Biomedical subjects

K E Willet

Publications and source records attributed to K E Willet.

23 records · Page 2Linked to original sources

PubMed1990

The role of epithelium in the responsiveness of the bronchi to stimuli.

Airway narrowing in response to different modes of stimuli was measured using a perfused bronchial segment. Acetylcholine, carbachol, histamine, high [K+] and vanadate perfused through the lumen gave small responses as shown by the reduction in flow, but fully constricted the airway when applied to the outside. ACh was 29 times more sensitive on the outside. When the epithelium was removed airway narrowing by these stimuli was increased to equal that on the outside. It was concluded that the role of the epithelia as a barrier is all important. Evidence for an EpDIF released by the epithelium could not be obtained.

Acetylcholine↗

PubMed1990

Airway diameter determines flow-resistance and sensitivity to contractile mediators in perfused bronchial segments.

To study airway reactivity, flow-resistance to carbachol and histamine was measured in perfused bronchial segments. Small-bore airways were more sensitive, flow was reduced to zero and resistance rose very steeply due to mucosal folding while in large-bore airways maximum flow reduction was 50% and resistance increased sigmoidly. Thus the internal diameter of an airway is a crucial determinant of narrowing.

Airway Resistance↗

PubMed1989

Perfused bronchial segment and bronchial strip: narrowing vs. isometric force by mediators.

When bronchial segments were perfused with Krebs solution at a constant pressure (5-6 cmH2O), the resistance rose exponentially with increasing concentrations of either carbachol or histamine in the lumen. The pressure-flow relationship was linear. Histamine and carbachol caused 43 and 47% muscle shortening, respectively, and produced the same maximum effect (Emax) because they both stopped perfusion. In bronchial strips the maximum isometric force or isotonic shortening to carbachol was more than twice that of histamine and the responses showed a plateau. There were no significant differences in sensitivities [negative log of the concentration producing half-maximal response (EC50)] to either carbachol or histamine in the strips (isotonic and isometric) and the segments perfused at constant pressure. When airway segments were perfused at a constant flow, however, responses plateaued and the sensitivities to carbachol and histamine were reduced more than tenfold compared with the strips [4.71 +/- 0.20 and 6.22 +/- 0.08 (SE) for carbachol in segments and isometric strips, respectively, and 3.92 +/- 0.13 and 4.94 +/- 0.11 (SE) for histamine]. We conclude that when segments are perfused at a constant pressure, airway closure occurs before maximal pharmacological activation, as seen in airway strips.

Airway Resistance↗

PubMed1988

Effect of elastase instilled into the trachea on airways mechanics in guinea pigs.

Instilled elastase caused an inflammatory response in the lungs of guinea pigs which was observed at 6 h, 24 h, and 48 h post-treatment. The inflammation was most marked at 24 h and was characterised by a loss of epithelial cilia and detachment of epithelial cells from the basement membrane, a marked increase in polymorphonuclear leukocytes (PMNs) in blood vessels of the tracheal submucosa and an infiltration of macrophages into the parenchyma. Compared with controls, isolated tracheal preparations from 24 h and 48 h elastase pretreated animals were hyperreactive (Emax) to histamine and carbachol. This hyperreactivity persisted in tracheas from 48 h elastase pretreated animals after removal of the epithelial layer. Parenchymal strips were hyperreactive to histamine only. Tissue sensitivity (EC50) was little affected by elastase. Tracheal preparations incubated in 0.01% elastase for 3 h responded normally. In vivo responses of Raw and Cdyn to histamine were unaffected by elastase at 24 h and 48 h. However, the slope of the dose-response curve to acetylcholine was steepened 24 h after elastase instillation, but not at 48 h. In contrast to other models of inflammation elastase evokes in vitro but not in vivo hyperresponsiveness.

Animals↗

PubMedDate not supplied

Pirenzepine blunts the pulmonary parenchymal response to inhaled methacholine.

To determine the role of M1 muscarinic receptors in the response of the pulmonary parenchyma to inhaled methacholine (MCh), 20 mongrel, out-bred puppies, 8-10 weeks of age were challenged following pretreatment with either saline (control), UH-AH37 (a combined M1 & M3 receptor blocker), or pirenzepine (a relatively selective M1 receptor blocker). In addition, eight fox hound-beagle puppies, born and raised in a clean animal house, were studied. Relatively selective doses of pirenzepine produced a dose-dependent shift to the right of the parenchymal dose-response curves (P = 0.031), with no effect on the airway dose-response curve (P = 0.102). The fox hound-beagle puppies showed less parenchymal response (P <0.0005), but equivalent airway response (P = 0.468), to MCh compared with the mongrel puppies. High doses of pirenzepine (10 000 mu g/kg) and UH-AH37 (3 mg/kg) markedly inhibited both the parenchymal and airway responses to MCh. Data from the present study demonstrate that: (1) while both the airway and pulmonary parenchyma respond to inhaled MCh, the mechanisms by which they respond differ; (2) stimulation of M1 subtype muscarinic receptors are responsible, at least partly, for the parenchymal response; and (3) experimental conditions, such as the breed and housing conditions of animals, may have major influences on the parenchymal response to inhalational challenge tests.

Animals↗