Effects of halothane on mucociliary activity in vivo.

The effect of halothane on mucociliary activity in the rabbit maxillary sinus in vivo was recorded photoelectrically. Administration of halothane (1%, 2% or 4%) into the maxillary sinus induced a temporary acceleration of mucociliary activity. The peak increase (39.1% +/- 9.1%, p < 0.05, n = 5) was seen after the 4% concentration. Long-term exposure (60 minutes) of the maxillary sinus to halothane (2%) first induced an increase of 28.4% +/- 4.6% (p < 0.05, n = 6), lasting approximately four minutes, and followed after about 15 minutes by a decrease of mucociliary activity. The maximum decrease during the 60-minute period was 19.6% +/- 2.8% (p < 0.05, n = 6). Mucociliary activity returned to its baseline level approximately 25 minutes after withdrawal of halothane. Halothane delivered to the rabbit through a tracheal cannula at 1.1% for 60 minutes did not impair mucociliary activity in the maxillary sinus. On the contrary, it initially stimulated mucociliary activity, 19.9% +/- 2.7% (p < 0.05, n = 5). There was also an initial increase in respiratory rate from 62 +/- 7.3 to 89 +/- 12.9 breaths per minute (p < 0.05), which was noticeable after approximately 10 seconds and lasted 4 to 5 minutes. The dose-dependent increase in mucociliary activity seen after short-term exposure to halothane is probably due to stimulation of afferent C fibers, because halothane may be considered an airway irritant. The reversible depressant effect seen after 15 minutes of exposure is in accordance with findings in previous studies in vitro. The mechanism by which halothane impairs mucociliary activity is at present not known. However, halothane administered to the lower airways does not impair mucociliary activity in the maxillary sinus, indicating that halothane affects the ciliated epithelium directly and that the state of anesthesia itself has no effect on mucociliary activity.

Cyclic adenosine monophosphate stimulation of mucociliary activity in the upper airways in vivo.

Xanthine derivatives are known to accelerate mucociliary transport in the lower airways, probably by preventing degradation of cyclic adenosine monophosphate (cAMP) and thereby increasing its intracellular concentration. The purpose of this study was to investigate the effects of cAMP on mucociliary activity in the upper airways. The effect on the mucociliary activity in the rabbit maxillary sinus of the xanthine derivatives theophylline and enprophylline was compared to that of the cAMP analog dibutyryl cAMP. The compounds were administered into the maxillary artery, and the response was recorded with a photoelectric technique. Infusions of theophylline (1.0 and 10 mg/kg) increased mucociliary activity (22.8% +/- 5.9%, n = 6, and 21.6% +/- 4.9%, n = 7, p < .05, respectively). Infusions of enprophylline (1.0 and 10.0 mg/kg) accelerated mucociliary activity (at the highest dosage tested, 24.3% +/- 4.1%). Infusions of dibutyryl cAMP (0.1 and 1.0 mg/kg) stimulated mucociliary activity, with the maximum increase (20.1% +/- 3.0%, n = 13, p < .05) being observed at a dosage of 0.1 mg/kg. The infused substances increased mucociliary activity within 1 minute after the start of the infusion, the duration of the response being approximately 20 minutes for theophylline, 22 minutes for enprophylline, and 12 minutes for dibutyryl cAMP. The present results support the view that cAMP is involved in regulating mucociliary activity in the upper airways. It remains to be elucidated whether xanthines such as theophylline and enprophylline are beneficial in upper airway disease in which mucociliary function is impaired (eg, chronic sinusitis).

Hyaluronic acid in middle ear surgery.

The efficacy of hyaluronic acid when utilized in tympanoplasty was investigated in a multicenter, randomized, prospective patient blinded study. Of the 117 patients who completed the study, a majority (76) were treated with myringoplasty, 26 with myringoplasty combined with ossiculoplasty, and 15 with ossiculoplasty alone. The patients were evaluated by the operating surgeon up to 3 months following surgery, when the final assessment was made. The patients were divided into three groups: group 1 was treated with hyaluronic acid, 1 percent; group 2 with hyaluronic acid, 1.9 percent; and group 3 constituted the control where no hyaluronic acid was used at all. In the two test groups, utilizing hyaluronic acid, no gelatinous sponge was allowed to be left in the middle ear after surgery, whereas the control group was operated according to standard principles. The three groups were compared after the termination of the study as regards quality of healing and their hearing results. It could be concluded that the healing process within the middle ear and the tympanic membrane, as well as the hearing ability, was similar in all three groups. Thus no statistically significant differences could be obtained between the patient groups in which hyaluronic acid had been utilized in any concentration and the control group operated according to standard routine. This finding does not exclude, however, that hyaluronic acid might have a place in tympanoplastic surgery of today, since the long-term results were not evaluated here.

The effect of noradrenaline on mucociliary activity in the rabbit maxillary sinus.

The effect of noradrenaline (NA) on mucociliary activity in the rabbit maxillary sinus was investigated in vivo by injecting it at increasing dosages (10(-11) to 10(-4) mol/kg) into the maxillary artery, the mucociliary response being recorded photoelectrically. NA increased mucociliary activity at a dosage of 10(-5) mol/kg, the maximal increase being 16.1 +/- 2.6%. The NA-induced stimulation of mucociliary activity had a latency of 20 s, and the activity returned to base-line level within 3 min. Pretreatment with the alpha-antagonist phentolamine (0.2 and 1.0 mg/kg) or the cholinergic antagonist atropine (1 mg/kg) did not alter mucociliary response to NA. Blockade with the beta-antagonist propranolol did not significantly reduce the maximal response to NA, which was 16.1 +/- 2.6% before and 11.1 +/- 3.0% after pretreatment with propranolol (n = 7; p = 0.2). In contrast, pretreatment with the prostaglandin-synthesis inhibitor indomethacin reduced the response from 12.9 +/- 2.9% to 6.3 +/- 1.3% (n = 6; p < 0.05), suggesting that at high dosages NA stimulates mucociliary activity via the cyclo-oxygenase pathway.

Neuropeptide Y in the rabbit maxillary sinus modulates cholinergic acceleration of mucociliary activity.

The distribution of neuropeptide Y (NPY)-immunoreactivity was investigated in the rabbit maxillary sinus and adjacent ganglia. A moderate supply of NPY-containing nerve fibers occurred around seromucous glands and a denser supply around small blood vessels. Only a few immunoreactive nerve fibers were seen beneath the epithelium. Double immunostaining showed that vasoactive intestinal peptide (VIP) coexisted with NPY in the nerve fibers surrounding blood vessels and seromucous glands. NPY-containing nerve cell bodies were numerous in the superior cervical ganglion, and moderately numerous in the sphenopalatine ganglion. The finding of NPY-containing neurons in the latter parasympathetic ganglion suggests that NPY may influence the cholinergic regulation of mucociliary activity. The effect of NPY on the mucociliary activity of the maxillary sinus in connection with cholinergic stimulation has therefore been investigated in vivo using a photoelectric technique. At dosages of 2.5 and 5.0 micrograms/kg, the ganglionic stimulant nicotine bitartrate, which increases mucociliary activity by a cholinergic pathway, accelerated mucociliary activity by 28.0 +/- 7.5% and 36.8 +/- 6.2%, respectively. In the same experiment repeated during infusion of NPY (0.1 microgram/kg/min), the increase in mucociliary activity was reduced to 10.8 +/- 2.3% and 28.9 +/- 7.1%, respectively. Infusion of NPY did not affect the stimulating effect on mucociliary activity by bolus injections (0.1 and 0.5 microgram/kg) of the cholinergic agonist, methacholine. It is concluded that NPY-like immunoreactivity is present in nerve fibers in the rabbit maxillary sinus and in neurons in the sympathetic and parasympathetic ganglia that supply the nose and paranasal sinuses. NPY attenuates the effect of nicotine on mucociliary activity, probably via a prejunctional mechanism, and may act as a modulator of cholinergic regulation of the mucociliary system.

Sympathetic nerve stimulation influences mucociliary activity in the rabbit maxillary sinus.

The effect of preganglionic sympathetic nerve stimulation on mucociliary activity in the rabbit maxillary sinus was investigated in vivo. Response to nerve stimulation was recorded photoelectrically and expressed as a percentage of the basal mucociliary activity prior to stimulation. Nerve stimulation (15 V, 5 ms) for 60 s at 2, 10 and 20 Hz stimulated mucociliary activity, the maximum increase being 21.1 +/- 1.3% at 20 Hz, an increase that pretreatment with the cholinergic antagonist atropine reduced to 14.5 +/- 2.4%, suggesting that part of the response involves cholinergic mechanisms. Nerve stimulation (10 Hz) of animals pretreated with the beta-adrenoceptor antagonist propranolol reversed the mucociliary response from an increase to a decrease (-10.6 +/- 1.6%), indicating the involvement of beta-receptors in the nerve-evoked increase. Pretreatment with the alpha-adrenoceptor antagonist phentolamine had no effect on response to nerve stimulation. Rabbits given a combined atropine, propranolol and phentolamine blockade manifested decreased mucociliary activity in response to nerve stimulation (-10.6 +/- 2.1%). Guanethidine pretreatment blocked the effect of nerve stimulation on mucociliary activity, including the observed decrease after combined blockade, indicating the effect to be mediated via sympathetic nerve fibres. The decrease in mucociliary activity in response to nerve stimulation after combined cholinergic-, beta-, and alpha-adrenoceptor blockade suggests the presence of a nonadrenergic, non-cholinergic inhibitory mechanism. It is possible that this effect is mediated by release of neuropeptide Y, as intraarterial injections of neuropeptide Y reduce mucociliary activity in the rabbit maxillary sinus, and as neuropeptide Y is released in the upper airways upon sympathetic nerve stimulation.

The effect of neuropeptide Y on mucociliary activity in the rabbit maxillary sinus.

The effect of neuropeptide Y (NPY) on mucociliary activity in the rabbit maxillary sinus was investigated in vivo by injecting NPY at increasing dosages into the maxillary artery, response being recorded photoelectrically. At dosages of 0.1-5.0 micrograms/kg, NPY reduced mucociliary activity dose-dependently, the maximum decrease being 14.6 +/- 1.8%, at a dosage of 5.0 micrograms/kg. The NPY-induced reduction of the mucociliary activity manifested brief latency, the peak effect occurring within 3 min followed by a slow return to the baseline value 4-9 min after injection. The response of mucociliary activity to NPY remained unaffected by pretreatment with the alpha-adrenergic antagonists yohimbine (alpha 2) at 100.0 micrograms/kg and phentolamine (alpha 1 + alpha 2) at 0.2-1.0 mg/kg, indicating that the effect of NPY is not mediated via alpha-receptors. Pretreatment with the calcium antagonist nifedipine at 100.0 micrograms/kg inhibited the effect of NPY, suggesting that the NPY-induced decrease may be calcium dependent.

Histamine stimulation of mucociliary activity in the rabbit maxillary sinus.

The in vivo effect of histamine on mucociliary activity in the rabbit maxillary sinus was investigated by injecting histamine into the maxillary artery and recording the responses with a photoelectric technique. Histamine stimulated the mucociliary activity dose-dependently in the dose range 10 to 1,000 micrograms/kg. The maximum response was 31.6% +/- 3.7% at a dose of 50 micrograms/kg. The histamine-induced stimulation of the mucociliary activity was characterized by a short latency with a peak response within 1 to 2 minutes and a slow decline lasting about 5 minutes. The response displayed tachyphylaxis. Cholinergic blockade with atropine did not affect the response to histamine. Blockade of H1 receptors with pyrilamine abolished the response to histamine, whereas blockade of H2 receptors with cimetidine was without effect. The H2 agonist dimaprit failed to stimulate the mucociliary activity. It is concluded that histamine stimulates the mucociliary activity in the rabbit maxillary sinus via H1 receptors.

Mucociliary activity and the diving reflex.

It has previously been shown that mucociliary activity in the rabbit maxillary sinus is immediately increased after short-term exposure to such airway irritants as cigarette smoke and ammonia vapor. This increase is mediated through the stimulation of capsaicin-sensitive nerve endings. Besides producing the mucociliary effect, these irritants inhibit breathing, a response characteristic of the diving reflex in mammals. Whether an increase in mucociliary activity is part of the diving reflex was investigated by injecting 0.5 mL water into the nasopharynges of anesthetized rabbits. Mucociliary and respiratory responses were compared with the effects of mechanical stimulation (ie, rotating an intranasal catheter until sneezing occurred). Water challenge produced an increase in mucociliary activity of 21.6% +/- 2.4%, a response that began approximately 10 seconds after injection. Mucociliary acceleration was completely blocked by atropine, indicating a cholinergic mechanism, but was unaffected by pretreatment with capsaicin. The respiration rate was inhibited by about 45% after challenge with water. Pretreatment with atropine and capsaicin had no effect on this reduced respiratory rate. Mechanical stimulation of the nasal mucosa accelerated mucociliary activity. This response appeared approximately 4 seconds after stimulation was begun, and occurred simultaneously with the onset of sneezing. The peak increase was 22.0% +/- 2.1%. Sneezing was followed by an increase in the respiration rate of about 40%. Pretreatment with atropine or capsaicin had no effect on respiratory responses, but did inhibit mucociliary acceleration, suggesting that the response is mediated through cholinergic effector neurons after activation of capsaicin-sensitive nerve endings.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of leukotrienes and platelet activating factor on mucociliary activity in the rabbit maxillary sinus.

Inflammatory mediators released in the airways during allergic reactions can affect the mucociliary system. Leukotrienes and platelet activating factor have been shown to affect the mucociliary activity in various cell preparations. The in vivo effects of these inflammatory mediators on mucociliary activity in rabbit maxillary sinus were investigated using a photoelectric technique. Leukotrienes C4 and D4 in the dose range 0.01-10.0 nmol/kg did not alter mucociliary activity significantly, either when given as bolus injections or as intraarterial infusions. Platelet activating factor had no effect in the dose range 0.001-0.1 nmol/kg. A dose of 1.0 nmol/kg increased mucociliary activity by 20.2 +/- 5.5% but produced adverse respiratory and circulatory effects at the same time. It is concluded that the inflammatory mediators leukotrienes C4, D4 and platelet activating factor have no essential regulatory influence on mucociliary activity in the upper airways of the rabbit.

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.

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.

Growth potential of acoustic neuromas.

Tumor samples from 32 patients with acoustic neuroma operated with translabyrinthine approach were analyzed with flow cytometric technique with respect to ploidy and cell cycle phase distribution. In all cases the diagnosis of acoustic neuroma was verified histologically, two patients had Recklinghausen's disease. None of the tumors showed aneuploid cell lines. Median S-phase fraction was 6.8% (range 1.4 to 19.9%). The spread of S-phase values had a greater range for the smaller tumors (volume less than or equal to 2 cm3) of the material. There was no correlation neither between the fraction of cells in S-phase and age of the patient, nor between the fraction of cells in S-phase and tumor size. The present finding with a great variability in S-phase values does not support an expectant attitude regarding surgical intervention in patients with acoustic neuromas.

VIP potentiates cholinergic effects on the mucociliary system in the maxillary sinus.

The neuropeptide vasoactive intestinal polypeptide (VIP), which is found in a population of cholinergic parasympathetic neurons in the airways, has no effects per se on mucociliary activity. In order to test the hypothesis that VIP may modulate cholinergic regulation of the mucociliary system, VIP was infused intraarterially (8.4 pmol/kg/min), and the response to challenges with methacholine in the maxillary sinus of rabbits were recorded with a photoelectric technique. Occurrence of VIP-like immunoreactivity in the rabbit maxillary sinus, maxillary nerve, and sphenopalatine ganglion was investigated. Immunoreactivity against VIP was found in nerve fibers in the subepithelial layer of the maxillary sinus and in numerous nerve cell bodies in the sphenopalatine ganglion. Infusion of VIP potentiated the mucociliary increase induced by methacholine. The mucociliary wave frequency change increased from 6.1% +/- 1.7% to 13.3% +/- 3.9% (0.01 micrograms/kg methacholine), from 11.6% +/- 3.6% to 18.8% +/- 2.2% (0.05 micrograms/kg) and from 17.0% +/- 3.0% to 27.4% +/- 3.6% (0.1 micrograms/kg). Both peak responses and response durations increased during infusions. In contrast, the vasodilating agent papaverine sulphate did not influence the mucociliary response to methacholine. The modulating effect of VIP on the mucociliary system, taken together with the morphologic observations, suggest that VIP may have a physiologic role in the regulation of the mucociliary system in the maxillary sinus.

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.

Translabyrinthine acoustic neuroma surgery as performed by the otoneurosurgical group at Lund University Hospital.

The Lund otoneurosurgical group has operated 97 out of 118 pontine angle tumours using the translabyrinthine approach originally described by House. The pre- and postoperative evaluation of these 97 patients is described. The traditional classification of acoustic neuromas, the results of the reported surgery and complications are discussed.

The cholesteatomatous ear one year after surgery with obliteration technique.

Fifty-seven patients with middle ear cholesteatoma were treated surgically by eradicating the cholesteatoma after a canal wall-down procedure had been performed. During the same session the canal wall was rebuilt with autologous bone, the tympanic membrane repaired with fascia, and the mastoid cavity and epitympanic space obliterated with autologous cortical mastoid bone chips and a retroauricular, anteriorly based muscle flap. One year later a second look procedure was performed in all the patients (N = 57), which permitted the anatomic effects of the obliteration operation to be mapped out before ossicular reconstruction was undertaken. At three, six, and twelve months after the first operation any secretion from the ear was recorded. Recurrent cholesteatoma was not found in any single case, residual cholesteatoma in only three cases (5.3%). The tympanic membrane was intact in fifty-four cases (94.7%) and perforated in three, none of which was combined with a residual cholesteatoma. Even though twenty-four of the fifty-seven cases had a secreting ear before the eradicating operation, fifty-six (98.2%) stayed dry during the year of observation between the two operations. Therefore, with very few exceptions, a dry, cholesteatoma-free ear and an intact tympanic membrane may be expected one year postoperatively in patients with middle ear cholesteatoma surgically treated using the described obliteration technique.

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.