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Biomedical subjects

U Mercke

Publications and source records attributed to U Mercke.

At least 55 records · Page 3Linked to original sources

The influence of varying air humidity on mucociliary activity.

The influence of varying humidity levels in the air surrounding the mucous membrane of rabbit tracheae has been investigated in vitro at 34 degrees C, 37 degrees C and 40 degrees C. The following results were obtained: (1) The average mucociliary wave frequency was linearly reduced following decreasing levels of relative humidity (r.h.) from 90% to 20%. (2) A temperature of 40 degrees C was more detrimental to the mucociliary function than that of 34 degrees C and 37 degrees C (body temperature) at decreasing levels of r.h. (3) At decreasing levels of r.h. the duration of experiments with preservation in recordable activity ("mucociliary survival time") was significantly shorter (p smaller than 0.05) between 50% and 40% r.h. than between 60% and 50% r.h.

Air↗

Mucociliary wave pattern. A comparative analysis of extracellular and intracellular activities.

Experimental in vitro studies have been made on the intracellular electrical activity and the extracellular wave movements of ciliary cells in rabbit trachea. The following results were obtained: 1. Surface light reflections from the mucous layer and from the ends of moving cilia showed about the same frequency and amplitude pattern as the intracellular action potential oscillations at 40 degrees C and 50 degrees C. At lower temperatures, however, there was a considerable discrepancy between them. 2. Surface light reflections from mucociliary wave movements had the same frequency in two areas 20 mum apart, but amplitude variations were out of phase. 3. Intracellular oscillations with a frequency of 18-21 per sec and a maximum amplitude of 1 mV have been recorded. Amplitude variations indicating rhythmical frequency variations have also been recorded. 4. The mean frequency of the intracellular action potential oscillations showed no remarkable differences at 20 degrees C, 30 degrees C, 40 degrees C and 50 degrees C.

Action Potentials↗

The mucociliary activity of the upper respiratory tract. I. A method for use in experimental studies on human material.

A method for standardized recordings of the mucociliary activity of the mucosa in the human respiratory tract is described. Nasal polyps, adenoid vegetations and biopsy material from maxillary sinuses have been used for preliminary in vitro experiments. The dependence of the mucociliary activity on oxygen supply from the surrounding air is emphasized. The influence of varying gas mixtures on the mucociliary activity can be thoroughly studied. The method is also applicable for in vivo recordings in the operating theatre during Luc Caldwell operations. A combination of in vivo and in vitro studies is under way in order to elucidate the aetiology, treatment, and prognosis of diseases of the upper respiratory tract.

Adenoids↗

Effects of sympathomimetic agonists and antagonists on mucociliary activity.

The effect on the mucociliary (m.c.) wave frequency of sympathomimetic agonists and antagonists was studied in the maxillary sinus in anesthetized rabbits. The non-selective beta-adrenoceptor agonist isoprenaline (0.005-10 micrograms/kg i.a.) and the selective beta2-adrenoceptor agonist salbutamol (0.01-10 micrograms/kg, i.a.) induced a dose-dependent acceleration of the m.c. wave frequency, whereas the beta1-adrenoceptor agonist prenalterol (1-200 micrograms/kg, i.a.) did not influence the basal m.c. activity. The selective alpha1-adrenoceptor agonist phenylephrine (0.01-20 micrograms/kg, i.a.) and the selective alpha2-adrenoceptor agonist oxymetazoline (0.001-1 microgram/kg, i.a.) both induced a dose-dependent retardation of the m.c. wave frequency. The non-selective beta-adrenoceptor antagonist propranolol (2-200 micrograms/kg, i.a., and 1 mg/kg, i.v.) and the non-selective alpha-adrenoceptor antagonist phentolamine (0.1-1 000 micrograms/kg, i.a.) had no influence on the basal m.c. wave frequency. Propranolol (1-2 mg/kg, i.v.) reduced the effect of isoprenaline and salbutamol (both in the dose range of 0.01-10 micrograms/kg, i.a.) and similarly phentolamine (0.2 and 1 mg/kg, i.a.) reduced the effect of oxymetazoline (0.01-10 microgram/kg, i.a.). It was concluded that during basal conditions in the anesthetized rabbit the m.c. activity functions independently of sympathetic activity and that sympathomimetic agonists acting on beta2-adrenoceptors accelerate the wave frequency, whereas sympathomimetic agonists acting on alpha1 and alpha2-adrenoceptors have a retarding effect, all in a dose-dependent manner.

Albuterol↗

A method for evaluating the effect of pharmacological substances on mucociliary activity in vivo.

A test model for in vivo studies of the effect of pharmacological substances on mucociliary activity in the rabbit maxillary sinus is presented. The method permits administration of pharmacological substances and recording of the mucociliary activity under conditions that mimic the physiological situation very closely. The test substances are given intra-arterially. Using a photoelectric technique the mucociliary activity is recorded from a small and limited area of the mucous membrane. There is minimal exposure to external stimuli since normal sinus ventilation is retained. Various factors which may influence the results, e.g. the anesthesia, movements from cardiac and respiratory activity, and the volumes and injection velocities of test doses, are analysed and discussed. When the animal model was tested with serotonin, ATP, and certain cholinergic and adrenergic agents, it was found to be reliable. It permitted easy detection of changes in the mucociliary activity and gave reproducible results.

Animals↗

Effects of the parasympathomimetic drug methacholine and its antagonist atropine on mucociliary activity.

The effect on the mucociliary (m.c.) activity of the parasympathomimetic drug methacholine and its antagonist atropine was studied with the aid of a newly developed animal test model, designed for evaluating the effect of pharmacological substances on the m.c. wave frequency. Methacholine i.a. (0.01-2 micrograms/kg) was found to give a dose-dependent acceleration of the m.c. wave frequency, and the threshold dose 0.03 +/- 0.02 (+/- S.D.) micrograms/kg is suggested to be within physiological limits. The anticholinergic drug atropine i.a. (0.05-0.5 mg/kg) did not influence the basal m.c. wave frequency, but a dose of 0.2 mg/kg reduced or abolished the responses to methacholine (0.05-2 micrograms/kg). These results indicate that the basal m.c. activity functions independently of parasympathetic activity in anesthetized animals, that parasympathomimetic drugs influence the m.c. activity and that the effects of these drugs can be reduced or blocked by atropine.

Animals↗

Bradykinin accelerates mucociliary activity in rabbit maxillary sinus.

The in vivo effect of bradykinin on mucociliary (m.c.) activity in the rabbit maxillary sinus was investigated by administering the substance (0.01-10.0 micrograms/kg) via arteria maxillaris and recording the responses with a non-invasive photoelectric technique. Bradykinin accelerated the m.c. activity in a dose-dependent manner in the dose range 0.05-10.0 micrograms/kg. While the action of bradykinin was resistant to pretreatment with indomethacin 10.0 mg/kg, it was considerably weakened by the substance P antagonist [D-Pro2, D-Trp7,9]SP 1 mg/kg. The initial effect of bradykinin was also suppressed by atropine, suggesting that bradykinin accelerates m.c. activity by a dual mechanism comprising both SP and acetylcholine. Bradykinin probably stimulates a reflex arc in the airways involving afferent SP neurons and efferent post-ganglionic parasympathetic neurons.

Animals↗

Antidromic nerve stimulation accelerates mucociliary activity in rabbit maxillary sinus.

The neuropeptide substance P (SP) is released from unmyelinated C-fibres in sensory nerves by antidromic nerve stimulation. In order to study the effect on mucociliary (m.c.) activity, the isolated distal end of the maxillary nerve was stimulated electrically (8 V, pulse rate 10 Hz, 5 ms pulses) 2-4 min, while the m.c. wave frequency in the maxillary sinus was recorded by a photoelectric technique. The m.c. wave frequency increased during stimulation by 35.4 +/- 4.9% (range 22.0-62.2%). Following pretreatment with atropine the m.c. activity increased by only 20.0 +/- 1.3% (range 14.9-21.9%) indicating that part of the response was mediated via stimulation of muscarinic receptors. The cholinergic part of the response is presumably secondary to release of SP since the SP antagonist [D-Pro2, D-Trp7,9]SP abolished the effect of nerve stimulation. Sympathetic ganglionectomy did not influence the response to antidromic nerve stimulation. It is concluded that antidromic stimulation of the maxillary nerve accelerates m.c. activity through a dual mechanism, involving release of SP, or SP-like peptides, from sensory C-fibre nerve endings as well as release of acetylcholine.

Animals↗

The morphological basis for the effect of substance P on mucociliary activity in rabbit maxillary sinus.

The mucociliary (m.c.) activity in rabbit maxillary sinus is accelerated by the neuropeptide substance P (SP). The morphological basis for this mechanism was investigated by immunocytochemistry using monoclonal antibodies directed against SP. SP-like immunoreactivity was found in nerve fibres in the subepithelial layer of the sinus mucosa, in the maxillary nerve, and in nerve endings close to nerve cell bodies in the sphenopalatine ganglion. Thus, there is morphological evidence in the rabbit that SP plays a role in the regulation of m.c. activity. The results also support the view that the rabbit maxillary sinus is a suitable experimental model for studying SP effects in the airway mucosa.

Animals↗

Nasal exposure to airway irritants triggers a mucociliary defence reflex in the rabbit maxillary sinus.

The effect on mucociliary (m.c.) activity in the rabbit maxillary sinus of cigarette smoke and ammonia (NH3) vapour delivered through a tracheal cannula or as nasal challenges was investigated by a photo-electric technique, and compared with simultaneously induced changes in the respiratory rate. Neither irritant had any effect on m.c. activity in the sinus after tracheo-bronchial exposure. However, the respiration rate was increased by NH3 vapour (2.5 ml, diluted 1:1 with room air) and neat cigarette smoke (10 ml) by 76.9% and 24.3% respectively (median values). In contrast, nasal challenges with both irritants increased m.c. activity by 24.1% (NH3) and 19.1% (cigarette smoke), and reduced the respiration rate by 31.0% (NH3) and 28.4% (cigarette smoke) (median values). NH3 vapour sometimes produced an apnea proper. Identical results were obtained in laryngectomized rabbits, indicating that laryngeal afferents were not involved in the responses. Moreover, topical application of the C-fibre stimulant capsaicin mimicked the effects produced by the airway irritants. It is concluded that nasal exposure to irritants triggers at least two different protective reflexes. One is the increase of m.c. activity in the upper airways involving sensory C-fibres and the other the apneic reflex of Kratschmer.

Ammonia↗

Relations between blood flow and mucociliary activity in the rabbit maxillary sinus.

The effects of two sympathomimetic drugs on mucociliary activity and mucosal blood flow in the rabbit maxillary sinus were investigated by using a photo-electric technique (mucociliary activity) and laser Doppler flowmetry (blood flow). The responses produced were compared with effects of ligation of the external carotid artery. The alpha 1-agonist phenylpropanolamine (0.1-100 micrograms/kg) had no effect on the mucociliary activity, whereas the blood flow was reduced by 33.8 +/- 8.9% (mean +/- SE) when the dose was 100 micrograms/kg. The alpha 2-agonist xylometazoline (0.01-10.0 micrograms/kg) reduced mucociliary wave frequency by 21.6 +/- 4.6% (mean +/- SE) (maximum) for the dose 10 micrograms/kg. The blood flow was reduced by xylometazoline in the interval 1.0 to 10.0 micrograms/kg, with a maximum decrease of 65.8 +/- 2.6% (mean +/- SE) for the dose of 10 micrograms/kg. Ligature of the external carotid artery reduced blood flow by 76.0 +/- 4.6% (mean +/- SE), but did not significantly influence the mucociliary wave frequency. It is concluded that the decrease in mucociliary activity induced by alpha 2-adrenoceptor agonists is not due to a reduced blood flow.

Adrenergic alpha-Agonists↗

The effects of prostaglandins E1, E2 and F2 alpha on mucociliary activity in the rabbit maxillary sinus.

The in vivo effects of prostaglandins E1, E2 and F2 alpha on mucociliary activity in the rabbit maxillary sinus were investigated using a photoelectric technique. Prostaglandins E1 and F2 alpha both accelerated the mucociliary wave frequency in a dose-dependent fashion. For prostaglandin E1 the maximum increase was 17.4 +/- 2.6% (0.1 micrograms/kg), for prostaglandin F2 alpha it was 24.1 +/- 3.0% (10 micrograms/kg). The effects of prostaglandin E2 was inconsistent. Although some doses stimulated mucociliary activity, the effects were not reproducible. Inhibition of phosphodiesterase with theophylline did not alter the response to exogenous prostaglandin E1, nor did inhibition of endogenous prostaglandin synthesis with indomethacin affect the basal mucociliary activity or the response to exogenous prostaglandin E1. The present findings suggest that the tested prostaglandins are of minor importance for regulating mucociliary function in the rabbit maxillary sinus.

Alprostadil↗

Cholinergic and C-fibre mediated mechanisms in the stimulation of mucociliary activity induced by prostaglandins and histamine.

The involvement of cholinergic and C-fibre mediated mechanisms in the stimulation of mucociliary activity induced by prostaglandins and histamine was investigated in vivo in the rabbit maxillary sinus with a photoelectric technique. The prostaglandins E, (PGE,) and F2(2) alpha (PGF2 alpha) in dose of 0.1 microgram/kg and 10 micrograms/kg respectively stimulated the mucociliary activity in a biphasic fashion, with a small initial response during the first 1-2 min and a later maximum response after 3-4 min. These effects were resistant to atropine and to the SP antagonist (D-Pro2, D-Trp7,9)SP. The small initial response was blocked by pretreatment with high doses of capsaicin (13 mg i.a.), while the maximum response was unaffected. This indicates that the mucociliary responses induced by PGE, and PGF2 alpha involve capsaicin-sensitive C-fibres but that neither acetylcholine nor substance P were responsible. Histamine (50 micrograms/kg) stimulated mucociliary activity in the rabbit maxillary sinus and the effect was abolished by pretreatment with high doses of capsaicin and reduced by the SP antagonist (D-Pro2, D-Trp7,9)SP. This indicates that the histamine-induced stimulation of mucociliary activity involves capsaicin-sensitive C-fibres and that the effect might be mediated by substance P.

Alprostadil↗