less than or equal to 8 h in all animals, and greater than or equal to 8 h on the atropine day. We conclude that atropine prolongs the persistence of viable bacteria in the trachea. This effect of atropine may be related to an impairment of mucociliary clearance or to other alterations in mucosal function.

Aerosols↗
PubMedDate not supplied

A micro double capillary method for rheologic measurements of lower airway secretions.

We modified the double capillary method of Philipoff et al. [23] to allow rheologic measurements of lower respiratory secretions. The system consists of a precision bore stainless steel capillary (0.58 mm i.d., 5 mm length), a glass capillary (0.92 mm i.d., 15 mm length) and a sample holding tube (1.5 mm i.d., 15 mm length). This series of capillaries is connected to a long polyethylene catheter which permits advancing the system through the inner channel of a fiberoptic bronchoscope, and the placing of the sample holding tube into the lower airways for the aspiration of secretions under direct vision. The required sample volume is 20 microliter. The capillary is then removed from the fiberoptic bronchoscope and placed on a microscope stage; the movement of the meniscus of the sample under an applied vacuum as well as the elastic recoil of the sample after release of the vacuum are measured at body temperature. From this procedure, apparent viscosity (na) and shear elastic modulus (G) are calculated. The accuracy of the method was verified in vitro by using standard viscosity oils and a polymer solution of known elasticity. In five normal conscious sheep, na ranged between 200-3000 poises (shear rate: 0.06-1.0 s-1) and G between 17-83 dyn X cm-2. The micro double capillary method was found adequate for direct rheologic measurements of lower airway secretions.

Animals↗
PubMedDate not supplied

Peripheral airway function in antigen-induced bronchoconstriction.

The density dependence of the maximum expiratory flow-volume curve, functional residual capacity (FRC) and specific airway conductance (SGaw) were studied in 16 asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma, before and during bronchial provocation with ragweed extract (dose-response curve), and following inhalation of isoetharine. In ten of these subjects (seven "reactors" and three "non-reactors"), the baseline volume of isoflow (VisoV) was found to be greater than 20% of forced vital capacity. During antigen challenge, VisoV increased in all subjects; ten of these showed a greater than 35% decrease in SGaw (mean 45%) while the remaining six showed a decrease in SGaw of less than 20% (mean 9%), suggesting central and peripheral airway constriction in the former ("reactors") and primarily peripheral airway constriction in the latter ("non-reactors"). The beta-adrenergic agonist isoetharine increased SGaw and decreased VisoV, suggesting dilation of both central and peripheral airways. We conclude that in asymptomatic subjects with asthma and ragweed hypersensitivity a) peripheral airway dysfunction is frequently present, b) during antigen challenge VisoV may be a more sensitive indicator of airway response than SGaw, and c) the beta-adrenergic agonist isoetharine exhibits its bronchodilator effect in both central and peripheral airways following antigen challenge.

Adult↗